Clinical Trials /

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

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:
  • Lymphoma
  • Malignant Solid Tumor
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

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 Carcinoma
  • Refractory Lymphoma
  • Refractory Malignant Solid Neoplasm
  • Refractory Plasma Cell Myeloma
  • Skin Carcinoma
  • Thyroid Gland Carcinoma
  • Uterine Corpus Cancer

Interventions

DrugSynonymsArms
AdavosertibAZD-1775, AZD1775, MK-1775, MK1775Subprotocol Z1I (BRCA1 or BRCA2 gene mutation)
AfatinibBIBW 2992Subprotocol A (EGFR activating mutation)
BinimetinibARRY-162, ARRY-438162, MEK162Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61)
CapivasertibAZD5363Subprotocol Y (Akt mutation)
CopanlisibBAY 80-6946, PI3K Inhibitor BAY 80-6946Subprotocol Z1H (PTEN mutation)
CrizotinibMET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, XalkoriSubprotocol F (ALK translocation)
DabrafenibBRAF Inhibitor GSK2118436, GSK-2118436A, GSK2118436Subprotocol H (BRAF V600E/R/K/D mutation)
DasatinibBMS-354825, SprycelSubprotocol X (DDR2 S768R, I638F, or L239R mutation)
DefactinibSubprotocol U (NF2 inactivating mutation)
ErdafitinibJNJ-42756493Subprotocol K1 (FGFR amplification)
FGFR Inhibitor AZD4547AZD4547Subprotocol W (FGFR pathway aberrations)
LarotrectinibARRY 470, LOXO 101, LOXO-101Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoSubprotocol Z1D (Loss of MLH1 or MSH2 by IHC)
OsimertinibAZD-9291, AZD9291, Mereletinib, TagrissoSubprotocol E (EGFR T790M or rare activating mutation)
PalbociclibIbrance, PD-0332991, PD-332991Subprotocol Z1B (CCND1, 2, or 3 amplification with Rb by IHC)
Pertuzumab2C4, 2C4 Antibody, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, rhuMAb2C4, RO4368451Subprotocol J (HER2 amplification >= 7 copy numbers)
PI3K-beta Inhibitor GSK2636771GSK2636771Subprotocol N (PTEN mutation or deletion and PTEN expression)
SapanisertibINK-128, INK128, MLN-0128, MLN0128, TAK-228Subprotocol L (mTOR mutation)
Sunitinib MalateSU011248, SU11248, sunitinib, SutentSubprotocol V (cKIT exon 9, 11, 13, or 14 mutation)
TaselisibGDC-0032, RO5537381Subprotocol I (PIK3CA mutation)
TrametinibGSK1120212, JTP-74057, MEK Inhibitor GSK1120212, MekinistSubprotocol H (BRAF V600E/R/K/D mutation)
Trastuzumab EmtansineAdo Trastuzumab Emtansine, ADO-TRASTUZUMAB EMTANSINE, Kadcyla, PRO132365, RO5304020, T-DM1, Trastuzumab-DM1, Trastuzumab-MCC-DM1, Trastuzumab-MCC-DM1 Antibody-Drug Conjugate, Trastuzumab-MCC-DM1 ImmunoconjugateSubprotocol Q (HER2 amplification)
VismodegibErivedge, GDC-0449, Hedgehog Antagonist GDC-0449Subprotocol T (SMO or PTCH1 mutation)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      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 35 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

