Clinical Trial: NCT02465060 - My Cancer Genome

NCT02465060

Description:

This phase II MATCH trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.

Related Conditions:

Breast Carcinoma
Lymphoma
Malignant Solid Tumor
Multiple Myeloma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT02465060

Trial Eligibility

Document

Title

Brief Title: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
Official Title: Molecular Analysis for Therapy Choice (MATCH)

Clinical Trial IDs

ORG STUDY ID: NCI-2015-00054
SECONDARY ID: NCI-2015-00054
SECONDARY ID: EAY131
SECONDARY ID: EAY131
SECONDARY ID: EAY131
SECONDARY ID: U10CA180820
SECONDARY ID: U24CA196172
NCT ID: NCT02465060

Conditions

Advanced Malignant Solid Neoplasm
Bladder Carcinoma
Breast Carcinoma
Cervical Carcinoma
Colon Carcinoma
Colorectal Carcinoma
Endometrial Carcinoma
Esophageal Carcinoma
Gastric Carcinoma
Glioma
Head and Neck Carcinoma
Kidney Carcinoma
Liver and Intrahepatic Bile Duct Carcinoma
Lung Carcinoma
Lymphoma
Malignant Uterine Neoplasm
Melanoma
Ovarian Carcinoma
Pancreatic Carcinoma
Plasma Cell Myeloma
Prostate Carcinoma
Rectal Carcinoma
Recurrent Bladder Carcinoma
Recurrent Breast Carcinoma
Recurrent Cervical Carcinoma
Recurrent Colon Carcinoma
Recurrent Colorectal Carcinoma
Recurrent Esophageal Carcinoma
Recurrent Gastric Carcinoma
Recurrent Glioma
Recurrent Head and Neck Carcinoma
Recurrent Liver Carcinoma
Recurrent Lung Carcinoma
Recurrent Lymphoma
Recurrent Malignant Solid Neoplasm
Recurrent Melanoma
Recurrent Ovarian Carcinoma
Recurrent Pancreatic Carcinoma
Recurrent Plasma Cell Myeloma
Recurrent Prostate Carcinoma
Recurrent Rectal Carcinoma
Recurrent Skin Carcinoma
Recurrent Thyroid Gland Carcinoma
Recurrent Uterine Corpus Cancer
Refractory Lymphoma
Refractory Malignant Solid Neoplasm
Refractory Plasma Cell Myeloma
Skin Carcinoma
Thyroid Gland Carcinoma
Uterine Corpus Cancer

