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

• ClinicalTrials.gov Identifier: NCT04786600
• Recruitment Status: Recruiting
• First Posted: March 8, 2021
• Last Update Posted: December 27, 2021
• Sponsor: University of Florida
• Collaborator: Natera, Inc.
• Information provided by (Responsible Party): University of Florida

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Colorectal Cancer	Device: Signatera ctDNA assay; Drug: pre-specified sequence of FDA-approved drugs and drug combinations	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized Therapeutic Optimization Trial for Subjects With Refractory Metastatic Colorectal Cancer Using ctDNA: Rapid 1 Trial
• Actual Study Start Date: November 4, 2021
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: May 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: ctDNA assay-guided intervention; 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; Subjects will be tested with the Signatera ctDNA assay every 2 weeks.; Drug: pre-specified sequence of FDA-approved drugs and drug combinations; Subjects will receive treatment with a pre-specified sequence of FDA-approved drugs and drug combinations
Active Comparator: Scan-guided Intervention; 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; Subjects will receive treatment with a pre-specified sequence of FDA-approved drugs and drug combinations

Outcome Measures

Primary Outcome Measures :

1. Overall survival [ Time Frame: 1 year ]
   Compare the overall survival in subjects who receive ctDNA assay-guided treatment and scan-guided treatment

Secondary Outcome Measures :

1. Progression free survival [ Time Frame: 1 year ]
   Compare the progression free survival in subjects who receive ctDNA assay-guided treatment and scan-guided treatment
2. Best overall response [ Time Frame: 1 year ]
   Compare the proportion of subjects having each category of response during study participation (complete response, partial response, stable disease, and progressive disease) per RECIST v1.1 criteria

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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. 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 business 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
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; if liver metastases present, then AST and ALT must be ≤ 5 x ULN
  • Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 59 mL/min/1.73m using Cockcroft-Gault equation
• Subjects must not have more than one active malignancy at the time of enrollment (Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen [as determined by the treating physician and approved by the PI] may be included).
• 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

Contacts and Locations

Contacts

Contact: Alexandra Mueller, MS; 352-273-9785; PMO@cancer.ufl.edu

Locations

United States, Florida

University of Florida; Recruiting

Gainesville, Florida, United States, 32608

Contact: Jack Bates 352-265-5121 jbates1@ufl.edu

Sponsors and Collaborators

University of Florida

Natera, Inc.

Investigators

• Principal Investigator: Sherise Rogers, MD; University of Florida

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT04786600
• Other Study ID Numbers: UF-STO-GI-012; UF-STO-GI-012 ( Other Identifier: University of Florida ); IRB202100341 ( Other Identifier: University of Florida ); OCR40199 ( Other Identifier: University of Florida )
• First Posted: March 8, 2021
• Last Update Posted: December 27, 2021
• Last Verified: December 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Florida:

metastatic colorectal cancer; precision oncology; personalized medicine; ctDNA

Additional relevant MeSH terms:

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