NameTypeDescriptionInterventions
Subprotocol A (EGFR activating mutation)ExperimentalPatients with EGFR activating mutation receive afatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Afatinib
Subprotocol B (HER2 activating mutation)ExperimentalPatients with HER2 activating mutation receive afatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Afatinib
Subprotocol C1 (MET amplification)ExperimentalPatients with MET amplification receive crizotinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Crizotinib
Subprotocol C2 (MET exon 14 deletion)ExperimentalPatients with MET exon 14 deletion receive crizotinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Crizotinib
Subprotocol E (EGFR T790M or rare activating mutation)ExperimentalPatients with EGFR T790M or rare activating mutation receive osimertinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Osimertinib
Subprotocol F (ALK translocation)ExperimentalPatients with ALK translocation receive crizotinib PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Crizotinib
Subprotocol G (ROS1 translocation or inversion)ExperimentalPatients with ROS1 translocation or inversion receive crizotinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Crizotinib
Subprotocol H (BRAF V600E/R/K/D mutation)ExperimentalPatients with BRAF V600E/R/K/D mutation receive dabrafenib PO BID and trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Dabrafenib
  • Trametinib
Subprotocol I (PIK3CA mutation)ExperimentalPatients with PIK3CA mutation without RAS mutation or PTEN loss receive taselisib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Taselisib
Subprotocol J (HER2 amplification >= 7 copy numbers)ExperimentalPatients with HER2 amplification >= 7 copy numbers receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Pertuzumab
  • Trastuzumab Emtansine
Subprotocol K1 (FGFR amplification)ExperimentalPatients with FGFR amplification receive erdafitinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Erdafitinib
Subprotocol K2 (FGFR mutation or fusion)ExperimentalPatients with FGFR mutation or fusion receive erdafitinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Erdafitinib
Subprotocol L (mTOR mutation)ExperimentalPatients with mTOR mutation receive sapanisertib PO daily on days 1-28. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Sapanisertib
Subprotocol M (TSC1 or TSC2 mutation)ExperimentalPatients with TSC1 or TSC2 mutation receive sapanisertib PO daily on days 1-28. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Sapanisertib
Subprotocol N (PTEN mutation or deletion and PTEN expression)ExperimentalPatients with PTEN mutation or deletion and PTEN expression receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • PI3K-beta Inhibitor GSK2636771
Subprotocol P (PTEN loss)ExperimentalPatients with PTEN loss receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • PI3K-beta Inhibitor GSK2636771
Subprotocol Q (HER2 amplification)ExperimentalPatients with HER2 amplification receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Trastuzumab Emtansine
Subprotocol R (BRAF fusion or BRAF non-V600 mutation)ExperimentalPatients with BRAF fusion or BRAF non-V600 mutation receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Trametinib
Subprotocol S1 (NF1 mutation)ExperimentalPatients with NF1 mutation receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Trametinib
Subprotocol S2 (GNAQ or GNA11 mutation)ExperimentalPatients with GNAQ or GNA11 mutation receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Trametinib
Subprotocol T (SMO or PTCH1 mutation)ExperimentalPatients with SMO or PTCH1 mutation receive vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Vismodegib
Subprotocol U (NF2 inactivating mutation)ExperimentalPatients with NF2 inactivating mutation receive defactinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Defactinib
Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)ExperimentalPatients with cKIT exon 9, 11, 13, or 14 mutation receive sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
  • Sunitinib Malate
Subprotocol W (FGFR pathway aberrations)ExperimentalPatients with FGFR1-3 mutation or translocation receive FGFR Inhibitor AZD4547 PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • FGFR Inhibitor AZD4547
Subprotocol X (DDR2 S768R, I638F, or L239R mutation)ExperimentalPatients with DDR2 S768R, I638F, or L239R mutation receive dasatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Dasatinib
Subprotocol Y (Akt mutation)ExperimentalPatients with Akt mutation receive Akt inhibitor AZD5363 PO BID on days 1-4, 8-11, 15-18, and 22-25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Capivasertib
Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61)ExperimentalPatients with NRAS mutation in codon 12, 13, or 61 receive binimetinib PO BID on days 1-28. Courses 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)ExperimentalPatients with CCND1, 2, or 3 amplification that have tumor Rb expression by IHC receive palbociclib PO QD for 21 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Palbociclib
Subprotocol Z1C (CDK4 or CDK6 amplification and Rb protein)ExperimentalPatients with CDK4 or CDK6 amplification and tumor Rb protein receive palbociclib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Palbociclib
Subprotocol Z1D (Loss of MLH1 or MSH2 by IHC)ExperimentalPatients with mismatch repair deficiency (loss of MLH1 or MSH2 by IHC) receive nivolumab IV over 30 minutes on days 1 and 15 for 4 courses and then on day 1 every 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Nivolumab
Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)ExperimentalPatients with NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Larotrectinib
Subprotocol Z1F (PIK3CA mutation)ExperimentalPatients with PIK3CA mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Copanlisib
Subprotocol Z1G (PTEN loss)ExperimentalPatients with PTEN loss receive copanlisib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Copanlisib
Subprotocol Z1H (PTEN mutation)ExperimentalPatients with PTEN mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Copanlisib
Subprotocol Z1I (BRCA1 or BRCA2 gene mutation)ExperimentalPatients with BRCA1 or BRCA2 gene mutation receive adavosertib PO QD for 5 days for 2 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Adavosertib

