We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    02465060
Previous Study | Return to List | Next Study

NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma

This study is currently recruiting participants.
Verified November 2017 by National Cancer Institute (NCI)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02465060
First Posted: June 8, 2015
Last Update Posted: December 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This phase II 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.

Condition Intervention Phase
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 Drug: Afatinib Drug: Akt inhibitor AZD5363 Drug: Binimetinib Drug: Crizotinib Other: Cytology Specimen Collection Procedure Drug: Dabrafenib Drug: Dasatinib Drug: Defactinib Drug: FGFR Inhibitor AZD4547 Other: Laboratory Biomarker Analysis Drug: Larotrectinib Biological: Nivolumab Drug: Osimertinib Drug: Palbociclib Biological: Pertuzumab Drug: PI3K-beta Inhibitor GSK2636771 Drug: Sapanisertib Drug: Sunitinib Malate Drug: Taselisib Drug: Trametinib Biological: Trastuzumab Emtansine Drug: Vismodegib Drug: WEE1 Inhibitor AZD1775 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Molecular Analysis for Therapy Choice (MATCH)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ]
    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, 80% two-sided confidence intervals will be calculated.


Secondary Outcome Measures:
  • 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 ]
    Overall survival will be estimated using the Kaplan-Meier method.

  • 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 ]
    Progression free survival will be estimated using the Kaplan-Meier method. For each treatment arm, 80% two-sided confidence intervals will be calculated.

  • 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 ]
    Time to progression will be estimated using the Kaplan-Meier method.


Other Outcome Measures:
  • Biomarkers that provide clues for mechanisms of acquired resistance [ Time Frame: Up to 3 years ]
    Biomarkers measured at time of progression might provide clues for mechanisms of acquired resistance. Changes in biomarker levels from baseline (prior to receiving the treatment) to progression within patients will be assessed using paired tests appropriate for the type of biomarker measurement (e.g., paired t-tests for normally distributed biomarker values or McNemar tests for paired binary data). It will also be assessed whether patterns of changes in biomarkers are different depending on length of time to progression.

  • Potential predictive biomarkers beyond the genomic alteration [ Time Frame: Baseline ]
    Biomarkers measured prior to treatment could be predictive of response or non-response to the agent. Analyses conducted to identify predictive biomarkers will be primarily exploratory and will consist of simple comparisons of biomarkers levels, either using binomial-based tests (for binary biomarkers), t-tests (continuous biomarkers, possibly transformed), or non-parametric tests, as appropriate depending on the distribution of the biomarker values.


