SX-682 and Nivolumab for the Treatment of RAS-Mutated, MSS Unresectable or Metastatic Colorectal Cancer, the STOPTRAFFIC-1 Trial
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|ClinicalTrials.gov Identifier: NCT04599140|
Recruitment Status : Recruiting
First Posted : October 22, 2020
Last Update Posted : February 21, 2021
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colon Adenocarcinoma Metastatic Colorectal Carcinoma Metastatic Rectal Adenocarcinoma Stage III Colon Cancer AJCC v8 Stage III Rectal Cancer AJCC v8 Stage IIIA Colon Cancer AJCC v8 Stage IIIA Rectal Cancer AJCC v8 Stage IIIB Colon Cancer AJCC v8 Stage IIIB Rectal Cancer AJCC v8 Stage IIIC Colon Cancer AJCC v8 Stage IIIC Rectal Cancer AJCC v8 Stage IV Colon Cancer AJCC v8 Stage IV Rectal Cancer AJCC v8 Stage IVA Colon Cancer AJCC v8 Stage IVA Rectal Cancer AJCC v8 Stage IVB Colon Cancer AJCC v8 Stage IVB Rectal Cancer AJCC v8 Stage IVC Colon Cancer AJCC v8 Stage IVC Rectal Cancer AJCC v8 Unresectable Colon Adenocarcinoma Unresectable Rectal Adenocarcinoma||Drug: CXCR1/2 Inhibitor SX-682 Biological: Nivolumab||Phase 1 Phase 2|
I. To determine the safety profile of CXCR1/2 Inhibitor SX-682 (SX-682) alone and in combination with nivolumab in subjects with refractory RAS mutated microsatellite stable (MSS) metastatic colorectal cancer (mCRC), including the maximum dose that can be administered until adverse effects prevent further dose increases (i.e., the maximum tolerated dose [MTD] or recommended phase 2 dose), and the dose-limiting toxicity (DLT).
I. Evaluate the efficacy of SX-682 in combination with nivolumab on the basis of the objective response rate (ORR), the duration of response, and the rate of progression.
II. Characterize the single-dose and multidose pharmacokinetic (PK) profile of SX-682.
I. Assess overall survival (OS). II. Explore potential biomarkers associated with pharmacodynamic and clinical response to SX-682 alone and combined with nivolumab, where the biomarker measures include, but are not limited to, tumor CMS4, gene expression, deoxyribonucleic acid (DNA) mutations (KRAS, NRAS and BRAF mutation status via ribonucleic acid [RNA] and DNA sequencing), IRF2 (interferon regulatory factor 2) expression, lymphocyte clonality (via sequencing), myeloid-derived suppressor cell (MDSCs), regulatory T-cells (Tregs) and CD69/CD8 T cells, and in the circulation, circulating tumor DNA (ctDNA), T- and B-cell subpopulations, neutrophils, the neutrophil-to-lymphocyte ratio (NLR), MDSCs, Tregs, the CD4:CD8 ratio, chemokines and cytokines.
OUTLINE: This is a phase I, dose-escalation study of CXCR1/2 Inhibitor SX-682, followed by a phase II study.
MONOTHERAPY STAGE: Patients receive SX-682 orally (PO) twice daily (BID) on days 1-21 in the absence of disease progression or unacceptable toxicity.
COMBINATION STAGE: Patients receive SX-682 PO BID on days 1-56 and nivolumab intravenously (IV) over 30 minutes on days 1 and 29. Treatment repeat every 56 days weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study, patients with no have tumor response are followed up every 3 weeks for 90 days, and patients with tumor response every 3 months for up to 6 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||53 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib/II Trial of SX-682 in Combination With Nivolumab for Refractory RAS Mutated (RAS) Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC) (STOPTRAFFIC-1)|
|Actual Study Start Date :||October 14, 2020|
|Estimated Primary Completion Date :||January 31, 2024|
|Estimated Study Completion Date :||January 31, 2024|
Experimental: Treatment (SX-682, nivolumab)
MONOTHERAPY STAGE: Patients receive SX-682 orally PO BID on days 1-21 in the absence of disease progression or unacceptable toxicity.
COMBINATION STAGE: Patients receive SX-682 PO BID on days 1-56 and nivolumab IV over 30 minutes on days 1 and 29. Treatment repeat every 56 days weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Drug: CXCR1/2 Inhibitor SX-682
- Incidence of adverse events (AEs) [ Time Frame: Up to 2 years ]For each system organ class and preferred term, summaries will be made with respect to the number and proportion of subjects having at least 1 occurrence of an adverse event during the study. The incidence of AEs will be presented overall, by system organ class and preferred term, intensity (based on National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0), immune-related adverse events, treatment-emergent adverse events, and additional grouping by severity and relationship to study drug. Individual listings of adverse events will be provided. Dose limiting toxicities and study drug-related grade >= 2 adverse events will be listed individually.
- Overall response rate (ORR) [ Time Frame: Up to 2 years ]Patient response will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Unconfirmed responses will not be used in the final analysis. ORR is defined by the number of (partial response + complete response)/ (total number of treated patients) in the cohort. Will estimate the response rate along with the two-sided exact 95% confidence interval.
- Progression-free survival (PFS) [ Time Frame: Up to 104 weeks ]Assessed according to RECIST 1.1. Median PFS and 95% confidence intervals will be estimated using the Kaplan-Meier method.
- Overall survival (OS) [ Time Frame: Up to 104 weeks ]OS time will be presented using the Kaplan-Meier method. Median OS with 95% confidence interval will be estimated using the Kaplan-Meier method.
- Biomarker analysis [ Time Frame: Up to 2 years ]Summary statistics will be tabulated for CMS4, interferon regulatory factor 2 expression, lymphocyte clonality (via sequencing), myeloid-derived suppressor cells , regulatory T-cells and CD69/CD8 T cells, and in the circulation, circulating tumor deoxyribonucleic acid T- and B-cell subpopulations, neutrophils, the neutrophil-to-lymphocyte ratio, the CD4:CD8 ratio, KRAS, NRAS and BRAF status. Paired t-test or Wilcoxon signed rank test will be used to assess the changes in biomarkers pre and post-treatment. The differences in biomarker levels between responders and non-responders will be assessed using X2 or Fisher's exact test as appropriate. The correlation between biomarker mutation statuses will be assessed using Paired t-test or Wilcoxon signed rank test. Differences in biomarker levels will be assessed using X2 or Fisher's exact test.
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): NCT04599140
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Benny Johnson, DO 713-792-2330 email@example.com|
|Principal Investigator: Benny Johnson, DO|
|Principal Investigator:||Benny Johnson||M.D. Anderson Cancer Center|