Trials / Completed

CompletedNCT03263429

Novel PET/CT Imaging Biomarkers of CB-839 in Combination With Panitumumab and Irinotecan in Patients With Metastatic and Refractory RAS Wildtype Colorectal Cancer

Phase I/II Study to Evaluate the Safety, Efficacy, and Novel PET/CT Imaging Biomarkers of CB-839 in Combination With Panitumumab and Irinotecan in Patients With Metastatic and Refractory RAS Wildtype Colorectal Cancer

Status: Completed
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 29 (actual)

Sponsor: Vanderbilt-Ingram Cancer Center · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the best dose and side effects of glutaminase inhibitor CB-839 and how well it works with panitumumab and irinotecan hydrochloride (phase I only) in treating patients with RAS wildtype colorectal cancer that has spread to other places in the body and does not respond to treatment. Glutaminase inhibitor CB-839 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving glutaminase inhibitor CB-839 with panitumumab and irinotecan hydrochloride may work better in treating patients with colorectal cancer.

Detailed description

Objectives: Primary Objective of Phase I: • Determine the safety and tolerability of CB-839 in combination with panitumumab and irinotecan. Exploratory Objective of Phase I (Optional Imaging Sub-study): • Correlate radiological features of pre- and post-treatment 11C-Glutamine PET/CT and 18F-FSPG PET/CT with clinical outcome. Primary Objective of Phase II: • Determine the efficacy of CB-839 in combination with panitumumab as measured by the response rate (RR). Secondary Objectives of Phase II: * Determine the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). * Perform the following correlative studies (in the phase 2 component): * Correlate radiological features of pre- and post-treatment 18F-FSPG PET/CT with clinical outcome and biological correlates (tissue gene signature, exosomes). * Collect blood samples during each radiotracer injection to assess pharmacokinetics. * Collect pre-treatment biopsy tissue and prospectively correlate clinical outcome with a glutamine metabolism gene signature. * Quantify exosomal content in the plasma. Exploratory Objective of Phase II: • Development of patient-derived organoids from pre-treatment tissue biopsy OUTLINE: Phase I is a dose-escalation study of glutaminase inhibitor CB-839 in combination with standard doses of panitumumab and irinotecan hydrochloride. Phase II will study efficacy of glutaminase inhibitor CB-839 in combination with standard doses of panitumumab. Patients receive glutaminase inhibitor CB-839 orally (PO) twice daily (BID) on days 1-28, panitumumab intravenously (IV) over 60-90 minutes on days 1 and 15, and irinotecan hydrochloride IV over 90 minutes on day 1 and 15 (Phase I only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 28 days and then every 3 months for up to 1 year.

Conditions

Interventions

Type	Name	Description
DRUG	Glutaminase Inhibitor CB-839	Given by mouth
BIOLOGICAL	Panitumumab	Given by vein
DRUG	Irinotecan Hydrochloride (phase I only)	Given by vein
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DEVICE	Imaging with 11C-Glutamine PET/CT scans and 18F-FSPG PET/CT scans	During phase II at baseline and day 28 of cycle 1

Timeline

Start date: 2017-08-23
Primary completion: 2023-08-15
Completion: 2023-12-21
First posted: 2017-08-28
Last updated: 2024-08-30
Results posted: 2024-08-30

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03263429. Inclusion in this directory is not an endorsement.