Protocol No.: OCR40199
Sponsor Protocol No.: UF-GI-012
Protocol Title.: A Phase II Randomized Therapeutic Optimization Trial for Subjects With Refractory Metastatic Colorectal Cancer Using ctDNA: Rapid 1 Trial
Principal Investigator: Rogers, Sherise
Objective: This randomized, phase 2 study will investigate the use of the Signatera ctDNA assay versus the standard scan-based approach to guide treatment in patients with metastatic colorectal cancer. The aim of this study will be to measure and compare the overall survival, progression-free survival, and best overall response while on study of patients whose treatment has been guided by these two approaches.
Phase: Phase II
Age Group: Adult
Age: 18 Years - 99 Years
Experimental: ctDNA assay-guided interventionSubjects on this arm will be tested with the Signatera ctDNA assay while receiving treatment on a pre-specified sequence of FDA-approved drugs and drug combinations. Subjects will move through this sequence based on the results of the ctDNA assay. Subjects will move to a new drug or drug combination in the sequence when the ctDNA assay indicates a significant increase in ctDNA level. Subjects will also have imaging scans every 12 weeks while on each drug or drug combination and subjects will move to a new drug or drug combination if these scans indicate disease progression.
Active Comparator: Scan-guided InterventionSubjects on this arm will be treated with the same pre-specified sequence of FDA-approved drugs and drug combinations as those on the ctDNA assay- guided intervention arm. Subjects will move through the sequence based on the results of imaging scans, moving to a new drug or drug combination if imaging shows progressive disease.
Detailed Eligibility: Inclusion Criteria: - Histologically confirmed adenocarcinoma of the colon or rectum with metastatic disease measurable by RECIST v1.1 and not currently a candidate for oligometastatic definitive management - Must have progressed or have demonstrated intolerance to first line therapy for metastatic disease. Individuals who recurred within 6 months of completion of oxaliplatin based adjuvant chemotherapy are also eligible. - Subjects must have tissue from either the primary and/or metastatic deposit available for submission at enrollment - Subjects must have measurable ctDNA, as detected by the Signatera ctDNA assay at time of sample analysis - Subjects must have had molecular profiling to determine tumor RAS, BRAF and MMR/MSI status - Subjects with known or suspected Gilbert's disease must be formally tested for UGT1A1*28 with results available to study team prior to treatment initiation - Any clinically relevant (as deemed by the PI) adverse events related to prior therapies must have resolved to Grade 1 or less (CTCAE 5.0) at study enrollment - Age ≥18 years - ECOG performance status of 0-2 - Life expectancy of at least 6 months - Adequate organ function - Subjects must not have more than one active malignancy at the time of enrollment - Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 12 weeks after the end of protocol-specified treatment to minimize the risk of pregnancy. - Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods throughout the study and should avoid conceiving children for 12 weeks following the last dose of the protocol-specified treatment. - Written informed consent obtained from the subject and the subject agrees to comply with all the study related procedures Exclusion Criteria: - Colorectal cancer known to be Microsatellite High (MSI-H), deficient in DNA mismatch repair genes (dMMR), or BRAF (V600E) mutated - Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 12 weeks after the last dose of the protocol-specified treatment - Females who are pregnant or breastfeeding - History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician - Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness - Prior radiation therapy must have been completed 14 days prior to study entry - Prior chemotherapy or biologic therapy must have been completed 21 days prior to study entry - Known Dihydropyrimidine Dehydrogenase (DPD) deficiency