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

NCT04109924 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: I 444019
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 4

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Medical record review will be performed approximately every 6 months, for up to 2 years, post treatment up to 4 years

Secondary Outcomes (4)

• Number of Participants With Complete Response, Partial Response, Stable Disease and Progressive Disease

  Medical record review will be performed approximately every 6 months, for up to 2 years, post treatment up to 4 years

• Median Overall Survival (OS)

  Medical record review will be performed approximately every 6 months, for up to 2 years, post treatment up to 4 years

• Disease-specific Survival (DSS)

  Medical record review will be performed approximately every 6 months, for up to 2 years, post treatment up to 4 years

• Aggregate Rates of Adverse Events

  Follow-up safety evaluations will occur 30 days (± 3 days) after last dose of study drug or until resolution of any drug related toxicity (telephone contact is acceptable), through study completion , an average of 3.5 years work

Study Arms (1)

Treatment (irinotecan, bevacizumab, TAS-102)

EXPERIMENTAL

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.

Drug: Irinotecan; Biological: Bevacizumab; Drug: Trifluridine and Tipiracil Hydrochloride

Interventions

Irinotecan DRUG

Given IV

Also known as: (+)-(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

Treatment (irinotecan, bevacizumab, TAS-102)

Bevacizumab BIOLOGICAL

Given IV

Also known as: 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

Treatment (irinotecan, bevacizumab, TAS-102)

Trifluridine and Tipiracil Hydrochloride DRUG

Given PO

Also known as: 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,

Treatment (irinotecan, bevacizumab, TAS-102)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (4)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (1)

• 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.

  PMID: 39244627 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Colorectal Neoplasms

Interventions

Irinotecan; Bevacizumab; Disulfides; Trifluridine; trifluridine tipiracil drug combination; Thymidine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Benczkowski, Kimberly， CTRP/CT.gov Registry Coordinator
• Organization: Roswell Park Cancer institute

Kimberly.Benczkowski@RoswellPark.org

716 8451300

Study Officials

• Christos Fountzilas, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: October 1, 2019
• Study Start: December 27, 2019
• Primary Completion: September 5, 2024
• Study Completion: September 5, 2024
• Last Updated: February 10, 2026
• Results First Posted: February 10, 2026

Record last verified: 2025-11

Locations

US (4)