Clinical Trials /

Circulating Cell-Free Tumor DNA Testing in Guiding Treatment for Patients With Advanced or Metastatic Colorectal Cancer

NCT03844620

Description:

This phase II trial studies circulating cell-free tumor DNA testing to guide treatment with regorafenib or TAS-102 in patients with colorectal cancer that has spread to other areas of the body. Studying samples of blood from patients with colorectal cancer may help doctors understand how well patients respond to treatment. Regorafenib and TAS-102 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known how well ctDNA testing works in guiding treatment with regorafenib and TAS-102 for patients with advanced or metastatic colorectal cancer.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Circulating Cell-Free Tumor DNA Testing in Guiding Treatment for Patients With Advanced or Metastatic Colorectal Cancer
  • Official Title: A Randomized Study Evaluating Tailoring of Advanced/Metastatic Colorectal Cancer (CRC) Therapy Using Circulating Cell-Free Tumor DNA (ctDNA) (TACT-D)

Clinical Trial IDs

  • ORG STUDY ID: 2018-0233
  • SECONDARY ID: NCI-2019-00246
  • SECONDARY ID: 2018-0233
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03844620

Conditions

  • Refractory Colorectal Carcinoma
  • Stage III Colorectal Cancer AJCC v8
  • Stage IIIA Colorectal Cancer AJCC v8
  • Stage IIIB Colorectal Cancer AJCC v8
  • Stage IIIC Colorectal Cancer AJCC v8
  • Stage IV Colorectal Cancer AJCC v8
  • Stage IVA Colorectal Cancer AJCC v8
  • Stage IVB Colorectal Cancer AJCC v8
  • Stage IVC Colorectal Cancer AJCC v8

Interventions

DrugSynonymsArms
RegorafenibBAY 73-4506, StivargaArm I (ctDNA testing, regorafenib, TAS-102)
Trifluridine and Tipiracil HydrochlorideLonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine, Trifluridine/Tipiracil, Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102Arm I (ctDNA testing, regorafenib, TAS-102)

Purpose

This phase II trial studies circulating cell-free tumor DNA testing to guide treatment with regorafenib or TAS-102 in patients with colorectal cancer that has spread to other areas of the body. Studying samples of blood from patients with colorectal cancer may help doctors understand how well patients respond to treatment. Regorafenib and TAS-102 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known how well ctDNA testing works in guiding treatment with regorafenib and TAS-102 for patients with advanced or metastatic colorectal cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the ability of early change in circulating tumor-derived deoxyribonucleic acid
      (ctDNA) (ctDNA-early dynamic changes [EDC] or A ctDNA) during systemic therapy in metastatic
      colorectal cancer (mCRC) to predict radiographic progression (only standard of care [SOC]
      arm).

      II. To evaluate differences in clinically significant treatment-related adverse events
      (TRAEs) of interest (grade 3/4 toxicity per National Cancer Institute (NCI)-Common
      Terminology Criteria for Adverse Events (CTCAE) version 4.0, intolerable grade 2 toxicity or
      any toxicity requiring dose reduction) between SOC and ctDNA arm.

      SECONDARY OBJECTIVES:

      I. To evaluate differences in patient-reported outcomes (PROs) between SOC and ctDNA arm.

      II. To compare Response Evaluation Criteria in Solid Tumors (RECIST) duration of complete
      response (DCR) (partial response [PR] and stable disease [SD]) between SOC and ctDNA arm.

      III. To evaluate differences in overall survival (OS) between SOC and ctDNA arm.

      IV. To evaluate differences between SOC and ctDNA arm with regards to emergency severity
      indices (ESIs): Hospitalizations/emergency room visits.

      V. To evaluate differences between SOC and ctDNA arm with regards to ESIs: Need for medical
      interventions (blood transfusions and intravenous [IV] hydration).

      VI. To evaluate cost-effectiveness associated with both strategies, i.e. SOC strategy and
      ctDNA strategy in treatment of mCRC.

      VII. To compare time to deterioration of Eastern Cooperative Oncology Group (ECOG)
      performance status (PS) between SOC and ctDNA arms.

      VIII. To compare time to deterioration of PROs between SOC and ctDNA arms. IX. To evaluate
      differences in proportion of patients referred to clinical trial after completion of therapy
      between SOC and ctDNA arms.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients undergo ctDNA testing and depending on the results receive either regorafenib
      orally (PO) on days 1-21, trifluridine and tipiracil hydrochloride (TAS-102) PO twice daily
      (BID) on days 1-5 and 8-12, or regorafenib PO on days 1-21 and TAS-102 PO BID on days 1-5 and
      8-12. Treatment repeats every 28 days in the absence of disease progression or unacceptable
      toxicity.

      ARM II: Patients receive regorafenib or TAS-102 per standard of care. Treatment continues in
      the event of disease stability or regression as per discretion of treating physician or
      absence of disease progression.