Interventions

Drug	Synonyms	Arms
Adavosertib	AZD-1775, AZD1775, MK-1775, MK1775	Subprotocol Z1I (BRCA1 or BRCA2 gene mutation)
Afatinib	BIBW 2992, BIBW2992	Subprotocol A (EGFR activating mutation)
Afatinib Dimaleate	(2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate), BIBW 2992MA2, BIBW2992 MA2, Gilotrif	Subprotocol A (EGFR activating mutation)
Binimetinib	ARRY-162, ARRY-438162, MEK162, Mektovi	Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61)
Capivasertib	AZD5363	Subprotocol Y (Akt mutation)
Copanlisib	BAY 80-6946, PI3K Inhibitor BAY 80-6946	Subprotocol Z1F (PIK3CA mutation)
Copanlisib Hydrochloride	5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2), Aliqopa, BAY 80-6946 Dihydrochloride, BAY-80-6946 Dihydrochloride, Copanlisib Dihydrochloride	Subprotocol Z1F (PIK3CA mutation)
Crizotinib	MET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, Xalkori	Subprotocol C1 (MET amplification)
Dabrafenib	BRAF Inhibitor GSK2118436, GSK-2118436, GSK-2118436A, GSK2118436	Subprotocol H (BRAF V600E/R/K/D mutation)
Dabrafenib Mesylate	Dabrafenib Methanesulfonate, GSK2118436 Methane Sulfonate Salt, GSK2118436B, Tafinlar	Subprotocol H (BRAF V600E/R/K/D mutation)
Dasatinib	BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel	Subprotocol X (DDR2 S768R, I638F, or L239R mutation)
Defactinib		Subprotocol U (NF2 inactivating mutation)
Defactinib Hydrochloride	PF-04554878, VS-6063	Subprotocol U (NF2 inactivating mutation)
Erdafitinib	Balversa, JNJ-42756493	Subprotocol K1 (FGFR amplification)
FGFR Inhibitor AZD4547	AZD4547	Subprotocol W (FGFR pathway aberrations)
Ipatasertib	GDC-0068, RG-7440	Subprotocol Z1K (AKT mutation)
Larotrectinib	ARRY 470, LOXO 101, LOXO-101	Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
Larotrectinib Sulfate	ARRY 470 Sulfate, LOXO 101 Sulfate, LOXO-101 Sulfate, Vitrakvi	Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
Nivolumab	BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo	Subprotocol Z1D (Loss of MLH1 or MSH2 by IHC)
Osimertinib	AZD-9291, AZD9291, Mereletinib, Tagrisso	Subprotocol E (EGFR T790M or rare activating mutation)
Palbociclib	6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991	Subprotocol Z1B (CCND1, 2, or 3 amplification with Rb by IHC)
Pertuzumab	2C4, 2C4 Antibody, HS627, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, Pertuzumab Biosimilar HS627, rhuMAb2C4, RO4368451	Subprotocol J (HER2 amplification >= 7 copy numbers)
PI3K-beta Inhibitor GSK2636771	GSK2636771	Subprotocol N (PTEN mutation or deletion and PTEN expression)
Relatlimab	BMS-986016, BMS986016, Immunoglobulin G4, Anti-(human Lymphocyte Activation Gene-3 Protein) (Human Heavy Chain), Disulfide with Human Light Chain, Dimer	Subprotocol Z1M (LAG-3 expression >= 1%)
Sapanisertib	INK-128, INK128, MLN-0128, MLN0128, TAK-228	Subprotocol L (mTOR mutation)
Sunitinib Malate	SU011248, SU11248, sunitinib, Sutent	Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)
Taselisib	GDC-0032, RO5537381	Subprotocol I (PIK3CA mutation)
Trametinib	GSK1120212, JTP-74057, MEK Inhibitor GSK1120212	Subprotocol H (BRAF V600E/R/K/D mutation)
Trastuzumab	ABP 980, ALT02, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, Herzuma, Kanjinti, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, Ogivri, Ontruzant, PF-05280014, rhuMAb HER2, RO0452317, SB3, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar SB3, Trastuzumab Biosimilar SIBP-01, Trastuzumab-anns, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-pkrb, Trastuzumab-qyyp, Trazimera	Subprotocol J (HER2 amplification >= 7 copy numbers)
Trastuzumab Emtansine	Ado Trastuzumab Emtansine, ADO-Trastuzumab Emtansine, Kadcyla, PRO132365, RO5304020, T-DM1, Trastuzumab-DM1, Trastuzumab-MCC-DM1, Trastuzumab-MCC-DM1 Antibody-Drug Conjugate, Trastuzumab-MCC-DM1 Immunoconjugate	Subprotocol J (HER2 amplification >= 7 copy numbers)
Ulixertinib	BVD-523, VRT752271	Subprotocol Z1L (BRAF fusion, aberration or non-V600 mutation)
Vismodegib	Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449	Subprotocol T (SMO or PTCH1 mutation)

Purpose

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate the proportion of patients with objective response (OR) to targeted study
      agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

      SECONDARY OBJECTIVES:

      I. To evaluate the proportion of patients alive and progression free at 6 months of treatment
      with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple
      myeloma.

      II. To evaluate time until death or disease progression. III. To identify potential
      predictive biomarkers beyond the genomic alteration by which treatment is assigned or
      resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and
      imaging-based assessment platforms.

      IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes
      from pre- through post-therapy imaging can predict objective response and progression free
      survival and to evaluate the association between pre-treatment radiomic phenotypes and
      targeted gene mutation patterns of tumor biopsy specimens.

      OUTLINE:

      STEP 0 (Screening): Patients undergo biopsy along with molecular characterization of the
      biopsy material for specific, pre-defined mutations, amplifications, or translocations of
      interest via tumor sequencing and immunohistochemistry. Consenting patients also undergo
      collection of blood samples for research purposes.