Estimated Enrollment: 6452
Actual Study Start Date: August 12, 2015
Estimated Study Completion Date: June 30, 2022
Estimated Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Subprotocol A (EGFR activating mutation)
Patients 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.
Drug: Afatinib
Given PO
Other Name: BIBW 2992
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol B (HER2 activating mutation)
Patients 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.
Drug: Afatinib
Given PO
Other Name: BIBW 2992
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol C1 (MET amplification)
Patients 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.
Drug: Crizotinib
Given PO
Other Names:
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
  • PF-2341066
  • Xalkori
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol C2 (MET exon 14 deletion)
Patients 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.
Drug: Crizotinib
Given PO
Other Names:
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
  • PF-2341066
  • Xalkori
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol E (EGFR T790M or rare activating mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Osimertinib
Given PO
Other Names:
  • AZD-9291
  • AZD9291
  • Mereletinib
  • Tagrisso
Experimental: Subprotocol F (ALK translocation)
Patients 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.
Drug: Crizotinib
Given PO
Other Names:
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
  • PF-2341066
  • Xalkori
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol G (ROS1 translocation or inversion)
Patients 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.
Drug: Crizotinib
Given PO
Other Names:
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
  • PF-2341066
  • Xalkori
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol H (BRAF V600E/R/K/D mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Drug: Dabrafenib
Given PO
Other Names:
  • BRAF Inhibitor GSK2118436
  • GSK-2118436A
  • GSK2118436
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Trametinib
Given PO
Other Names:
  • GSK1120212
  • JTP-74057
  • MEK Inhibitor GSK1120212
  • Mekinist
Experimental: Subprotocol I (PIK3CA mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Taselisib
Given PO
Other Name: GDC-0032
Experimental: Subprotocol J (HER2 amplification >= 7 copy numbers)
Patients with HER2 amplification >= 7 copy numbers receive pertuzumab IV over 30-60 minutes and trastuzumab emtansine IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Biological: Pertuzumab
Given IV
Other Names:
  • 2C4
  • 2C4 Antibody
  • MoAb 2C4
  • Monoclonal Antibody 2C4
  • Perjeta
  • rhuMAb2C4
  • RO4368451
Biological: Trastuzumab Emtansine
Given IV
Other Names:
  • 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
Experimental: Subprotocol L (mTOR mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Sapanisertib
Given PO
Other Names:
  • INK-128
  • INK128
  • MLN-0128
  • MLN0128
  • TAK-228
Experimental: Subprotocol M (TSC1 or TSC2 mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Sapanisertib
Given PO
Other Names:
  • INK-128
  • INK128
  • MLN-0128
  • MLN0128
  • TAK-228
Experimental: Subprotocol N (PTEN mutation or deletion and PTEN expression)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: PI3K-beta Inhibitor GSK2636771
Given PO
Other Name: GSK2636771
Experimental: Subprotocol P (PTEN loss)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: PI3K-beta Inhibitor GSK2636771
Given PO
Other Name: GSK2636771
Experimental: Subprotocol Q (HER2 amplification)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Biological: Trastuzumab Emtansine
Given IV
Other Names:
  • 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
Experimental: Subprotocol R (BRAF fusion or BRAF non-V600 mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Trametinib
Given PO
Other Names:
  • GSK1120212
  • JTP-74057
  • MEK Inhibitor GSK1120212
  • Mekinist
Experimental: Subprotocol S1 (NF1 mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Trametinib
Given PO
Other Names:
  • GSK1120212
  • JTP-74057
  • MEK Inhibitor GSK1120212
  • Mekinist
Experimental: Subprotocol S2 (GNAQ or GNA11 mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Trametinib
Given PO
Other Names:
  • GSK1120212
  • JTP-74057
  • MEK Inhibitor GSK1120212
  • Mekinist
Experimental: Subprotocol T (SMO or PTCH1 mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Vismodegib
Given PO
Other Names:
  • Erivedge
  • GDC-0449
  • Hedgehog Antagonist GDC-0449
Experimental: Subprotocol U (NF2 inactivating mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Drug: Defactinib
Given PO
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Sunitinib Malate
Given PO
Other Names:
  • SU011248
  • SU11248
  • sunitinib
  • Sutent
Experimental: Subprotocol W (FGFR pathway aberrations)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Drug: FGFR Inhibitor AZD4547
Given PO
Other Name: AZD4547
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol X (DDR2 S768R, I638F, or L239R mutation)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Drug: Dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol Y (Akt mutation)
Patients 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.
Drug: Akt inhibitor AZD5363
Given PO
Other Name: AZD5363
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61)
Patients 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.
Drug: Binimetinib
Given PO
Other Names:
  • ARRY-162
  • ARRY-438162
  • MEK162
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Experimental: Subprotocol Z1B (CCND1, 2, or 3 amplification with Rb by IHC)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Palbociclib
Given PO
Other Names:
  • Ibrance
  • PD-0332991
  • PD-332991
Experimental: Subprotocol Z1C (CDK4 or CDK6 amplification and Rb protein)
Patients 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Palbociclib
Given PO
Other Names:
  • Ibrance
  • PD-0332991
  • PD-332991
Experimental: Subprotocol Z1D (Loss of MLH1 or MSH2 by IHC)
Patients with mismatch repair deficiency (loss of MLH1 or MSH2 by IHC) receive nivolumab IV over 60 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.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Experimental: Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
Patients with NTRK1, NTRK2, or NTRK3 gene fusion receive trk inhibitor LOXO-101 PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Cytology Specimen Collection Procedure
Optional correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Larotrectinib
Given PO
Other Names:
  • ARRY 470
  • LOXO 101
  • LOXO-101
Experimental: Subprotocol Z1I (BRCA1 or BRCA2 gene mutation)
Patients with BRCA1 or BRCA2 gene mutation receive WEE1 inhibitor AZD1775 PO QD for 5 days for 2 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: WEE1 Inhibitor AZD1775
Given PO
Other Names:
  • AZD-1775
  • AZD1775
  • MK-1775
  • MK1775

