Clinical Trials /

Study of ctDNA Guided Change in Tx for Refractory Minimal Residual Disease in Colon Adenocarcinomas

NCT04920032

Description:

This is a phase 2, prospective, two-arm, randomized, open-label clinical trial determining the efficacy of adjuvant trifluridine and tipiracil (TAS-102) in combination with irinotecan in patients with ctDNA positive colon adenocarcinoma.

Related Conditions:
  • Colon Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of ctDNA Guided Change in Tx for Refractory Minimal Residual Disease in Colon Adenocarcinomas
  • Official Title: Proof of Concept Study of ctDNA Guided Change in Treatment for Refractory Minimal Residual Disease in Colon Adenocarcinomas

Clinical Trial IDs

  • ORG STUDY ID: UCI 20-43 [HS# 2020-6152]
  • SECONDARY ID: 2020-6152
  • NCT ID: NCT04920032

Conditions

  • Colon Adenocarcinoma
  • Colorectal Cancer

Interventions

DrugSynonymsArms
TAS-102LONSURF, trifluoridine and tipiracilTASIRI
IrinotecanCAMPTOSAR, CPT-11TASIRI

Purpose

This is a phase 2, prospective, two-arm, randomized, open-label clinical trial determining the efficacy of adjuvant trifluridine and tipiracil (TAS-102) in combination with irinotecan in patients with ctDNA positive colon adenocarcinoma.

Detailed Description

      Treatment on study will be administered in 14 day cycles.
    

Trial Arms

NameTypeDescriptionInterventions
TASIRIExperimentalPatients randomized to the experimental arm ("TASIRI") will be treated with TAS-102 25mg/m2 p.o. on days 1-5 and irinotecan 180mg/m2 i.v. on day 1 every 14 days. If ANC <1500/uL on day 1 of a cycle, then G-CSF will be added on day 6 for three days.
  • TAS-102
  • Irinotecan
Standard ArmActive ComparatorPatients randomized to the standard arm (i.e. continuation of the original regimen) are managed per investigator's discretion. Based on tolerability, the goal in the standard arm should be to complete a total of six months of adjuvant treatment.

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Patients must have histologically or cytologically confirmed adenocarcinoma of the
                 colon (high rectal cancer is eligible if resected and no radiation needed). Other
                 histologies which are treated per NCCN guidelines for adjuvant colon cancer are
                 eligible.
    
              2. Must have Stage II or Stage III colorectal cancer eligible for adjuvant doublet
                 chemotherapy for 6 months.
    
              3. Must have ctDNA positive assay (tested by Signatera MRD assay) after 3 months of
                 adjuvant chemotherapy
    
              4. Age ≥ 18 years
    
              5. Performance status: ECOG performance status ≤2
    
              6. Life expectancy of greater than 3 months
    
              7. Adequate organ and marrow function as defined below:
    
                   1. leukocytesL ≥ 3,000/mcL
    
                   2. absolute neutrophil count: ≥ 1,500/mcL
    
                   3. platelets: ≥ 80,000/mcl
    
                   4. total bilirubin: within normal institutional limits
    
                   5. AST(SGOT)/ALT(SPGT): ≤ 3 X institutional upper limit of normal or ≤ 5 X if liver
                      metastases are present
    
                   6. creatinine: <1.5 X ULN
    
              8. The effects of TAS-102 on the developing human fetus at the recommended therapeutic
                 dose are unknown. For this reason and because topoisomerase inhibitors are known to be
                 teratogenic, women of child-bearing potential and men must agree to use adequate
                 contraception (hormonal or barrier method of birth control; abstinence) prior to study
                 entry, for the duration of study participation, and for 90 days following completion
                 of therapy. Should a woman become pregnant or suspect she is pregnant while
                 participating in this study, she should inform her treating physician immediately.
    
                 a. A female of child-bearing potential is any woman (regardless of sexual orientation,
                 having undergone a tubal ligation, or remaining celibate by choice) who meets the
                 following criteria:
    
                   -  Has not undergone a hysterectomy or bilateral oophorectomy; or
    
                   -  Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
                      has had menses at any time in the preceding 12 consecutive months).
    
              9. Ability to swallow tablets
    
             10. Ability to understand and the willingness to sign a written informed consent.
    
            Exclusion Criteria:
    
              1. Patients who have had major surgery within 4 weeks, or chemotherapy or radiotherapy
                 within 2 weeks prior to Cycle 1 Day 1
    
              2. All toxicities attributed to prior anti-cancer therapy other than alopecia must have
                 resolved to grade 1 or baseline
    
              3. Patients may not be receiving any other investigational agents.
    
              4. Patients with known metastases.
    
              5. History of allergic reactions attributed to compounds of similar chemical or biologic
                 composition to TAS-102, irinotecan or other agents used in study.
    
              6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
                 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
                 arrhythmia, or psychiatric illness/social situations that would limit compliance with
                 study requirements.
    
              7. Prior treatment with irinotecan or TAS-102.
    
              8. History of another primary cancer within the last 3 years with the exception of
                 non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical
                 carcinoma in-situ.
    
              9. Inability to comply with study and follow-up procedures as judged by the Investigator
    
             10. Patients who are pregnant or nursing due to the potential for congenital abnormalities
                 and the potential of this regimen to harm nursing infants. -
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Percentage of ctDNA positivity in treatment cohort at 6 months of adjuvant treatment
    Time Frame:6 months
    Safety Issue:
    Description:Percent of patients positive for ctDNA at 6 months after starting adjuvant treatment will be used to estimate the efficacy of adjuvant trifluridine and tipiracil (TAS102) in combination with irinotecan in patients with ctDNA positive colon adenocarcinoma. The Signatera MRD ctDNA Assay will be used to measure ctDNA positivity.

    Secondary Outcome Measures

    Measure:Percentage of Grade 3-5 Adverse Events
    Time Frame:8 weeks
    Safety Issue:
    Description:To evaluate the tolerability of drug-related grade 3-5 adverse events in patients with ctDNA positive colon adenocarcinoma. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:University of California, Irvine

    Last Updated

    June 9, 2021