      STEPS 1, 3, 5, 7 (Treatment): Patients are assigned to 1 of 38 treatment subprotocols based
      on molecularly-defined subgroup. (See Arms Section)

      STEPS 2, 4, 6 (Screening): Patients experiencing disease progression on the prior Step
      treatment or who could not tolerate the assigned treatment undergo review of their previous
      biopsy results to determine if another treatment is available or undergo another biopsy.
      Patients may have a maximum of 2 screening biopsies and 2 treatments per biopsy.

      STEP 8 (Optional Research): Consenting patients undergo end-of-treatment biopsy and
      collection of blood samples for research purposes.

      After completion of study treatment, patients are followed up every 3 months for 2 years and
      then every 6 months for 1 year.

Trial Arms

Name	Type	Description	Interventions
Subprotocol A (EGFR activating mutation)	Experimental	Patients with EGFR activating mutation receive afatinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Afatinib Afatinib Dimaleate
Subprotocol B (HER2 activating mutation)	Experimental	Patients with HER2 activating mutation receive afatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Afatinib Afatinib Dimaleate
Subprotocol C1 (MET amplification)	Experimental	Patients with MET amplification receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Crizotinib
Subprotocol C2 (MET exon 14 deletion/mutation)	Experimental	Patients with MET exon 14 deletion or other mutations that disrupt exon 14 receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Crizotinib
Subprotocol E (EGFR T790M or rare activating mutation)	Experimental	Patients with EGFR T790M or rare activating mutation receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Osimertinib
Subprotocol F (ALK translocation)	Experimental	Patients with ALK translocation receive crizotinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Crizotinib
Subprotocol G (ROS1 translocation or inversion)	Experimental	Patients with ROS1 translocation or inversion receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Crizotinib
Subprotocol H (BRAF V600E/R/K/D mutation)	Experimental	Patients with BRAF V600E/R/K/D mutation receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Dabrafenib Dabrafenib Mesylate Trametinib
Subprotocol I (PIK3CA mutation)	Experimental	Patients with PIK3CA mutation without RAS mutation or PTEN loss receive taselisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Taselisib
Subprotocol J (HER2 amplification >= 7 copy numbers)	Experimental	Patients with HER2 amplification >= 7 copy numbers receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.	Pertuzumab Trastuzumab Trastuzumab Emtansine
Subprotocol K1 (FGFR amplification)	Experimental	Patients with FGFR amplification receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Erdafitinib
Subprotocol K2 (FGFR mutation or fusion)	Experimental	Patients with FGFR mutation or fusion receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Erdafitinib
Subprotocol L (mTOR mutation)	Experimental	Patients with mTOR mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.	Sapanisertib
Subprotocol M (TSC1 or TSC2 mutation)	Experimental	Patients with TSC1 or TSC2 mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.	Sapanisertib
Subprotocol N (PTEN mutation or deletion and PTEN expression)	Experimental	Patients with PTEN mutation or deletion and PTEN expression receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	PI3K-beta Inhibitor GSK2636771
Subprotocol P (PTEN loss)	Experimental	Patients with PTEN loss receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	PI3K-beta Inhibitor GSK2636771
Subprotocol Q (HER2 amplification)	Experimental	Patients with HER2 amplification receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Trastuzumab Trastuzumab Emtansine
Subprotocol R (BRAF fusion or BRAF non-V600 mutation)	Experimental	Patients with BRAF fusion or BRAF non-V600 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Trametinib
Subprotocol S1 (NF1 mutation)	Experimental	Patients with NF1 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Trametinib
Subprotocol S2 (GNAQ or GNA11 mutation)	Experimental	Patients with GNAQ or GNA11 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Trametinib
Subprotocol T (SMO or PTCH1 mutation)	Experimental	Patients with SMO or PTCH1 mutation receive vismodegib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Vismodegib
Subprotocol U (NF2 inactivating mutation)	Experimental	Patients with NF2 inactivating mutation receive defactinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Defactinib Defactinib Hydrochloride
Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)	Experimental	Patients with cKIT exon 9, 11, 13, or 14 mutation receive sunitinib malate PO QD for 4 weeks. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Sunitinib Malate
Subprotocol W (FGFR pathway aberrations)	Experimental	Patients with FGFR1-3 mutation or translocation receive FGFR Inhibitor AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	FGFR Inhibitor AZD4547
Subprotocol X (DDR2 S768R, I638F, or L239R mutation)	Experimental	Patients with DDR2 S768R, I638F, or L239R mutation receive dasatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Dasatinib
Subprotocol Y (Akt mutation)	Experimental	Patients with Akt mutation receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Capivasertib
Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61)	Experimental	Patients with NRAS mutation in codon 12, 13, or 61 receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Binimetinib
Subprotocol Z1B (CCND1, 2, or 3 amplification with Rb by IHC)	Experimental	Patients with CCND1, 2, or 3 amplification that have tumor Rb expression by IHC receive palbociclib PO QD for 21 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Palbociclib
Subprotocol Z1C (CDK4 or CDK6 amplification and Rb protein)	Experimental	Patients with CDK4 or CDK6 amplification and tumor Rb protein receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Palbociclib
Subprotocol Z1D (Loss of MLH1 or MSH2 by IHC)	Experimental	Patients with mismatch repair deficiency (loss of MLH1 or MSH2 by IHC) receive nivolumab IV over 30 minutes on days 1 and 15 for 4 cycles and then on day 1 every 28 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Nivolumab
Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)	Experimental	Patients with NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Larotrectinib Larotrectinib Sulfate
Subprotocol Z1F (PIK3CA mutation)	Experimental	Patients with PIK3CA mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Copanlisib Copanlisib Hydrochloride
Subprotocol Z1G (PTEN loss)	Experimental	Patients with PTEN loss receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Copanlisib Copanlisib Hydrochloride
Subprotocol Z1H (PTEN mutation)	Experimental	Patients with PTEN mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Copanlisib Copanlisib Hydrochloride
Subprotocol Z1I (BRCA1 or BRCA2 gene mutation)	Experimental	Patients with BRCA1 or BRCA2 gene mutation receive adavosertib PO QD for 5 days for 2 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Adavosertib
Subprotocol Z1K (AKT mutation)	Experimental	Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Ipatasertib
Subprotocol Z1L (BRAF fusion, aberration or non-V600 mutation)	Experimental	Patients with a BRAF non-V600 mutation or BRAF fusion, or another BRAF aberration receive ulixertinib (BVD-523FB) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Ulixertinib
Subprotocol Z1M (LAG-3 expression >= 1%)	Experimental	Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1.Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Nivolumab Relatlimab

