EAY131: Molecular Analysis for Therapy Choice (NCI-MATCH)

Why are we doing this research?

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.


Open treatment armsSee a list and description of available clinical trials for eligible patients with advanced solid tumors, lymphomas or myeloma.


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 or lymphomas.

DETAILED DESCRIPTION:

PRIMARY OBJECTIVES:

  • To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas.

SECONDARY OBJECTIVES:

  • 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.
  • 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) and protein-based assessment platforms.

Study Type: Interventional

Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Who can participate?

AGES ELIGIBLE FOR STUDY: 18 Years and older

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 that has progressed following at least one line of standard systemic therapy and/or for whose disease no standard treatment exists that has been shown to prolong 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, or any other cancer from which the patient has been disease-free for 5 years
  • Patients must have measurable disease
  • 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; biopsy must not be considered to be more than minimal risk to the patient
  • 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; stopping the anticoagulation for biopsy should be per site standard operating procedure (SOP)
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • 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
  • 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); (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:
  • Cluster of differentiation (CD)4+ 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 cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) 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 Gy or less), or major surgery must have been completed >= 4 weeks prior to treatment on Molecular Analysis for Therapy Choice (NCI-MATCH) and patient must be recovered from adverse events due to prior therapy (except alopecia and lymphopenia); palliative radiation therapy must have been completed at least 2 weeks prior to enrollment on a NCI-MATCH treatment subprotocol and patient must have recovered from any adverse events of this therapy
  • Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 4 weeks prior to registration to Step 0
  • Patients must have discontinued steroids >= 1 week prior to registration to Step 0; patients with glioblastoma (GBM) must have been on stable dose of steroids, or be off steroids, for one week prior to registration to Step 0
  • 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 =< 2 x normal institutional limits OR 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 have NONE of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) > 480 msec obtained from 3 consecutive ECGs; it is recommended that there are 10-minute (+/- 5 minutes) breaks between the ECGs
  • 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 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
  • No factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, 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
  • ELIGIBILITY CRITERIA FOR TREATMENT STEPS 1, 3, 5, and 7:
  • Eligibility requirements for registration are outlined in the agent-specific subprotocol
  • ELIGIBILITY CRITERIA FOR SCREENING STEPS 2, 4, 6, and 8:
  • Patient's disease has progressed on the prior Step treatment or patient could not tolerate assigned treatment
  • Patients must meet one of the following criteria:
  • No response and progression occurred < 6 months from start of the prior Step treatment AND the latest NCI-MATCH assay results indicated > 1 targeted treatment AND (Screening Steps 4 and 6 only) a biopsy was performed at the prior Screening Step
  • NOTE: Patients meeting these criteria will NOT be biopsied at this time point; instead, their Step 0 results will be re-interrogated to determine if another treatment is available
  • OR (Screening Step 2) progression occurred after a (1) response OR (2) after >= 6 months from start of Step 1 treatment; patient must have tumor amenable to percutaneous biopsy and be willing and able to undergo a tumor biopsy for collection and submission of tissue for the central determination of the presence of one or more of the specific "actionable" mutations/amplifications of interest (aMOI); patient must have tumor amenable to image guided or direct vision biopsy and be willing and able to undergo a tumor biopsy for molecular profiling; biopsy must not be considered to be more than minimal risk to the patient
  • OR (Screening Step 4) progression occurred on Step 3 treatment and a biopsy was not performed at Step 2 screening (due to presence of additional aMOIs at that stage); patient must have tumor amenable to percutaneous biopsy and be willing and able to undergo a tumor biopsy for collection and submission of tissue for the central determination of the presence of one or more of the specific "actionable" mutations/amplifications of interest; biopsy must not be considered to be more than minimal risk to the patient
  • Patients must meet eligibility criteria for biopsy as defined above
  • NOTE: A patient may have a maximum of 2 screening biopsies (not including re-biopsy due to assay failure), and 2 NCI-MATCH treatments per biopsy (if > 1 aMOI)
  • REGISTRATION TO RESEARCH BIOPSY (Step 8)
  • Patient has completed their most recent NCI-MATCH study treatment, will not undergo additional screening biopsies, and will receive no additional treatment on NCI-MATCH
  • NOTE: If a 2nd Screening Biopsy was performed and showed no study-actionable abnormalities, no additional end of treatment biopsy is requested
  • Patient's disease responded to the most recent NCI-MATCH study treatment and then progressed OR the disease progression is > 6 months since the last screening biopsy
Patient must have tumor amenable to percutaneous biopsy and be willing and able to undergo a tumor biopsy for collection and submission of tissue for research

Ages

  • From 18 to 99 years old

Conditions

  • Adult - Lymphoma Non Hodgkin Relapse
  • Adult - Lymphoma Hodgkin Relapse
  • Adult - Brain Spinal Tumors Medulloblastoma Relapse
  • Adult - Brain Spinal Tumor Low Grade Glioma Relapse
  • Adult - Brain Spinal Tumor DIPG Relapse
  • Adult - Brain and Spinal Tumor Ependymoma Relapse
  • Adult - Brain Spinal Neurofibromatosis Sarcoma MPNST Relapse
  • Adult - Brain Spinal Neurofibromatosis OPG
  • Adult - Brain Spinal Other All Other
  • Adult - Brain Spinal Other ATRT
  • Adult - Brain Spinal Other Choroid Plexus Tumor
  • Adult - Brain Spinal Other Craniopharyngioma
  • Adult - Brain Spinal Other Germ Cell Tumor
  • Adult - Sarcoma Ewing Relapse
  • Adult - Sarcoma Osteosarcoma Relapse
  • Adult - Sarcoma Rhabdomyosarcoma Relapse
  • Adult - Neuroblastoma Relapse - Refractory
  • Adult - Liver Relapse - Refractory
  • Adult - Kidney Relapse - Refractory
  • Adult - Solid Tumors - All Other
  • Adult - Solid Tumor Retinoblastoma Relapse - Refractory
  • Adult - Solid Tumor Neurofibromatosis Sarcoma MPNST Relapse - Refractory
  • Adult - Solid Tumor Neurofibromatosis OPG Low Grade Glioma
  • Adult - Solid Tumor Melanoma Relapse - Refractory
  • Adult - Solid Tumor Germ Cell Tumor Relapse - Refractory

Contact

For more information contact:

Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncolog
3333 Burnet Ave., Cincinnati OH 45229-3039

Phone: 513-636-2799

cancer@cchmc.org