Back to resultsCirculating Cell-Free Tumor DNA Testing in Guiding Treatment for Patients With Advanced or Metastatic Colorectal Cancer
Primary Purpose
Refractory Colorectal Carcinoma, Stage III Colorectal Cancer AJCC v8, Stage IIIA Colorectal Cancer AJCC v8
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Best Practice
Laboratory Procedure
Quality-of-Life Assessment
Questionnaire Administration
Regorafenib
Trifluridine and Tipiracil Hydrochloride
Sponsored by
About this trial
This is an interventional treatment trial for Refractory Colorectal Carcinoma
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.
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm I (ctDNA testing, regorafenib, TAS-102)
Arm II (SOC)
Arm Description
Patients 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.
Patients 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.
Outcomes
Primary Outcome Measures
Early change in circulating tumor-derived deoxyribonucleic acid (DNA) (ctDNA) as a predictor of radiographic progression (Arm II-SOC)
Number of patients with rise in ctDNA level will be compared to Number of patients with progression of disease on scans.
Treatment-related adverse events (TRAEs) of interest (grade 3/4 toxicity, intolerable grade 2 toxicity, or any toxicity requiring dose reduction) between arms
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
Mean patient-reported outcomes (PROs) score as per MD Anderson Symptom Inventory (MDASI-GI)
Mean PROs scores measured by MDASI-GI scales will be compared between arms
Mean patient-reported outcomes (PROs) score as per PRO-CTCAE
Mean PROs scores measured by PRO-CTCAE scales will be compared between arms
Percentage of patients with partial response (PR)
Percentage of patients with PR will be compared between arms
Percentage of patients with stable disease (SD)
Percentage of patients with SD will be compared between arms
Overall survival (OS)
OS will be compared between arms.
Percentage of patients who present with events of special interest (ESIs)
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
Cost measured in US dollars
Cost measured in US dollars will be compared between arms
Median time to performance status deterioration
Will be compared between arms.
Median time to PRO deterioration
Will be compared between arms.
Proportion of patients referred to clinical trial
Will be compared in both arms.
Full Information
NCT ID
NCT03844620
First Posted
February 1, 2019
Last Updated
July 21, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03844620
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)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 29, 2019 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm I (ctDNA testing, regorafenib, TAS-102)
Arm Type
Experimental
Arm Description
Patients 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.
Arm Title
Arm II (SOC)
Arm Type
Active Comparator
Arm Description
Patients 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.
Intervention Type
Other
Intervention Name(s)
Best Practice
Other Intervention Name(s)
standard of care, standard therapy
Intervention Description
Receive SOC
Intervention Type
Other
Intervention Name(s)
Laboratory Procedure
Other Intervention Name(s)
Lab Test, Lab Tests, Laboratory Test, Test, Tests
Intervention Description
Undergo ctDNA testing
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Intervention Type
Drug
Intervention Name(s)
Regorafenib
Other Intervention Name(s)
BAY 73-4506, Stivarga
Intervention Description
Given by mouth
Intervention Type
Drug
Intervention Name(s)
Trifluridine and Tipiracil Hydrochloride
Other Intervention Name(s)
Lonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine, Trifluridine/Tipiracil, Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102
Intervention Description
Given by mouth
Primary Outcome Measure Information:
Title
Early change in circulating tumor-derived deoxyribonucleic acid (DNA) (ctDNA) as a predictor of radiographic progression (Arm II-SOC)
Description
Number of patients with rise in ctDNA level will be compared to Number of patients with progression of disease on scans.
Time Frame
First 4 months after treatment initiation
Title
Treatment-related adverse events (TRAEs) of interest (grade 3/4 toxicity, intolerable grade 2 toxicity, or any toxicity requiring dose reduction) between arms
Description
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.
Time Frame
First 4 months after treatment initiation
Secondary Outcome Measure Information:
Title
Mean patient-reported outcomes (PROs) score as per MD Anderson Symptom Inventory (MDASI-GI)
Description
Mean PROs scores measured by MDASI-GI scales will be compared between arms
Time Frame
Up to 18 months
Title
Mean patient-reported outcomes (PROs) score as per PRO-CTCAE
Description
Mean PROs scores measured by PRO-CTCAE scales will be compared between arms
Time Frame
Up to 18 months
Title
Percentage of patients with partial response (PR)
Description
Percentage of patients with PR will be compared between arms
Time Frame
Up to 18 months
Title
Percentage of patients with stable disease (SD)
Description
Percentage of patients with SD will be compared between arms
Time Frame
Up to 18 months
Title
Overall survival (OS)
Description
OS will be compared between arms.
Time Frame
Up to 18 months
Title
Percentage of patients who present with events of special interest (ESIs)
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
Time Frame
Up to 18 months
Title
Cost measured in US dollars
Description
Cost measured in US dollars will be compared between arms
Time Frame
Up to 18 months
Title
Median time to performance status deterioration
Description
Will be compared between arms.
Time Frame
Up to 18 months
Title
Median time to PRO deterioration
Description
Will be compared between arms.
Time Frame
Up to 18 months
Title
Proportion of patients referred to clinical trial
Description
Will be compared in both arms.
Time Frame
Up to 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kanwal Raghav
Phone
713-792-2828
Email
kpraghav@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kanwal Raghav
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kanwal P. Raghav
Phone
713-792-2828
First Name & Middle Initial & Last Name & Degree
Kanwal P. Raghav
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website
Learn more about this trial
Circulating Cell-Free Tumor DNA Testing in Guiding Treatment for Patients With Advanced or Metastatic Colorectal Cancer
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