Protocol Summary

Protocol No.: OCR13631

Sponsor Protocol No.: EAY131, MATCH

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

Principal Investigator: George, Thomas

Objective: 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.

Description: (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. (Treatment): Patients are assigned to 1 of 24 treatment subprotocols based on molecularly-defined subgroup. (Re-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. (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.

Phase: Phase II

Age Group: Adult

Age: 18 Years - N/A

Gender: All

Scope: National

Treatment:

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.

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.

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.

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.

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.

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.

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.

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.

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.

Experimental: Subprotocol J (HER2 amplification >= 7 copy numbers)
Patients with HER2 amplification >= 7 copy numbers receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Detailed Eligibility:
INCLUSION CRITERIA:
1. Ages 18 years old and older
2. Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma requiring therapy and 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; any other cancer from which the patient has been disease-free for 5 years
3. Patients must have measurable disease
4. 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 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
- Patient will be undergoing a procedure due to medical necessity during which the tissue may be collected
- Formalin-fixed paraffin-embedded (FFPE) tumor tissue block(s) are available for submission following pre-registration (not applicable for bone marrow aspirate specimens); criteria for the submission of FFPE tissue are:
- Tissue must have been collected within 6 months prior to pre-registration
- Patient has not received any intervening therapy that is considered to be targeted (e.g. against a particular or multiple molecular target) for their cancer since the collection of the tumor sample; they may have received cytoxic chemotherapy for up to 4 cycles, but must not have had response to such treatment
- Formalin-fixed paraffin-embedded tumor tissue block(s) must meet the minimum requirements
5. 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)
6. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =7. Patients must not currently be receiving any other investigational agents
** Contact the study team for the full listing of Inclusion and Exclusion criteria.

Applicable Conditions:

  • Bladder Cancer
  • Brain and Nervous System
  • Breast Cancer
  • Colon Cancer
  • Gastrointestinal Cancer
  • Gynecologic Cancer
  • Head & Neck Cancer
  • Kidney Cancer (Renal Cell)
  • Liver Cancer
  • Lung Cancer
  • Lymphoma - Hodgkin
  • Lymphoma - Non-Hodgkin
  • Melanoma
  • Ovarian Cancer
  • Pancreatic Cancer
  • Prostate Cancer
  • Sarcoma
  • Skin Cancer
  • Urologic Cancer
  • Participation Institution:

  • UF Gainesville : Elena Nelson
  • Contact:
    Elena Nelson
    Phone: +1 352-265-0680 ext. 50144
    Email: eab1109@ufl.edu

    More Information: View study listing on ClinicialTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT02465060