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TAS-102, Irinotecan, and Bevacizumab for the Treatment of Pre-treated Metastatic or Unresectable Colorectal Cancer, the TABAsCO Study

Primary Purpose

Advanced Colorectal Carcinoma, Metastatic Colon Adenocarcinoma, Metastatic Rectal Adenocarcinoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Irinotecan
Bevacizumab
Trifluridine and Tipiracil Hydrochloride
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Colorectal Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Advanced colorectal cancer (metastatic or unresectable): Histologically or cytological proven adenocarcinoma of the colon or rectum which is metastatic or otherwise incurable
  • Prior treatment with a fluoropyrimidine (5-fluorouracil [5-FU] or capecitabine) and oxaliplatin in the metastatic/unresectable setting OR, recurrence within 12 months of adjuvant therapy with a regimen that included oxaliplatin
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Hemoglobin >= 9 g/dL
  • Absolute neutrophil count >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Creatinine < 1.5 upper limit of normal (ULN) or if >= 1.5 x ULN creatinine clearance (CRCL) >= 30 mL/min (by Cockcroft-Gault)
  • Bilirubin < 1.5 x ULN
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN or =< 5 x ULN if with hepatic metastases
  • Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

  • Prior treatment with TAS-102 or irinotecan
  • Anti-cancer therapy within 2 weeks of the planned first dose of study medication
  • Unresolved toxicities from prior therapy of > grade 1, excluding alopecia or similar toxicities which are not deemed to be clinically significant or put the participant at greater risk. Grade 2 neuropathy is permitted
  • Major surgery within 4 weeks of anticipated start of therapy
  • Uncontrolled hypertension: systolic blood pressure >= 150, diastolic blood pressure >= 100
  • Unstable angina, symptomatic congestive heart failure or cardiac arrhythmia requiring anti-arrhythmic therapy (beta-blockers, calcium channel blockers and digoxin are allowed)
  • Arterial or venous thrombotic or embolic events within 3 months of study initiation, unless well controlled on stable anti-coagulation for >= 2 weeks. This excludes uncomplicated catheter associated venous thrombosis
  • History of cerebrovascular or myocardial ischemia within 6 months of initiation
  • National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 grade 3 or greater hemorrhage within the past 4 weeks
  • Proteinuria >= 2+, unless 24 hour urine collection demonstrates =< 1 g of protein OR spot protein: creatinine demonstrates a ratio of =< 1
  • Untreated brain metastases
  • History of abnormal glucuronidation of bilirubin (Gilbert's syndrome)
  • History of second primary malignancy within 3 years prior to enrollment, excluding in-situ cervical carcinoma, non-melanoma skin cancer or malignancy of equivalent risk which is highly unlikely to require systemic treatment in the next 2 years
  • Have known active infection which would heighten the risk of complications
  • Pregnant or nursing female participants
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Sites / Locations

  • Moffitt Cancer Center
  • Rutgers Cancer Institute of New Jersey
  • Roswell Park Cancer Institute
  • Fox Chase Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (irinotecan, bevacizumab, TAS-102)

Arm Description

Patients receive irinotecan IV over 90 minutes and bevacizumab IV over 10 minutes on days 1 and 15. Patients also receive trifluridine and tipiracil hydrochloride PO BID on days 2-6 and 16-20. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Median progression free survival (PFS)
Will be assessed via the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 guidelines. The PFS will be summarized using standard Kaplan-Meier methods, where estimates of the median PFS and 6/12-month PFS rates will be obtained with 90% confidence intervals.

Secondary Outcome Measures

Objective response rate (ORR)
ill be tabulated based upon RECIST v1.1 criteria. Will be summarized using frequencies and relative frequencies. Using Jeffrey's prior method, a 90% confidence interval about the true ORR will be obtained for each treatment group.
Median overall survival (OS)
OS will be summarized using standard Kaplan-Meier methods; where estimates of the median survival and 12-month rates are obtained with 90% confidence intervals
Disease-specific survival (DSS)
DSS will be summarized using standard Kaplan-Meier methods; where estimates of the median survival and 12-month rates are obtained with 90% confidence intervals.
Aggregate rates of adverse events
easured by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and recorded to objectively measure toxicities of the combination therapy. Treatment related adverse events (as per CTCAE v5.0) will be summarized by grade using frequencies and

