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Title Molecular Analysis for Therapy Choice (MATCH)

IRB EAY131

CC 15-890

Hospital Main Campus, Main Campus

Disease All Cancer Types

Description

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

• 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.
• To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, RNA and protein-based assessment platforms.

Inclusion Criteria

NOTE: THIS CHECKLIST IS FOR ELIGIBILITY FOR THE MASTER SCREENING PROTOCOL ONLY; EACH ARM WILL HAVE ADDITIONAL ELIGIBILITY CRITERIA THAT WILL BE OUTLINED IN SECTION 2.1 OF THE AGENT-SPECIFIC SUBPROTOCOL.

Registration to Screening Biopsy (Step 0)

1. Patients must be ≥ 18 years of age. Because no dosing or adverse event data are currently available on the use of study investigational agents in patients < 18 years of age, children are excluded from this study.
2. 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: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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).
3. 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.
4. 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.
5. Patients must have measurable disease as defined in Section 6.
6. 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. See Section 9.
7. 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 SOP.
8. Patients must have ECOG performance status ≤ 1, see Appendix V.
9. Patients must not currently be receiving any other investigational agents.
10. Patients must not have any uncontrolled intercurrent illness including, but not limited to:
    • Symptomatic congestive heart failure (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 NCI CTCAE v4 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 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.

11. 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.
12. Patients who are HIV-positive are eligible if:
    • CD4+ cell count greater or equal to 250 cells/mm³
    • 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/emtracitabine; raltegravir given with tenofovir and emtracitabine. Once daily combinations that use pharmacologic boosters may not be used.
    • No history of non-malignancy AIDS-defining conditions other than historical low CD4+ cell counts
    • Probable long-term survival with HIV if cancer were not present.
13. 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 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 MATCH treatment arm and patient must have recovered from any adverse events of this therapy.
14. Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy ≥ 4 weeks prior to registration to Step 0.
15. 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.
16. Patients must have adequate organ and marrow function as defined below within 2 weeks prior to registration to Step 0 and all subsequent steps:
    • 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 1000/mcL.

    • Total bilirubin ≤1.5 X institutional ULN (unless documented Gilbert's Syndrome, for which bilirubin ≤ 3 x institutional ULN is permitted)
    • AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal (ULN) (up to 5 times ULN in presence of liver metastases)
    • Creatinine ≤ 2x normal institutional limits OR Creatinine clearance ≥ 45 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
17. 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 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 (For a list of these medications, visit https://www.crediblemeds.org/index.php/login/dlcheck)

Registration to First Treatment (Step 1)

1. Eligibility requirements for registration onto Step 1 are outlined in Section 2.1 of the agent-specific subprotocol.

Registration to Second Screening (Step 2)

1. Patient's disease has progressed on Step 1 treatment (per Section 6) or could not tolerate assigned treatment.
2. Patients must meet one of the following criteria:
   • No response and progression occurred < 6 months from start of Step 1 treatment AND the MATCH assay results (received during Step 0) indicated > 1 targeted treatment.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
   • 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) (defined in Appendix VII). 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. See Section 9.
3. Patients must meet eligibility criteria for biopsy as defined in Section 3.1.

Registration to Second Treatment (Step 3)

1. Eligibility requirements for registration onto Step 3 are outlined in Section 2.1 of the agent-specific subprotocol.

Registration to Third Screening (Step 4)

1. Patient's disease has progressed on Step 3 treatment or could not tolerate assigned treatment.
2. Patients must meet one of the following criteria:
   • No response and progression occurred < 6 months from start of Step 3 (second) treatment AND the latest MATCH assay results indicated >1 targeted treatments AND a biopsy was performed at Step 2 screening. NOTE: Patients meeting these criteria will NOT be biopsied at this time point. Instead, their results will be re-interrogated to determine if another treatment is available. OR
   • 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 (defined in Appendix VII). Biopsy must not be considered to be more than minimal risk to the patient. See Section 9.
3. Patients must meet eligibility criteria for biopsy as defined in Section 3.1. NOTE: A patient may have a maximum of 2 screening biopsies (not including re-biopsy due to assay failure) , and 2 MATCH treatments per biopsy (if > 1 aMOI)

Registration to Third Treatment (Step 5)

1. Eligibility requirements for registration onto Step 5 are outlined in Section 2.1 of the agent-specific subprotocol.

Registration to Fourth Screening (Step 6)

1. Patient's disease has progressed on Step 5 protocol treatment or could not tolerate assigned treatment.
2. No response and progression occurred < 6 months from start of Step 5 treatment AND the MATCH assay results of the 2nd biopsy indicated > 1 targeted treatments AND a biopsy was performed at Step 4 screening. NOTE: Patients meeting these criteria will NOT be biopsied at this time point. Instead, based on their 2nd biopsy, their results will be interrogated to determine if another treatment is available.
3. Patients must meet eligibility criteria for biopsy as defined in Section 3.1 of this screening protocol. NOTE: A patient may have a maximum of 2 screening biopsies (not including re-biopsy due to assay failure), and 2 MATCH treatments per biopsy (if > 1 aMOI)

Registration to Fourth Treatment (Step 7)

1. Eligibility requirements for registration onto Step 7 are outlined in Section 2.1 of the agent-specific subprotocol.

Registration to Research Biopsy (Step 8)

1. Patient has completed their most recent MATCH study treatment, will not undergo an additional screening biopsies, and will receive no additional treatment on MATCH. NOTE: If a 2nd Screening Biopsy was performed and showed no study-actionable abnormalities, no additional end of treatment biopsy is requested.
2. Patient's disease responded to the most recent MATCH study treatment and then progressed OR the disease progression is > 6 months since the last screening biopsy.
3. 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.

Exclusion Criteria