Eligibility Criteria

        Inclusion Criteria:

          -  ELIGIBILITY CRITERIA FOR SCREENING BIOPSY (STEP 0)

          -  Patients of childbearing potential must have a negative serum pregnancy test within 2
             weeks prior to registration; patients that are pregnant or breast feeding are
             excluded; a patient of childbearing potential is anyone, regardless of sexual
             orientation or whether they have undergone tubal ligation, who meets the following
             criteria:

               -  Has not undergone a hysterectomy or bilateral oophorectomy; or

               -  Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
                  has had menses at any time in the preceding 24 consecutive months)

          -  Patients of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for
             the duration of study participation, and for 4 months after completion of study;
             should a patient become pregnant or suspect while she or her partner is participating
             in this study, she should inform her treating physician immediately

          -  Patients must have histologically documented solid tumors or histologically confirmed
             diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the
             following criteria:

               -  Patients must have progressed following at least one line of standard systemic
                  therapy and there must not be other approval/standard therapy available that has
                  been shown to prolong overall survival (i.e. in a randomized trial against
                  another standard treatment or by comparison to historical controls); patients who
                  cannot receive other standard therapy that has been shown to prolong overall
                  survival due to medical issues will be eligible, if other eligibility criteria
                  are met; if the patient is currently receiving therapy, the clinician must have
                  assessed that the current therapy is no longer benefitting the patient prior to
                  enrolling on MATCH, regardless of whether it is considered standard OR

