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

 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 37 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.
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

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

 -  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; 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 patients entering step 0 with
 assay results from outside laboratories, no systemic treatment is allowed after step 0
 registration; the decision to stop the intervening nonprotocol treatment will be left
 up to the treating physician if patient has an aMOI; waiting periods as described will
 apply

 -  As MATCH is designed to add additional subprotocols, implement limited expansions of
 accrual for certain subprotocols, and/or amend existing arm-specific eligibility
 criteria, some patients entering under the original screening method may be eligible
 to have their results rerun in MATCHbox, even if they did not match to a treatment
 initially or did not receive a treatment assignment due to a lack of available
 assignment slots; patients whose sequence results will be rerun through MATCHbox must
 also meet the following criteria:

 -  Samples must have been collected within 5 months of the activation of the
 addendum, as there is an additional month needed to get the patients on trial

 -  Patient has not had treatment within the 5 months that resulted in a PR or better
 after the performance of the screening assessment

 -  Patient must meet eligibility criteria, including performance status 1 or better
 and life expectancy of at least 3 months

 -  Patients must meet the eligibility requirements with the following exceptions:

 -  Patients may have received other non-targeted, immunotherapy or targeted
 treatment, which could be stopped in favor of returning to MATCH, if no
 response to the interim treatment has occurred and no further benefit is
 expected from this interim treatment, per the treating physician's
 discretion; documentation o