Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
Purpose
This phase II MATCH screening and multi-sub-trial studies how well treatment that is directed by genetic testing works in patients with solid tumors, lymphomas, or multiple myelomas that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and does not respond to treatment (refractory). Patients must 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.
Conditions
- Advanced Lymphoma
- Advanced Malignant Solid Neoplasm
- Bladder Carcinoma
- Breast Carcinoma
- Cervical Carcinoma
- Colon Carcinoma
- Colorectal Carcinoma
- Endometrial Carcinoma
- Esophageal Carcinoma
- Exocrine Pancreas Carcinoma
- Gastric Carcinoma
- Glioma
- Head and Neck Carcinoma
- Hematopoietic and Lymphoid Cell Neoplasm
- Kidney Carcinoma
- Liver Carcinoma
- Lung Carcinoma
- Lymphoma
- Malignant Uterine Corpus Neoplasm
- Malignant Uterine Neoplasm
- Melanoma
- Multiple Myeloma
- Ovarian Carcinoma
- 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 Malignant Uterine Corpus Neoplasm
- Recurrent Melanoma
- Recurrent Multiple Myeloma
- Recurrent Ovarian Carcinoma
- Recurrent Pancreatic Carcinoma
- Recurrent Prostate Carcinoma
- Recurrent Rectal Carcinoma
- Recurrent Skin Carcinoma
- Recurrent Thyroid Gland Carcinoma
- Refractory Lymphoma
- Refractory Malignant Solid Neoplasm
- Refractory Multiple Myeloma
- Skin Carcinoma
- Thyroid Gland Carcinoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- ELIGIBILITY CRITERIA FOR SCREENING BIOPSY (STEP 0)
- 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
- Patients 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 patient of childbearing potential is anyone, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria:
- Has achieved menarche at some point
- 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)
- Patients must not expect to conceive or father children by using accepted and
effective method(s) of contraception or by abstaining from sexual intercourse prior
to study entry, for the duration of study participation, and for 4 months after
completion of study; should a patient or partner of the patient become pregnant or
suspect a pregnancy while participating in this study, the treating physician should
be informed 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
- 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 used to
determine patient candidacy for treatment arm assignment
- 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
- 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
- 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
- Patient meets one of the following criteria:
- Patient is a candidate for Z1M based on local Clinical Laboratory
Improvement Act (CLIA) assessment of mismatch repair deficiency
(MMRd) by immunohistochemistry (IHC) or microsatellite instability
(MSI) status by polymerase chain reaction (PCR), adequate tumor
tissue is available for submission for mandatory central screening
IHC and the patient will be able to meet the eligibility criteria for
Z1M within 4 weeks following notification of treatment assignment OR
- The sites 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
- NOTE: There is no particular window of time after receiving the sequencing
report 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
- NOTE: Treatment assignment (and the start of the associated deadline for Step 1
registration) may occur shortly after Step 0 registration. Note that certain
"rare variant" arms require submission of archival tissue for central IHC
testing to determine treatment assignment. For those arms, adequate tissue for
the central IHC is required to be available for submission
- 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
- 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: 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 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 (ANC) >= 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 ULN
- 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)
- NOTE: For patients entering step 0 with assay results from outside laboratories, no
systemic treatment is allowed after step 0 registration
- 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 of a lack of response to the interim treatment
is not required in these cases; however, the following restrictions apply:
- Enrollment onto another investigational therapeutic study is not
permitted
- Patient cannot be responding to interim treatment, since the benefit
of the MATCH treatment is unknown and may deprive patient of an
effective treatment if it were given when a patient is responding to
another 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
- ELIGIBILITY CRITERIA FOR SECOND SCREENING (STEP 2)
- Patient's disease has progressed on Step 1 treatment or patient could not tolerate
assigned treatment
- NOTE: PATIENTS ENTERING STEP 1 WITH A "RARE VARIANT" FROM AN "OUTSIDE" LAB ARE
NOT ELIGIBLE FOR STEP 2
- No response and progression (or inability to tolerate further treatment) occurred <
6 months from start of step 1 treatment
- NOTE: Patients meeting these criteria will NOT be biopsied at this time point;
instead, their step 0 MATCH assay results will be re-interrogated to determine
if another treatment is available upon registration to this study step; it is
not necessary to confirm the availability of another potential treatment
assignment in advance; only aMOIs detected by the MATCH assay may be used for
the determination of eligibility to a relevant subprotocol OR
- Progression (or inability to tolerate further treatment) 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 or bone marrow aspirate for collection and submission of tumor tissue OR
patient will be undergoing a procedure due to medical necessity during which the
tissue may be collected for the central determination of the presence of one or more
of the specific "actionable" mutations/amplifications of interest (aMOI); archived
specimens cannot be accepted
- Patients must meet eligibility criteria as defined in step 0
- Patient must not have been assigned to step 1 treatment based on a "rare variant"
determined by a designated outside laboratory
- ELIGIBILITY CRITERIA FOR SECOND TREATMENT (STEP 3)
- NOTE: If screening biopsy samples were submitted during step 2, 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 3; new non-protocol treatment will NOT be permitted as
intervening therapy after registration to step 2; 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
- ELIGIBILITY CRITERIA FOR THIRD SCREENING (STEP 4)
- Patient's disease has progressed on step 3 treatment or patient could not tolerate
assigned treatment
- Patient must meet one of the following criteria:
- No response and progression (or inability to tolerate further treatment)
occurred < 6 months from start of step 3 (second) treatment AND a biopsy
was performed at step 2 screening
- NOTE: Patients meeting these criteria will NOT be biopsied at this
time point; instead, their latest MATCH assay results will be
re-interrogated to determine if another treatment is available upon
registration to this study step; it is not necessary to confirm the
