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

NCT ID: NCT04109924

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-27
• Study Completion Date: 2024-09-05

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (irinotecan, bevacizumab, TAS-102)

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.

Group Type: EXPERIMENTAL

Irinotecan

Intervention Type: DRUG

Given IV

Bevacizumab

Intervention Type: BIOLOGICAL

Given IV

Trifluridine and Tipiracil Hydrochloride

Intervention Type: DRUG

Given PO

Interventions

Irinotecan

Given IV

Intervention Type: DRUG

Bevacizumab

Given IV

Intervention Type: BIOLOGICAL

Trifluridine and Tipiracil Hydrochloride

Given PO

Intervention Type: DRUG

Other Intervention Names

(+)-(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; 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; 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,

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Comprehensive Cancer Network

NETWORK

Sponsor Role: collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christos Fountzilas, MD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Moffitt Cancer Center

Tampa, Florida, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Countries

United States

References

Boland PM, Mukherjee S, Imanirad I, Vijayvergia N, Cohen SD, Gupta M, Iyer RV, Bakin A, Wang J, Chatley S, Cahill B, Vadehra D, Attwood K, Hochster HS, Fountzilas C. TAS-102, Irinotecan, and bevacizumab in pre-treated metastatic colorectal cancer (TABAsCO), a phase II clinical trial. Br J Cancer. 2024 Nov;131(8):1290-1297. doi: 10.1038/s41416-024-02845-x. Epub 2024 Sep 7.

Reference Type: DERIVED

PMID: 39244627 (View on PubMed)

Other Identifiers

I 444019

Identifier Type: -

Identifier Source: org_study_id