               -  Patients for whose disease no standard treatment exists that has been shown to
                  prolong overall survival

               -  NOTE: No other prior malignancy is allowed except for the following:

               -  Adequately treated basal cell or squamous cell skin cancer

               -  In situ cervical cancer

               -  Adequately treated stage I or II cancer from which the patient is currently in
                  complete remission

               -  Any other cancer from which the patient has been disease-free for 5 years

          -  Patients must have measurable disease

          -  Patients must meet the criteria below

               -  Tumor tissue for the confirmation of "rare variant" by the MATCH assay is to be
                  submitted, preferably from the same time of collection as that used to determine
                  patient candidacy for treatment arm assignment

                    -  Registration to Step 0 must occur after stopping prior systemic anti-cancer
                       therapy. There is no specific duration for which patients must be off
                       treatment prior to registration to Step 0, as long as all eligibility
                       criteria are met

                    -  Patients may have received other non-targeted, immunotherapy or targeted
                       treatment between the prior genetic testing at the outside lab and
                       registration to Step 0. The decision to stop such treatment in favor of
                       participation in MATCH, if no further clinical benefit is expected, is per
                       the treating physician's discretion. Documentation of a lack of response to
                       the prior treatment is not required in these cases

                    -  Patients with an applicable "rare variant" must be able to meet the
                       eligibility criteria for the appropriate subprotocols within 4 weeks
                       following notification of treatment assignment

                    -  Patient meets one of the following criteria:

                         -  Patient is a candidate for Z1M based on local CLIA assessment of MMRd
                            by immunohistochemistry (IHC) or MSI status by polymerase chain
                            reaction (PCR), adequate tumor tissue is available for submission for
                            mandatory central screening IHC and the patient will be able to meet
                            the eligibility criteria for Z1M within 4 weeks following notification
                            of treatment assignment OR

                         -  The sites has received results from one of the designated outside
                            laboratories indicating a "rare variant" that is an actionable Mutation
                            of Interest (aMOI) for specific select subprotocols

               -  NOTE: The outside laboratory specifically notified the site that patient may be a
                  potential candidate for MATCH due to a detected "rare variant." The outside lab
                  reports are NOT sufficient for this purpose. The content and format of these
                  specific referrals will vary depending on the designated outside lab in question,
                  as they are each responsible for their own outreach efforts. It is strongly
                  recommended that the designated outside laboratory be contacted to confirm the
                  format and receipt of this notification prior to registering any patients to Step
                  0. There is no particular window of time after notification of potential
                  eligibility from an outside lab in which the patient must be registered to Step
                  0, but treatment slots will be assigned on a first come, first serve basis to
                  those who do register to Step 0, and are not held for those notified of potential
                  eligibility who do not register to Step 0.

               -  NOTE: Treatment assignment (and the start of the associated deadline for Step 1
                  registration) may occur shortly after Step 0 registration. Note that certain
                  "rare variant" arms require submission of archival tissue for central IHC testing
                  to determine treatment assignment. For those arms, adequate tissue for the
                  central IHC is required to be available for submission

               -  NOTE: Other potential aMOIs that would be eligibility criteria for "NON RARE"
                  arms, as determined by the designated laboratories, are not applicable for this
                  process in MATCH

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
             and a life expectancy of at least 3 months

          -  Patients must be able to swallow tablets or capsules; a patient with any
             gastrointestinal disease that would impair ability to swallow, retain, or absorb drug
             is not eligible

          -  Patients who are human immunodeficiency virus (HIV)-positive are eligible if:

               -  CD4+ cell count greater or equal to 250 cells/mm^3

               -  If patient is on antiretroviral therapy, there must be minimal interactions or
                  overlapping toxicity of the antiretroviral therapy with the experimental cancer
                  treatment; for experimental cancer therapeutics with CYP3A/4 interactions,
                  protease inhibitor therapy is disallowed; suggested regimens to replace protease
                  inhibitor therapy include dolutegravir given with tenofovir/emtricitabine;
                  raltegravir given with tenofovir and emtricitabine; once daily combinations that
                  use pharmacologic boosters may not be used

