Novel PET/CT Imaging Biomarkers of CB-839 in Combination With Panitumumab and Irinotecan in Patients With Metastatic and Refractory RAS Wildtype Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT03263429|
Recruitment Status : Recruiting
First Posted : August 28, 2017
Last Update Posted : June 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer Metastatic Colorectal Cancer RAS Wild Type Colorectal Cancer Refractory Colorectal Cancer||Drug: Glutaminase Inhibitor CB-839 Biological: Panitumumab Drug: Irinotecan Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacological Study Device: Imaging with 18F-FSPG PET/CT scans||Phase 1 Phase 2|
Primary Objective of Phase I:
• Determine the maximum tolerated dose (MTD) of CB839 in combination with panitumumab and irinotecan
Primary Objective of Phase II:
• Determine the efficacy of CB-839 in combination with panitumumab and irinotecan as measured by the objective response rate (RR) in patients with previously EGFR treated RAS wildtype colorectal adenocarcinoma.
Secondary Objectives of Phase II:
- Determine the disease control rate, progression-free survival, and overall survival (phase II).
- Correlate radiological features of pre- and post-treatment carbon C 11 glutamine (11C-glutamine) positron emission tomography (PET)/computed tomography (CT) and fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) PET/CT with clinical outcome and biological correlates (tissue gene signature, plasma glutamate levels, exosomes). (Phase II).
- Collect pre-treatment biopsy tissue and prospectively correlate clinical outcome with a glutamate-biased gene set. (Phase II)
- Quantify exosomal content in the plasma (Phase II).
• Correlate radiological features of pre- and post-treatment 11C-Glutamine PET/CT and 18F-FSPG PET/CT with clinical outcome. (Phase I)
OUTLINE: This is a dose-escalation study of glutaminase inhibitor CB-839.
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 up at 28 days and then every 3 months for up to 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||August 23, 2017|
|Estimated Primary Completion Date :||September 2020|
|Estimated Study Completion Date :||August 2021|
Patients receive glutaminase inhibitor CB-839 PO BID on days 1-28, panitumumab 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.
Drug: Glutaminase Inhibitor CB-839
Given by mouth
Given by vein
Drug: Irinotecan Hydrochloride
Given by vein
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Device: Imaging with 18F-FSPG PET/CT scans
During phase II at baseline and day 28 of cycle 1
- Maximum tolerated dose (Phase I) B-839 in combination with panitumumab and irinotecan hydrochloride [ Time Frame: Up to 12 months ]The maximum tolerated dose will be determined
- Response rate (Phase II) [ Time Frame: Up to 12 months ]Will use Simon's optimal 2-stage design to monitor efficacy in this trial.
- Recommended phase 2 dose of CB-839 in combination with panitumumab and irinotecan hydrochloride (Phase I) [ Time Frame: Up to 12 months. ]The recommended phase 2 dose will be determined.
- Disease control rate [ Time Frame: Up to 12 months ]The disease control rate will be evaluated.
- Maximum Standardized Uptake Value (SUVmax) of fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) uptake (Phase II) [ Time Frame: Up to 8 weeks ]evaluate the relationship between 18F-FSPG uptake at baseline and change in tumor size at the time of objective response assessment using a standard linear regression analysis. The slope will describe the shape of the relationship between SUVmax and change in tumor size, while the coefficient of determination (R2) describes the strength of the relationship between the two measures. A similar linear regression analysis will be conducted to quantify the relationship between the change in SUVmax as measured from baseline to after one cycle of therapy and change in tumor size.
- Plasma exosomal content (phase II) [ Time Frame: Up to 12 months ]Plasma exosomal content will be assessed at pre-treatment, after one cycle of treatment, and at disease progression.
- Progression free survival (phase II) [ Time Frame: Up to 12 months ]will use Cox proportional hazards model to estimate the association between PET SUVmax and OS.
- Overall Survival [ Time Frame: Up to 12 months ]will use Cox proportional hazards model to estimate the association between PET SUVmax and OS.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03263429
|Contact: Clinical Trials Information Programfirstname.lastname@example.org|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Clinical Trials Information Program 800-811-8480|
|Principal Investigator: Jordan Berlin, MD|
|Principal Investigator:||Jordan Berlin, MD||Vanderbilt-Ingram Cancer Center|