Clinical Trials /

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

NCT02693535

Description:

The purpose of the study is to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target or to predict sensitivity to a drug. NOTE: Due to character limits, the arms section does NOT include all TAPUR Study relevant biomarkers. For additional information, contact TAPUR@asco.org, or if a patient, your nearest participating TAPUR site (see participating centers).

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Bile Duct Carcinoma
  • Bladder Carcinoma
  • Breast Carcinoma
  • Bronchogenic Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Esophageal Squamous Cell Carcinoma
  • Fallopian Tube Carcinoma
  • Gallbladder Carcinoma
  • Gastric Adenocarcinoma
  • Lung Carcinoma
  • Malignant Solid Tumor
  • Malignant Uterine Neoplasm
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer
  • Official Title: Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Clinical Trial IDs

  • ORG STUDY ID: Pro00014171
  • NCT ID: NCT02693535

Conditions

  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
CrizotinibXalkoriGroup 3 (ALK, ROS1, MET)
PalbociclibIbranceGroup 4 (CDKN2A, CDK4, CDK6)
SunitinibSutentGroup 5 (CSF1R,PDGFR,VEGFR)
TemsirolimusToriselGroup 6 (mTOR, TSC)
Trastuzumab and PertuzumabHerceptin and PerjetaGroup 8 (ERBB2)
Vemurafenib and CobimetinibZelboraf and CotellicGroup 9 (BRAF V600E/D/K/R)
RegorafenibStivargaGroup 13 (RET,VEGFR1/2/3,KIT,PDGFRβ,RAF-1,BRAF)
OlaparibLynparzaGroup 14 (BRCA1/2; ATM)
PembrolizumabKeytrudaGroup 15 (POLE, POLD1, high mutational load)
Nivolumab and IpilimumabOpdivo and YervoyGroup 16 (MSI-H, high mutational load and others)
AbemaciclibVerzenioGroup 17 (CDKN2A, CDK4, CDK6)
AfatinibGilotrifGroup 18 (NRG1)
TalazoparibTalzennaGroup 19 (BRCA1/2, PALB2)

Purpose

The purpose of the study is to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target or to predict sensitivity to a drug. NOTE: Due to character limits, the arms section does NOT include all TAPUR Study relevant biomarkers. For additional information, contact TAPUR@asco.org, or if a patient, your nearest participating TAPUR site (see participating centers).

Detailed Description

      The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a non-randomized
      clinical trial that aims to describe the safety and efficacy of commercially available,
      targeted anticancer drugs prescribed for treatment of patients with advanced cancer that has
      a potentially actionable genomic variant. TAPUR will study Food and Drug Administration
      (FDA)-approved targeted therapies that are contributed by collaborating pharmaceutical
      companies, catalogue the choice of molecular profiling test by clinical oncologists and
      develop hypotheses for additional clinical trials.
    