availability of another potential treatment assignment in advance OR
- Progression (or inability to tolerate further treatment) occurred on step
3 treatment and a biopsy was not performed at step 2 screening
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Other
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Subprotocol A (EGFR activating mutation) |
Patients with EGFR activating mutation receive afatinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients may also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study. |
|
|
Experimental Subprotocol B (HER2 activating mutation) |
Patients with HER2 activating mutation receive afatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol C1 (MET amplification) |
Patients with MET amplification receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation and collection of blood samples throughout the study. Patients may undergo biopsy at screening, on study, and/or at end of treatment. |
|
|
Experimental Subprotocol C2 (MET exon 14 deletion/mutation) |
Patients with MET exon 14 deletion or other mutations that disrupt exon 14 receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy on study and undergo radiologic evaluation and blood sample collection throughout the study. |
|
|
Experimental Subprotocol E (EGFR T790M or rare activating mutation) |
Patients with EGFR T790M or rare activating mutation receive osimertinib (AZD9291) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO or multigated acquisition scan (MUGA) during screening, and biopsy and collection of blood samples on trial and at end of treatment. |
|
|
Experimental Subprotocol F (ALK translocation) |
Patients with ALK translocation receive crizotinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol G (ROS1 translocation or inversion) |
Patients with ROS1 translocation or inversion receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
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. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol I (PIK3CA mutation) |
Patients with PIK3CA mutation without RAS mutation or PTEN loss receive taselisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol J (HER2 amplification >= 7 copy numbers) |
Patients receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO at screening and end of treatment, and biopsy and collection of blood samples on trial and at end of treatment. |
|
|
Experimental Subprotocol K1 (FGFR amplification) |
Patients with FGFR amplification receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout study. Patients may also undergo blood sample collection and tumor biopsy throughout the trial. |
|
|
Experimental Subprotocol K2 (FGFR mutation or fusion) |
Patients with FGFR mutation or fusion receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT or MRI, and tumor biopsy throughout the study. |
|
|
Experimental Subprotocol L (mTOR mutation) |
Patients with mTOR mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol M (TSC1 or TSC2 mutation) |
Patients with TSC1 or TSC2 mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
|
|
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. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol P (PTEN loss) |
Patients with PTEN loss receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol Q (HER2 amplification) |
Patients with HER2 amplification receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
|
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. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol S1 (NF1 mutation) |
Patients with NF1 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol S2 (GNAQ or GNA11 mutation) |
Patients with GNAQ or GNA11 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol T (SMO or PTCH1 mutation) |
Patients with SMO or PTCH1 mutation receive vismodegib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or nuclear study during screening, tumor biopsy on study and CT scan, MRI and blood sample collection throughout the study. |
|
|
Experimental Subprotocol U (NF2 inactivating mutation) |
Patients with NF2 inactivating mutation receive defactinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation) |
Patients with cKIT exon 9, 11, 13, or 14 mutation receive sunitinib PO QD on days 1-28 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study. |
|
|
Experimental Subprotocol W (FGFR pathway aberrations) |
Patients with FGFR1-3 mutation or translocation receive FGFR Inhibitor AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
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. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol Y (Akt mutation) |
Patients with Akt mutation receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
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. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
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. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
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. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
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 30 minutes on days 1 and 15 for 4 cycles and then on day 1 every 28 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion) |
Patients with NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib (LOXO-101) PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study. |
|
|
Experimental Subprotocol Z1F (PIK3CA mutation) |
Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsies at screening and end of treatment as well as CT or MRI at baseline and repeated every 2 cycles for the first 26 cycles then every 3 cycles thereafter until progressive disease or start of another MATCH treatment step. |
|
|
Experimental Subprotocol Z1G (PTEN loss) |
Patients with PTEN loss receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol Z1H (PTEN mutation) |
Patients with PTEN mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol Z1I (BRCA1 or BRCA2 gene mutation) |
Patients with BRCA1 or BRCA2 gene mutation receive adavosertib PO QD for 5 days for 2 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Subprotocol Z1K (AKT mutation) |
Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
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Experimental Subprotocol Z1L (BRAF fusion, aberration or non-V600 mutation) |
Patients with a BRAF non-V600 mutation or BRAF fusion, or another BRAF aberration receive ulixertinib (BVD-523FB) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
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Experimental Subprotocol Z1M (LAG-3 expression >= 1%) |
Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1.Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
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More Details
- Status
- Active, not recruiting
- Sponsor
- National Cancer Institute (NCI)
Study Contact
Detailed Description
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 38 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. Additionally, patients may undergo a computed tomography (CT) scan, magnetic resonance imaging, and/or radionuclide imaging throughout the trial. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.