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 30 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 one of the following criteria:

    • Patients must have tumor amenable to image guided or direct vision biopsy and be willing and able to undergo a tumor biopsy for molecular profiling; patients with multiple myeloma other than plasmacytomas are to have a bone marrow aspirate to obtain tumor cells; biopsy must not be considered to be more than minimal risk to the patient

      • NOTE: Registration to screening steps (Step 0, 2, 4, 6) must occur after stopping prior therapy; there is no specific duration for which patients must be off treatment prior to registration to the relevant screening step (and subsequently, the biopsy), as long as all other eligibility criteria are met OR
    • Patient will be undergoing a procedure due to medical necessity during which the tissue may be collected

      • NOTE: Registration to screening steps (Step 0, 2, 4, 6) must occur after stopping prior therapy; there is no specific duration for which patients must be off treatment prior to registration to the relevant screening step (and subsequently, the biopsy), as long as all other eligibility criteria are met OR
    • Formalin-fixed paraffin-embedded tumor tissue block(s) are available for submission following pre-registration (not applicable for bone marrow aspirate specimens); criteria for the submission of formalin-fixed paraffin-embedded (FFPE) tissue are:

      • Tissue must have been collected within 6 months prior to pre-registration to Step 0

        • Patient may receive treatment after tissue collection; however, lack of response must be documented prior to Step 1; the following restrictions apply:

          • Enrollment onto another investigational study is not permitted
          • Intervening therapy that constitutes a new, molecularly targeted therapy is not permitted; please note, immunotherapy is not considered molecularly targeted

            • Continuation of an agent/regimen for which disease progression has been observed prior to biopsy is permitted, including targeted therapy
          • A new immunotherapy regimen is permitted; but, lack of response must also be documented prior to registration to Step 0
      • Formalin-fixed paraffin-embedded tumor tissue block(s) must meet the minimum requirements OR
    • Results from one of the designated outside laboratories indicate a "rare variant" that is an actionable mutation of interest (aMOI) for specific designated rare variant subprotocols; the following requirements apply:

      • The outside laboratory notified the site that patient may be a potential candidate for MATCH due to a detected "rare variant"
      • Patients with an applicable "rare variant" must be able to meet the eligibility criteria for the appropriate subprotocols within 4 weeks following entry on the EAY131 Step 0 screening step
      • 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

        • NOTE: Other potential aMOIs that would be eligibility criteria for NON RARE arms, as determined by the above laboratories, are not applicable for direct treatment assignment on 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: 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 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 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
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • 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)
  • 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)
  • Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02465060


  Show 1192 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Keith Flaherty ECOG-ACRIN Cancer Research Group
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02465060     History of Changes
Other Study ID Numbers: NCI-2015-00054
NCI-2015-00054 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EAY131
EAY131 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EAY131 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
U24CA196172 ( U.S. NIH Grant/Contract )
First Submitted: June 3, 2015
First Posted: June 8, 2015
Last Update Posted: December 15, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Lymphoma
Carcinoma
Neoplasms
Melanoma
Multiple Myeloma
Neoplasms, Plasma Cell
Glioma
Thyroid Diseases
Breast Neoplasms
Lung Neoplasms
Endometrial Neoplasms
Colorectal Neoplasms
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Prostatic Neoplasms
Pancreatic Neoplasms
Esophageal Neoplasms
Stomach Neoplasms
Rectal Neoplasms
Urinary Bladder Neoplasms
Colonic Neoplasms
Uterine Neoplasms
Carcinoma, Hepatocellular
Carcinoma, Ductal
Thyroid Neoplasms
Skin Neoplasms
Carcinoma, Renal Cell
Kidney Neoplasms
Cholangiocarcinoma
Neoplasms by Histologic Type