A Phase II Randomized Therapeutic Optimization Trial for Subjects With Refractory Metastatic Colorectal Cancer Using ctDNA: Rapid 1 Trial

NCT04786600 | Terminated Phase 2 Results DMC FDA Device

• 3 other identifiers: UF-STO-GI-012IRB202100341OCR40199
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancer; precision oncology; personalized medicine; ctDNA

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Determine the overall survival

  580 days

Secondary Outcomes (2)

• Best Overall Treatment Response

  1 year

• Progression-free Survival

  6 months

Study Arms (2)

ctDNA assay-guided intervention

EXPERIMENTAL

Subjects 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.

Device: Signatera ctDNA assay; Drug: pre-specified sequence of FDA-approved drugs and drug combinations

Scan-guided Intervention

ACTIVE COMPARATOR

Subjects 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.

Drug: pre-specified sequence of FDA-approved drugs and drug combinations

Interventions

Signatera ctDNA assay DEVICE

Subjects will be tested with the Signatera ctDNA assay every 2 weeks.

ctDNA assay-guided intervention

pre-specified sequence of FDA-approved drugs and drug combinations DRUG

Subjects will receive treatment with a pre-specified sequence of FDA-approved drugs and drug combinations

Scan-guided Intervention; ctDNA assay-guided intervention

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A histologic confirmed adenocarcinoma of the colon or rectum with RECIST measurable metastatic disease measurable and not currently a candidate for oligometastatic definitive management
• Must have at least received first-line oxaliplatin-based therapy for metastatic disease, or a clinically acceptable and documented reason they did not, and progressed or were intolerant to the therapy. Individuals who recurred within 6 months of completion of oxaliplatin based adjuvant chemotherapy are also eligible. Subjects may enroll at any line of therapy past this first line so long as the patient's next clinically reasonable prescribed treatment would be Folfiri + Bevacizumab/biosimilar, Anti-EGFR therapy (with or without irinotecan), OR Lonsurf.
• Subjects must have tissue from either the primary and/or metastatic deposit available for submission at enrollment. Tissue can be from either a biopsy or resection surgery, whichever is most recent, but must be from the past five years.
• Subjects must have tissue and blood shipped to Natera no fewer than 10 days prior to starting treatment.
• 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, as defined as:
• Absolute neutrophil count (ANC) ≥ 1,500/µL
• Hemoglobin ≥ 9g/dL
• Platelets ≥ 100,000/µL
• Total bilirubin ≤ 1.5 ULN or direct bilirubin ≤ 1 x ULN

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead
• Natera, Inc.: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32608, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Drug Combinations

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Results Point of Contact

• Title: Allison Allegra
• Organization: University of Florida

allisonallegra3@ufl.edu

352-294-5691

Study Officials

• Sherise Rogers, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 8, 2021
• Study Start: March 14, 2022
• Primary Completion: March 19, 2024
• Study Completion: March 19, 2024
• Last Updated: July 1, 2025
• Results First Posted: July 1, 2025

Record last verified: 2025-06

Locations

US (1)