Eligibility Criteria

        Inclusion Criteria:

          -  ELIGIBILITY CRITERIA FOR SCREENING BIOPSY (STEP 0)

          -  Women 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 female of childbearing potential is any woman, 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)

          -  Women 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 woman 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 and have 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.

               -  The following requirements apply:

                    -  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

                         -  NOTE: The content and format of these specific notifications for the
                            Outside Assay process 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

                    -  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

                         -  NOTE: The receipt of this notification (and the start of the associated
                            deadline for Step 1 registration) may occur shortly after Step 0
                            registration, since these patients will not be submitting tissue for
                            screening purposes; however, for certain "rare variant" arms,
                            submission of archival tissue for central immunohistochemistry (IHC)
                            testing may be required

                    -  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

                    -  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

                    -  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

                         -  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

                         -  NOTE: 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 evaluated by the designated outside laboratory

          -  Patient must not require the use of full dose coumarin-derivative anticoagulants such
             as warfarin; low molecular weight heparin is permitted for prophylactic or therapeutic
             use; factor X inhibitors are permitted

               -  NOTE: Warfarin may not be started while enrolled in the EAY131 study

               -  Stopping the anticoagulation for biopsy should be per site standard operating
                  procedure (SOP)

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
             and a life expectancy of at least 3 months

          -  Patients must not currently be receiving any other investigational agents

          -  Patients must not have any uncontrolled intercurrent illness including, but not
             limited to:

               -  Symptomatic congestive heart failure (New York Heart Association [NYHA]
                  classification of III/IV)

               -  Unstable angina pectoris or coronary angioplasty, or stenting within 6 months
                  prior to registration to Step 0, 2, 4, 6

               -  Cardiac arrhythmia (ongoing cardiac dysrhythmias of National Cancer Institute
                  [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]4 grade
                  >= 2)

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

               -  Intra-cardiac defibrillators

               -  Known cardiac metastases

               -  Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram
                  (ECHO) (as clinically indicated); (subjects with grade 1 abnormalities [i.e.,
                  mild regurgitation/stenosis] can be entered on study); subjects with moderate
                  valvular thickening should not be entered on study

               -  NOTE: To receive an agent, patient must not have any uncontrolled intercurrent
                  illness such as ongoing or active infection; patients with infections unlikely to
                  be resolved within 2 weeks following screening should not be considered for the
                  trial

          -  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 (see below); 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)

          -  If patients have been biopsied or submitted archived tumor tissue obtained within the
             last 6 months for assessment with the MATCH assays, patients may receive non-protocol
             treatment after biopsy/tissue submission (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; for pat
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate, defined as the percentage of patients whose tumors have a complete or partial response to treatment
Time Frame:Up to 3 years
Safety Issue:
Description: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, evaluated specifically for each drug (or step)
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: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.
Measure:Time to progression
Time Frame:From entry to that step until determination of disease progression or death due to disease, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years
Safety Issue:
Description:Time to progression will be estimated using the Kaplan-Meier method.

Details

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

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