Full Information

First Posted
September 27, 2019
Last Updated
August 9, 2023
Sponsor
Roswell Park Cancer Institute
Collaborators
National Comprehensive Cancer Network
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1. Study Identification

Unique Protocol Identification Number
NCT04109924
Brief Title
TAS-102, Irinotecan, and Bevacizumab for the Treatment of Pre-treated Metastatic or Unresectable Colorectal Cancer, the TABAsCO Study
Official Title
A Phase II Study of TAS-102, Irinotecan and Bevacizumab in Pre-Treated Metastatic Colorectal Cancer (TABAsCO)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 27, 2019 (Actual)
Primary Completion Date
July 27, 2023 (Actual)
Study Completion Date
July 17, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
National Comprehensive Cancer Network

4. Oversight

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.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well TAS-102, irinotecan, and bevacizumab work in treating patients with pre-treated colorectal cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Drugs used in chemotherapy, such as TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with bevacizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving TAS-102, irinotecan, and bevacizumab may work better in treating patients with colorectal cancer compared to traditional chemotherapy and bevacizumab.
Detailed Description
PRIMARY OBJECTIVE: I. Determine the median progression free survival (PFS) benefit of leucovorin calcium, 5-fluorouracil, and irinotecan (FOLFIRI) naive patients treated with trifluridine and tipiracil hydrochloride (TAS-102) + irinotecan + bevacizumab as compared to historic control groups treated with FOLFIRI + bevacizumab. SECONDARY OBJECTIVE: I. Estimate the objective response rate (ORR), median overall survival (OS), and adverse event (AE) profile. OUTLINE: Patients receive irinotecan intravenously (IV) over 90 minutes and bevacizumab IV over 30-90 minutes on days 1 and 15. Patients also receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 2-6 and 16-20. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Colorectal Carcinoma, Metastatic Colon Adenocarcinoma, Metastatic Rectal Adenocarcinoma, Recurrent Colon Adenocarcinoma, Recurrent Colorectal Adenocarcinoma, Recurrent Rectal Adenocarcinoma, Stage III Colon Cancer AJCC v8, Stage III Colorectal Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Stage IIIA Colon Cancer AJCC v8, Stage IIIA Colorectal Cancer AJCC v8, Stage IIIB Colorectal Cancer AJCC v8, Stage IIIB Rectal Cancer AJCC v8, Stage IIIC Colon Cancer AJCC v8, Stage IIIC Colorectal Cancer AJCC v8, Stage IV Colon Cancer AJCC v8, Stage IVA Colorectal Cancer AJCC v8, Stage IVA Rectal Cancer AJCC v8, Stage IVB Colon Cancer AJCC v8, Stage IVB Colorectal Cancer AJCC v8, Stage IVB Rectal Cancer AJCC v8, Stage IVC Colon Cancer AJCC v8, Stage IVC Colorectal Cancer AJCC v8, Stage IVC Rectal Cancer AJCC v8, Unresectable Colon Adenocarcinoma, Unresectable Colorectal Carcinoma, Unresectable Rectal Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (irinotecan, bevacizumab, TAS-102)
Arm Type
Experimental
Arm Description
Patients receive irinotecan IV over 90 minutes and bevacizumab IV over 10 minutes on days 1 and 15. Patients also receive trifluridine and tipiracil hydrochloride PO BID on days 2-6 and 16-20. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
(+)-(4S)-4, 11-diethyl-4-hydroxy-9-[(4-piperidino-piperidino)carbonyloxy]-1H-pyrano[3'',4'':6,7]indolizino[1,2-b]quinol-3,14,(4H,12H)-dione, (+)-7-ethyl-10-hydroxycamptothecine 10-[1,4''-bipiperidine]-1''-carboxylate,, 616348,, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin, 728073, 97682-44-5
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
216974-75-3, 704865, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain,, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Trifluridine and Tipiracil Hydrochloride
Other Intervention Name(s)
733030-01-8, Lonsurf, TAS 102, TAS-102, Thymidine, Alpha, Mixt. with 5-Chloro-6-((2-imino-1-pyrrolidinyl)methyl)-2,4(1H,3H)-pyrimidinedione Monohydrochloride, Tipiracil Hydrochloride Mixture with Trifluridine, Trifluridine/Tipiracil,
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Median progression free survival (PFS)
Description
Will be assessed via the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 guidelines. The PFS will be summarized using standard Kaplan-Meier methods, where estimates of the median PFS and 6/12-month PFS rates will be obtained with 90% confidence intervals.
Time Frame
From treatment until disease progression, death due to disease, or last follow-up, assessed up to 2 years post-treatment
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
ill be tabulated based upon RECIST v1.1 criteria. Will be summarized using frequencies and relative frequencies. Using Jeffrey's prior method, a 90% confidence interval about the true ORR will be obtained for each treatment group.
Time Frame
Up to 2 years post-treatment
Title
Median overall survival (OS)
Description
OS will be summarized using standard Kaplan-Meier methods; where estimates of the median survival and 12-month rates are obtained with 90% confidence intervals
Time Frame
From the date of enrollment to the time of death, assessed up to 2 years post-treatment
Title
Disease-specific survival (DSS)
Description
DSS will be summarized using standard Kaplan-Meier methods; where estimates of the median survival and 12-month rates are obtained with 90% confidence intervals.
Time Frame
From treatment until death due to disease or last follow-up, assessed up to 2 years post-treatment
Title
Aggregate rates of adverse events
Description
easured by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and recorded to objectively measure toxicities of the combination therapy. Treatment related adverse events (as per CTCAE v5.0) will be summarized by grade using frequencies and
Time Frame
Up to 30 days after last dose of study drug

