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

NCT04786600

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase II Randomized Therapeutic Optimization Trial for Subjects With Refractory Metastatic Cancers Using ctDNA: Rapid 1 Trial
  • Official Title: A Phase II Randomized Therapeutic Optimization Trial for Subjects With Refractory Metastatic Cancers Using ctDNA: Rapid 1 Trial

Clinical Trial IDs

  • ORG STUDY ID: UF-STO-GI-012
  • SECONDARY ID: UF-GI-012
  • SECONDARY ID: IRB202100341
  • SECONDARY ID: OCR40199
  • NCT ID: NCT04786600

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
pre-specified sequence of FDA-approved drugs and drug combinationsScan-guided Intervention

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ctDNA assay-guided interventionExperimentalSubjects 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.
  • pre-specified sequence of FDA-approved drugs and drug combinations
Scan-guided InterventionActive ComparatorSubjects 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.
  • pre-specified sequence of FDA-approved drugs and drug combinations

Eligibility 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

          -  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.

        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
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:1 year
Safety Issue:
Description:Compare the overall survival in subjects who receive ctDNA assay-guided treatment and scan-guided treatment

Secondary Outcome Measures

Measure:Progression free survival
Time Frame:1 year
Safety Issue:
Description:Compare the progression free survival in subjects who receive ctDNA assay-guided treatment and scan-guided treatment
Measure:Best overall response
Time Frame:1 year
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Florida

Trial Keywords

  • metastatic colorectal cancer
  • precision oncology
  • personalized medicine
  • ctDNA

Last Updated

June 7, 2021