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: November 21, 2022
• Sponsor: University of Florida
• Collaborator: Natera, Inc.
• Information provided by (Responsible Party): University of Florida

Tracking Information

• First Submitted Date: March 4, 2021
• First Posted Date: March 8, 2021
• Last Update Posted Date: November 21, 2022
• Actual Study Start Date: November 4, 2021
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 4, 2021)

Overall survival [ Time Frame: 1 year ]

Compare the overall survival in subjects who receive ctDNA assay-guided treatment and scan-guided treatment

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 4, 2021)

• Progression free survival [ Time Frame: 1 year ]
  Compare the progression free survival in subjects who receive ctDNA assay-guided treatment and scan-guided treatment
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase II Randomized Therapeutic Optimization Trial for Subjects With Refractory Metastatic Colorectal Cancer Using ctDNA: Rapid 1 Trial
• Official Title: A Phase II Randomized Therapeutic Optimization Trial for Subjects With Refractory Metastatic Colorectal Cancer Using ctDNA: Rapid 1 Trial
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Colorectal Cancer

Intervention

• 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

Study Arms

• 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.
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 4, 2021): 78
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2025
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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
  • 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: 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 )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Florida
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Florida
• Original Study Sponsor: Same as current
• Collaborators: Natera, Inc.

Investigators

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

• PRS Account: University of Florida
• Verification Date: November 2022