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Advanced colorectal cancer (metastatic or unresectable): Histologically or cytological proven adenocarcinoma of the colon or rectum which is metastatic or otherwise incurable Prior treatment with a fluoropyrimidine (5-fluorouracil [5-FU] or capecitabine) and oxaliplatin in the metastatic/unresectable setting OR, recurrence within 12 months of adjuvant therapy with a regimen that included oxaliplatin Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Hemoglobin >= 9 g/dL Absolute neutrophil count >= 1500/mm^3 Platelet count >= 100,000/mm^3 Creatinine < 1.5 upper limit of normal (ULN) or if >= 1.5 x ULN creatinine clearance (CRCL) >= 30 mL/min (by Cockcroft-Gault) Bilirubin < 1.5 x ULN Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN or =< 5 x ULN if with hepatic metastases Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Prior treatment with TAS-102 or irinotecan Anti-cancer therapy within 2 weeks of the planned first dose of study medication Unresolved toxicities from prior therapy of > grade 1, excluding alopecia or similar toxicities which are not deemed to be clinically significant or put the participant at greater risk. Grade 2 neuropathy is permitted Major surgery within 4 weeks of anticipated start of therapy Uncontrolled hypertension: systolic blood pressure >= 150, diastolic blood pressure >= 100 Unstable angina, symptomatic congestive heart failure or cardiac arrhythmia requiring anti-arrhythmic therapy (beta-blockers, calcium channel blockers and digoxin are allowed) Arterial or venous thrombotic or embolic events within 3 months of study initiation, unless well controlled on stable anti-coagulation for >= 2 weeks. This excludes uncomplicated catheter associated venous thrombosis History of cerebrovascular or myocardial ischemia within 6 months of initiation National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 grade 3 or greater hemorrhage within the past 4 weeks Proteinuria >= 2+, unless 24 hour urine collection demonstrates =< 1 g of protein OR spot protein: creatinine demonstrates a ratio of =< 1 Untreated brain metastases History of abnormal glucuronidation of bilirubin (Gilbert's syndrome) History of second primary malignancy within 3 years prior to enrollment, excluding in-situ cervical carcinoma, non-melanoma skin cancer or malignancy of equivalent risk which is highly unlikely to require systemic treatment in the next 2 years Have known active infection which would heighten the risk of complications Pregnant or nursing female participants Unwilling or unable to follow protocol requirements Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christos Fountzilas, MD
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

TAS-102, Irinotecan, and Bevacizumab for the Treatment of Pre-treated Metastatic or Unresectable Colorectal Cancer, the TABAsCO Study

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