               -  No history of non-malignancy acquired immune deficiency syndrome (AIDS)-defining
                  conditions other than historical low CD4+ cell counts

               -  Probable long-term survival with HIV if cancer were not present

          -  Any prior therapy, radiotherapy (except palliative radiation therapy of 30 gray [Gy]
             or less), or major surgery must have been completed >= 4 weeks prior to start of
             treatment; all adverse events due to prior therapy have resolved to a grade 1 or
             better (except alopecia and lymphopenia) by start of treatment; palliative radiation
             therapy must have been completed at least 2 weeks prior to start of treatment; the
             radiotherapy must not be to a lesion that is included as measurable disease

               -  NOTE: Prostate cancer patients may continue their luteinizing hormone-releasing
                  hormone (LHRH) agonist

               -  NOTE: For patients entering the study via the original screening process,
                  patients may receive non-protocol treatment after biopsy (if clinically
                  indicated) until they receive notification of results; however, lack of response
                  must be documented prior to registration to Step 1; new non-protocol treatment
                  will NOT be permitted as intervening therapy after registration to Step 0; the
                  only intervening treatment permitted is prior therapy that the patient already
                  received prior to Step 0 registration; the decision to stop the intervening
                  non-protocol treatment will be left up to the treating physician if patient has
                  an aMOI; however, patients will need to be off such therapy for at least 4 weeks
                  before receiving any MATCH protocol treatment

               -  NOTE: For patients entering the study via a designated outside laboratory, no
                  intervening systemic non-protocol treatment is permitted after Step 0
                  registration; all other eligibility requirements still apply to these patients,
                  including the washouts for prior therapy noted above in this section, the time
                  restrictions outlined, and the eligibility criteria for the intended subprotocol

          -  Patients with brain metastases or primary brain tumors must have completed treatment,
             surgery or radiation therapy >= 4 weeks prior to start of treatment

          -  Patients must have discontinued steroids >= 1 week prior to registration to Step 0 and
             remain off steroids thereafter, except as permitted; patients with glioblastoma (GBM)
             must have been on stable dose of steroids, or be off steroids, for one week prior to
             registration to treatment (Step 1, 3, 5, 7)

               -  NOTE: The following steroids are permitted (low dose steroid use is defined as
                  prednisone 10 mg daily or less, or bioequivalent dose of other corticosteroid):

                    -  Temporary steroid use: e.g. for computed tomography (CT) imaging in setting
                       of contrast allergy

                    -  Low dose steroid use for appetite

                    -  Chronic inhaled steroid use

                    -  Steroid injections for joint disease

                    -  Stable dose of replacement steroid for adrenal insufficiency or low doses
                       for non-malignant disease

                    -  Topical steroid

                    -  Steroids required to manage toxicity related to study treatment, as
                       described in the subprotocols

                    -  Steroids required as pre- or post-chemotherapy medication for acceptable
                       intervening chemotherapy

                         -  NOTE: Steroids must be completed alongside last dose of chemotherapy

          -  Leukocytes >= 3,000/mcL (within 2 weeks prior to screening step registration and
             within 4 weeks prior to treatment step registration)

          -  Absolute neutrophil count >= 1,500/mcL (within 2 weeks prior to screening step
             registration and within 4 weeks prior to treatment step registration)

          -  Platelets >= 100,000/mcL (within 2 weeks prior to screening step registration and
             within 4 weeks prior to treatment step registration)

          -  NOTE: Patients with documented bone marrow involvement by lymphoma are not required to
             meet the above hematologic parameters, but must have a platelet count of at least
             75,000/mcL and neutrophil count of at least 1,000/mcL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless documented
             Gilbert's syndrome, for which bilirubin =< 3 x institutional ULN is permitted) (within
             2 weeks prior to screening step registration and within 4 weeks prior to treatment
             step registration)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional ULN (up to 5 times ULN in presence of liver metastases) (within
             2 weeks prior to screening step registration and within 4 weeks prior to treatment
             step registration)

          -  Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above
             institutional normal

               -  As defined by the Cockcroft-Gault equation (within 2 weeks prior to screening
                  step registration and within 4 weeks prior to treatment step registration)

