Testing Crizotinib as a Potential Targeted Treatment in Cancers With ROS1 Genetic Changes (MATCH-Subprotocol G)

Sponsor: National Cancer Institute (NCI)

Sponsor score: 0

ClinicalTrials ID:NCT04439253

This phase II trial evaluates crizotinib's efficacy in patients with ROS1 translocation cancers. Primary focus is on objective response rates, with secondary goals including progression-free survival and biomarker identification. Patients receive crizotinib orally twice daily in 28-day cycles. Eligibility requires ROS1 gene alteration and a normal ECG.

Patient Parameters

Program Overview

This phase II MATCH treatment trial identifies the effects of crizotinib in patients whose cancer has a genetic change called ROS1 translocation. Crizotinib may block a protein called ROS1, which may be needed for cancer cell growth. Researchers hope to learn if crizotinib will shrink this type of cancer or stop its growth.

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:

Patients receive crizotinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Eligibility Criteria

Inclusion Criteria

  • Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
  • Patients must be positive for translocation or inversion events involving the ROS1 gene via the MATCH Master Protocol
  • Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)

Exclusion Criteria

  • Patients must not have NSCLC with ROS1 rearrangements
  • Patients with a history of interstitial lung disease or pneumonitis are excluded
  • Patients must not have known hypersensitivity to crizotinib or compounds of similar chemical or biologic composition
  • Patients using drugs or foods that are known potent CYP3A4 inhibitors or inducers will be excluded
  • Patients must not have had prior therapy with any ROS1 inhibitor including crizotinib, ceritinib, foretinib, cabozantinib, AP26113, ASP3026, WZ-5-126, TAE684, KIST301072, KIST301080, AZD1480, PF-06463922, RXDX-101 and PF-3922

Locations

FACILITYZIPCITYSTATE
ECOG-ACRIN Cancer Research Group19103PhiladelphiaPennsylvania

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