Trial Arms

NameTypeDescriptionInterventions
Group 3 (ALK, ROS1, MET)OtherParticipants receive crizotinib - dosage, frequency and duration per label; acceptable genomic matches include ALK fusion or mutation, ROS1 fusion, MET amplification or mutation, MET exon 14 alteration, RON amplification or mutation
  • Crizotinib
Group 4 (CDKN2A, CDK4, CDK6)OtherParticipants receive palbociclib - dosage, frequency and duration per label; acceptable genomic matches include CDKN2A loss or mutation, CDK4, CDK6 amplifications
  • Palbociclib
Group 5 (CSF1R,PDGFR,VEGFR)OtherParticipants receive sunitinib - dosage, frequency and duration per label; acceptable genomic matches include CSF1R, PDGFR, VEGFR1/2/3, KIT, FLT-3, RET, FGFR1/2/3, VHL amplifications or mutations
  • Sunitinib
Group 6 (mTOR, TSC)OtherParticipants receive temsirolimus - dosage, frequency and duration per label; acceptable genomic matches include mTOR, TSC1/2, AKT1 mutations
  • Temsirolimus
Group 8 (ERBB2)OtherParticipants receive trastuzumab and pertuzumab - dosage, frequency and duration per label; acceptable genomic matches include ERBB2 amplification, overexpression, and specific mutations
  • Trastuzumab and Pertuzumab
Group 9 (BRAF V600E/D/K/R)OtherParticipants receive vemurafenib and cobimetinib - dosage, frequency and duration per label; acceptable genomic matches include BRAF V600E/D/K/R mutations
  • Vemurafenib and Cobimetinib
Group 13 (RET,VEGFR1/2/3,KIT,PDGFRβ,RAF-1,BRAF)OtherParticipants receive regorafenib - dosage, frequency and duration per label; acceptable genomic matches include RET, VEGFR1/2/3, KIT, PDGFRβ, RAF-1, BRAF mutations or amplifications
  • Regorafenib
Group 14 (BRCA1/2; ATM)OtherParticipants receive olaparib - dosage, frequency and duration per label; acceptable genomic matches include germline or somatic BRCA1/2 inactivating mutations; ATM mutations or deletions
  • Olaparib
Group 15 (POLE, POLD1, high mutational load)OtherParticipants receive pembrolizumab - dosage, frequency and duration per label; acceptable genomic matches include specific POLE and POLD1 mutations, tumor mutational burden as defined in protocol
  • Pembrolizumab
Group 16 (MSI-H, high mutational load and others)OtherParticipants receive nivolumab and ipilimumab - dosage, frequency and duration per label; acceptable genomic matches include MSI high status, high tumor mutational burden, MLH1, MSH2/6, PMS2, EPCAM mutations, specific POLE or POLD1 mutations, BRCA1/2, ATM, MSH3, PMS1, MLH3, EXO1, RFC1/2/3/4/5, PCNA, RPA1/2/3/4, and SSBP1 loss of function mutations
  • Nivolumab and Ipilimumab
Group 17 (CDKN2A, CDK4, CDK6)OtherParticipants receive abemaciclib - dosage, frequency and duration per label; acceptable genomic matches include CDKN2A loss or mutation, CDK4, CDK6 amplifications
  • Abemaciclib
Group 18 (NRG1)OtherParticipants receive afatinib - dosage, frequency and duration per label; acceptable genomic matches include NRG1 fusions
  • Afatinib
Group 19 (BRCA1/2, PALB2)OtherParticipants receive Participants receive talazoparib - dosage, frequency and duration per label; acceptable genomic matches include germline or somatic BRCA1/2 and PALB2 mutations
  • Talazoparib

Eligibility Criteria

        Inclusion Criteria:

          -  12 years of age or older (*Restrictions apply. Not all therapies are available for
             patients <18)

          -  Histologically-proven locally advanced or metastatic solid tumor, multiple myeloma or
             B cell non-Hodgkin lymphoma who is no longer benefiting from standard anti-cancer
             treatment or for whom, in the opinion of the treating physician, no such treatment is
             available or indicated

          -  Performance status 0-2 (Per Eastern Cooperative Oncology Group (ECOG) criteria)

          -  Patients must have acceptable organ function as defined below. However, as noted
             above, drug-specific inclusion/exclusion criteria specified in the protocol appendix
             for each agent will take precedence for this and all inclusion criteria:

               1. Absolute neutrophil count ≥ 1.5 x 106/µl

               2. Hemoglobin > 9.0 g/dl

               3. Platelets > 75,000/µl

               4. Total bilirubin < 2.0 mg/ dl, except in patients with Gilbert's Syndrome

               5. Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)
                  and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) <
                  2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with
                  known hepatic metastases)

               6. Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50
                  mL/min/1.73 m2

          -  Patients must have measurable or evaluable disease (per RECIST v1.1 for solid tumor,
             Lugano criteria for non Hodgkin lymphoma or International Myeloma Working Group
             criteria for multiple myeloma), defined, as at least one lesion that can be accurately
             measured in at least one dimension (longest diameter to be recorded for non-nodal
             lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as
             ≥10 mm with spiral computed tomography (CT) scan, Magnetic Resonance Imaging (MRI), or
             a subcutaneous or superficial lesion that can be measured with calipers by clinical
             exam. For lymph nodes, the short axis must be ≥15 mm. Patients who have assessable
             disease by physical or radiographic examination but do not meet these definitions of
             measurable disease are eligible and will be considered to have evaluable disease.
             Patient's whose disease cannot be objectively measured by physical or radiographic
             examination (e.g., elevated serum tumor marker only) are NOT eligible

