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

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ClinicalTrials.gov Identifier: NCT03844620
Recruitment Status : Recruiting
First Posted : February 18, 2019
Last Update Posted : February 18, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Other: Best Practice Other: Laboratory Procedure Other: Quality-of-Life Assessment Other: Questionnaire Administration Drug: Regorafenib Drug: Trifluridine and Tipiracil Hydrochloride Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Study Evaluating Tailoring of Advanced/Metastatic Colorectal Cancer (CRC) Therapy Using Circulating Cell-Free Tumor DNA (ctDNA) (TACT-D)
Actual Study Start Date : January 29, 2019
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : August 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I (ctDNA testing, regorafenib, TAS-102)
Patients undergo ctDNA testing and depending on the results receive either regorafenib PO on days 1-21, TAS-102 PO 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.
Other: Laboratory Procedure
Undergo ctDNA testing
Other Names:
  • Lab Test
  • Lab Tests
  • Laboratory Test
  • Test
  • Tests

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Drug: Regorafenib
Given PO
Other Names:
  • BAY 73-4506
  • Stivarga

Drug: Trifluridine and Tipiracil Hydrochloride
Given PO
Other Names:
  • Lonsurf
  • TAS 102
  • TAS-102
  • Tipiracil Hydrochloride Mixture with Trifluridine
  • Trifluridine/Tipiracil
  • Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102

Active Comparator: Arm II (SOC)
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.
Other: Best Practice
Receive SOC
Other Names:
  • standard of care
  • standard therapy

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Drug: Regorafenib
Given PO
Other Names:
  • BAY 73-4506
  • Stivarga

Drug: Trifluridine and Tipiracil Hydrochloride
Given PO
Other Names:
  • Lonsurf
  • TAS 102
  • TAS-102
  • Tipiracil Hydrochloride Mixture with Trifluridine
  • Trifluridine/Tipiracil
  • Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102




Primary Outcome Measures :
  1. 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 ]
    Number of patients with rise in ctDNA level will be compared to Number of patients with progression of disease on scans.

  2. Treatment-related adverse events (TRAEs) of interest (grade 3/4 toxicity, intolerable grade 2 toxicity, or any toxicity requiring dose reduction) between arms [ Time Frame: First 4 months after treatment initiation ]
    Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. To compare the proportions of patients who have experienced TRAEs of interest within the first 4 months between the two treatment arms, Fisher's exact test will be used.


Secondary Outcome Measures :
  1. Mean patient-reported outcomes (PROs) score as per MD Anderson Symptom Inventory (MDASI-GI) [ Time Frame: Up to 18 months ]
    Mean PROs scores measured by MDASI-GI scales will be compared between arms

  2. Mean patient-reported outcomes (PROs) score as per PRO-CTCAE [ Time Frame: Up to 18 months ]
    Mean PROs scores measured by PRO-CTCAE scales will be compared between arms

  3. Percentage of patients with partial response (PR) [ Time Frame: Up to 18 months ]
    Percentage of patients with PR will be compared between arms

  4. Percentage of patients with stable disease (SD) [ Time Frame: Up to 18 months ]
    Percentage of patients with SD will be compared between arms

  5. Overall survival (OS) [ Time Frame: Up to 18 months ]
    OS will be compared between arms.

  6. Percentage of patients who present with events of special interest (ESIs) [ Time Frame: Up to 18 months ]
    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

  7. Cost measured in US dollars [ Time Frame: Up to 18 months ]
    Cost measured in US dollars will be compared between arms

  8. Median time to performance status deterioration [ Time Frame: Up to 18 months ]
    Will be compared between arms.

  9. Median time to PRO deterioration [ Time Frame: Up to 18 months ]
    Will be compared between arms.

  10. Proportion of patients referred to clinical trial [ Time Frame: Up to 18 months ]
    Will be compared in both arms.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03844620


Contacts
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Contact: Kanwal Raghav 713-792-2828 kpraghav@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Kanwal P. Raghav    713-792-2828      
Principal Investigator: Kanwal P. Raghav         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Kanwal Raghav M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03844620     History of Changes
Other Study ID Numbers: 2018-0233
NCI-2019-00246 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2018-0233 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: February 18, 2019    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Trifluridine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents