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

Sponsor
University of California, Irvine (Other)
Overall Status
Recruiting
CT.gov ID
NCT04920032
Collaborator
Taiho Pharmaceutical Co., Ltd. (Industry), Natera, Inc. (Industry)
22
Enrollment
1
Location
1
Arm
34.1
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 1b, prospective, single arm, non-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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

Treatment on study will be administered in 14 day cycles.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
22 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Proof of Concept Study of ctDNA Guided Change in Treatment for Refractory Minimal Residual Disease in Colon Adenocarcinomas
Actual Study Start Date :
Aug 26, 2021
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Jun 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: TASIRI

Patients 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.

Drug: TAS-102
Given PO
Other Names:
  • LONSURF
  • trifluoridine and tipiracil

    • Drug: Irinotecan
    Given IV
    Other Names:
  • CAMPTOSAR
  • CPT-11

    • Combination Product: Standard Treatment
    6 cycles for a 2-week regimen (infusional 5FU based) and up to 4 cycles for a 3-week regimen (oral capecitabine based) after randomization

    Diagnostic Test: Signatera MRD ctDNA Assay
    To be performed within 6-8 weeks of Cycle 1 Day 1. A Mid-treatment ctDNA is to be completed within 6 - 8 weeks of starting treatment. ctDNA is to also be completed within four weeks after completion of study treatment (+/- two weeks)

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of ctDNA positivity in treatment cohort after 6 cycles or at least 3 months of adjuvant treatment [6 months]

      Percent of patients positive for ctDNA after 6 cycles or at least 3 months 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

    1. Percentage of Grade 3-5 Adverse Events [8 weeks]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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, Stage III, or Stage IV colorectal cancer after curative intent resection eligible for adjuvant doublet chemotherapy for at least 3 months.

    3. Must have ctDNA positive assay (tested by Signatera MRD assay) after at least 3 months of perioperative 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:

    8. leukocytesL ≥ 3,000/mcL

    9. absolute neutrophil count: ≥ 1,500/mcL

    10. platelets: ≥ 80,000/mcl

    11. total bilirubin: within normal institutional limits

    12. AST(SGOT)/ALT(SPGT): ≤ 3 X institutional upper limit of normal or ≤ 5 X if liver metastases are present

    13. creatinine: <1.5 X ULN

    14. 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.

    1. 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).

    1. Ability to swallow tablets

    2. 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. -

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Chao Family Comprehensive Cancer Center, University of California, Irvine Orange California United States 92868

    Sponsors and Collaborators

    • University of California, Irvine
    • Taiho Pharmaceutical Co., Ltd.
    • Natera, Inc.

    Investigators

    • Principal Investigator: Farshid Dayyani, MD, PhD, Chao Family Comprehensive Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Farshid Dayyani, Associate Clinical Professor of Medicine, University of California, Irvine
    ClinicalTrials.gov Identifier:
    NCT04920032
    Other Study ID Numbers:
    • UCI 20-43 [HS# 2020-6152]
    • 2020-6152
    First Posted:
    Jun 9, 2021
    Last Update Posted:
    May 31, 2022
    Last Verified:
    May 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:
    Adenocarcinoma
    Neoplasm, Residual
    Irinotecan

    Study Results

    No Results Posted as of May 31, 2022