          -  Results must be available from a genomic test or immunohistochemistry (IHC) test for
             protein expression performed in a Clinical Laboratory Improvement Amendments
             (CLIA)-certified and College of American Pathologists (CAP)-accredited or New York
             State accredited (for labs offering services to residents of NY) laboratory that has
             registered the test with the National Institutes of Health (NIH) Genetic Test Registry
             or has established an integration with the TAPUR platform. The genomic or IHC test
             used to qualify a patient for participation in TAPUR may have been performed on any
             specimen of the patient's tumor obtained at any point during the patient's care at the
             discretion of the patient's treating physician. Genomic assays performed on cell-free
             DNA in plasma ("liquid biopsies") will also be acceptable if the genomic analysis is
             performed in a laboratory that meets the criteria described above.

          -  Ability to understand and the willingness to sign a written informed consent/assent
             document

          -  Have a tumor genomic profile for which single agent treatment with one of the FDA
             approved targeted anti-cancer drugs included in this study has potential clinical
             benefit based on the criteria described in protocol

          -  For orally administered drugs, the patient must be able to swallow and tolerate oral
             medication and must have no known malabsorption syndrome

          -  Because of the risks of drug treatment to the developing fetus, women of child-bearing
             potential and men must agree to use adequate contraception (hormonal or barrier method
             of birth control; abstinence) for the duration of study participation, and for four
             months following completion of study therapy. Should a woman become pregnant or
             suspect she is pregnant while participating in this study or if she is the partner of
             a male participant in this study and becomes pregnant while he is participating in
             this study, she should inform her or her partner's treating physician immediately as
             well as her obstetrician. Female study patients who become pregnant must immediately
             discontinue treatment with any study therapy. Male patients should avoid impregnating
             a female partner. Male study patients, even if surgically sterilized, (i.e.
             post-vasectomy) must agree to one of the following: practice effective barrier
             contraception during the entire study treatment period and through 4 months after the
             last dose of study drug, or completely abstain from sexual intercourse

        Note: TAPUR does not explicitly exclude any type of solid tumor, but the patient must have
        measurable and evaluable disease per RECIST v1.1

        Exclusion Criteria:

          -  Patients whose disease is not measurable or cannot be assessed by radiographic imaging
             or physical examination (e.g., elevated serum tumor marker only) are not eligible

          -  Patients with primary brain tumors or leptomeningeal metastases are excluded

          -  Patients with previously treated brain metastases are eligible, provided that the
             patient has not experienced a seizure or had a clinically significant change in
             neurological status within the 3 months prior to registration. All patients with
             previously treated brain metastases must be clinically stable for at least 1 month
             after completion of treatment and off steroid treatment for one month prior to study
             enrollment.

          -  Patients with known progressive brain metastases are eligible but additional
             eligibility criteria apply

        Note: there are additional exclusion criteria that may apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate defined as % of participants in a cohort with complete or partial response or with stable disease according to standard response criteria
Time Frame:Assessed at 16 weeks of treatment
Safety Issue:
Description:Each cohort includes participants with the same tumor type, genomic variant and study drug. For solid tumors, the Response Evaluation Criteria for Solid Tumors (RECIST) criteria will be used, for non-Hodgkin Lymphoma, the Lugano Criteria will be used, and for multiple myeloma, the International Uniform Response Criteria for Multiple Myeloma will be used.

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Duration of survival from registration on study until death from any cause, assessed throughout end of study, up to 3 years
Safety Issue:
Description:OS will be estimated using the Kaplan-Meier method

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:American Society of Clinical Oncology

Trial Keywords

  • cancer
  • off-label
  • precision medicine
  • targeted therapy

Last Updated

December 12, 2019