          -  Patients must have an electrocardiogram (ECG) within 8 weeks prior to registration to
             screening step and must meet the following cardiac criteria:

               -  Resting corrected QT interval (QTc) =< 480 msec

                    -  NOTE: If the first recorded QTc exceeds 480 msec, two additional,
                       consecutive ECGs are required and must result in a mean resting QTc =< 480
                       msec; it is recommended that there are 10-minute (+/- 5 minutes) breaks
                       between the ECGs

               -  The following only need to be assessed if the mean QTc > 480 msec

                    -  Check potassium and magnesium serum levels

                    -  Correct any identified hypokalemia and/or hypomagnesemia and may repeat ECG
                       to confirm exclusion of patient due to QTc

                    -  For patients with heart rate (HR) 60-100 beats per minute (bpm), no manual
                       read of QTc is required

                    -  For patients with baseline HR < 60 or > 100 bpm, manual read of QT by
                       trained personnel is required, with Fridericia correction applied to
                       determine QTc

                    -  Patient must not have hypokalemia (value < institutional lower limit of
                       normal)

               -  No factors that increase the risk of QTc prolongation or risk of arrhythmic
                  events such as heart failure, congenital long QT syndrome, family history of long
                  QT syndrome or unexplained sudden death under 40 years of age or any concomitant
                  medication known to prolong the QT interval

                    -  NOTE: Patient must be taken off prohibited medication prior to registration
                       to the screening step (Step 0, 2, 4, 6) and remain off these medications
                       thereafter, unless permitted on a subprotocol for the management of
                       treatment related toxicity; patient must be off the drug for at least 5
                       half-lives prior to registration to the treatment step (Step 1, 3, 5, 7);
                       the medication half-life can be found in the package insert for Food and
                       Drug Administration (FDA) approved drugs

          -  ELIGIBILITY CRITERIA FOR FIRST TREATMENT (STEP 1)

          -  NOTE: For patients entering step 0 with assay results from outside laboratories, no
             systemic treatment is allowed after step 0 registration

          -  As MATCH is designed to add additional subprotocols, implement limited expansions of
             accrual for certain subprotocols, and/or amend existing arm-specific eligibility
             criteria, some patients entering under the original screening method may be eligible
             to have their results rerun in MATCHbox, even if they did not match to a treatment
             initially or did not receive a treatment assignment due to a lack of available
             assignment slots; patients whose sequence results will be rerun through MATCHbox must
             also meet the following criteria:

               -  Samples must have been collected within 5 months of the activation of the
                  addendum, as there is an additional month needed to get the patients on trial

               -  Patient has not had treatment within the 5 months that resulted in a PR or better
                  after the performance of the screening assessment

               -  Patient must meet eligibility criteria, including performance status 1 or better
                  and life expectancy of at least 3 months

               -  Patients must meet the eligibility requirements with the following exceptions:

                    -  Patients may have received other non-targeted, immunotherapy or targeted
                       treatment, which could be stopped in favor of returning to MATCH, if no
                       response to the interim treatment has occurred and no further benefit is
                       expected from this interim treatment, per the treating physician's
                       discretion; documentation of a lack of response to the interim treatment is
                       not required in these cases; however, the following restrictions apply:

                         -  Enrollment onto another investigational therapeutic study is not
                            permitted

                         -  Patient cannot be responding to int

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Objective response rate
Time Frame:	Up to 3 years
Safety Issue:
Description:	Defined as the percentage of patients whose tumors have a complete or partial response to treatment. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria for solid tumors, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided confidence intervals will be calculated.

Secondary Outcome Measures

Measure:	Overall survival
Time Frame:	From registration onto that step until death, or censored at the date of last contact, assessed up to 3 years
Safety Issue:
Description:	Will be evaluated specifically for each drug (or step). Overall survival will be estimated using the Kaplan-Meier method.

Measure:	Progression free survival
Time Frame:	From entry onto that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months
Safety Issue:
Description:	Progression free survival will be estimated using the Kaplan-Meier method. For each treatment arm, 90% two-sided confidence intervals will be calculated.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	National Cancer Institute (NCI)

Last Updated

August 27, 2021

Clinical Trials /

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)