      After completion of study treatment, patients are followed up at 2 weeks and then monthly for
      up to 18 months.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (ctDNA testing, regorafenib, TAS-102)ExperimentalPatients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle. Patients in this arm will get ctDNA testing and will continue treatment beyond 1st cycle depending on ctDNA results. Beyond that patients will continue treatment in the absence of disease progression or unacceptable toxicity.
  • Regorafenib
  • Trifluridine and Tipiracil Hydrochloride
Arm II (SOC)Active ComparatorPatients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle as per standard of care. Patients in this arm will continue treatment in the absence of disease progression or unacceptable toxicity.
  • Regorafenib
  • Trifluridine and Tipiracil Hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed colorectal cancer.

          -  Patients must have advanced or metastatic disease with no curative options.

          -  Patients must have radiographically evaluable disease.

          -  Patients must have had at least 2 prior therapies for mCRC (including fluorouracil
             [5-FU], oxaliplatin, irinotecan, bevacizumab; cetuximab/panitumumab [for RAS wild type
             (WT) patients]) and have either progressed on or intolerant to these agents or use of
             these agents is contraindicated.

          -  Patients must be clinically eligible for either regorafenib or TAS-102 as per their
             treating physician.

          -  Patients must have a negative serum pregnancy test done less than are equal to 14 days
             prior to randomization for women of childbearing potential only. 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.

          -  Patients must have ability to complete questionnaire(s) by themselves or with
             assistance.

          -  Patients must have ability to provide informed written consent.

          -  Patients must be willing to return to enrolling institution for follow-up as per study
             schedule.

          -  Patients must be willing to provide blood samples for correlative studies.

          -  Any of the following: Pregnant or nursing women, men or women of childbearing
             potential who are unwilling to employ adequate contraception.

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens.

        Exclusion Criteria:

          -  Patient who have received prior TAS-102 are eligible to enroll on the study if they
             can receive regorafenib and vice-versa. Otherwise these patients will be excluded from
             the study.

          -  Congestive heart failure > New York Heart Association (NYHA) class 2, unstable angina
             (angina symptoms at rest), new-onset angina (begun within the last 3 months) or
             myocardial infarction less than 3 months prior to randomization.

          -  Ongoing infection > grade 2 CTCAE version 4.0.

          -  Symptomatic metastatic brain or meningeal tumors unless the patient is > 3 months from
             definitive therapy, has a negative imaging study within 4 weeks of randomization and
             is clinically stable with respect to brain lesions at the time of randomization (Note:
             patient must not be undergoing acute steroid therapy or taper [chronic steroid therapy
             is acceptable provided that the dose is stable for one month prior to and following
             screening radiographic studies]).

          -  Renal failure requiring hematological or peritoneal dialysis.

          -  Patients unable to swallow oral medications.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Early change in circulating tumor-derived deoxyribonucleic acid (DNA) (ctDNA) as a predictor of radiographic progression (Arm II-SOC)
Time Frame:First 4 months after treatment initiation
Safety Issue:
Description:Number of patients with rise in ctDNA level will be compared to Number of patients with progression of disease on scans.

Secondary Outcome Measures

Measure:Mean patient-reported outcomes (PROs) score as per MD Anderson Symptom Inventory (MDASI-GI)
Time Frame:Up to 18 months
Safety Issue:
Description:Mean PROs scores measured by MDASI-GI scales will be compared between arms
Measure:Mean patient-reported outcomes (PROs) score as per PRO-CTCAE
Time Frame:Up to 18 months
Safety Issue:
Description:Mean PROs scores measured by PRO-CTCAE scales will be compared between arms
Measure:Percentage of patients with partial response (PR)
Time Frame:Up to 18 months
Safety Issue:
Description:Percentage of patients with PR will be compared between arms
Measure:Percentage of patients with stable disease (SD)
Time Frame:Up to 18 months
Safety Issue:
Description:Percentage of patients with SD will be compared between arms
Measure:Overall survival (OS)
Time Frame:Up to 18 months
Safety Issue:
Description:OS will be compared between arms.
Measure:Percentage of patients who present with events of special interest (ESIs)
Time Frame:Up to 18 months
Safety Issue:
Description:Percentage of patients who present with ESIs [described as either Hospitalizations/emergency room visits or need for medical interventions (blood transfusions and IV hydration)] will be compared between arms
Measure:Cost measured in US dollars
Time Frame:Up to 18 months
Safety Issue:
Description:Cost measured in US dollars will be compared between arms
Measure:Median time to performance status deterioration
Time Frame:Up to 18 months
Safety Issue:
Description:Will be compared between arms.
Measure:Median time to PRO deterioration
Time Frame:Up to 18 months
Safety Issue:
Description:Will be compared between arms.
Measure:Proportion of patients referred to clinical trial
Time Frame:Up to 18 months
Safety Issue:
Description:Will be compared in both arms.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

May 5, 2020