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

Sponsor
Roswell Park Cancer Institute (Other)
Overall Status
Recruiting
CT.gov ID
NCT04109924
Collaborator
National Comprehensive Cancer Network (Other)
42
4
1
51.8
10.5
0.2

Study Details

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:
  1. 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:
  1. 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
42 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of TAS-102, Irinotecan and Bevacizumab in Pre-Treated Metastatic Colorectal Cancer (TABAsCO)
Actual Study Start Date :
Dec 27, 2019
Anticipated Primary Completion Date :
Apr 22, 2024
Anticipated Study Completion Date :
Apr 22, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Irinotecan
Given IV
Other 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
  • Biological: Bevacizumab
    Given IV
    Other Names:
  • 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
  • Drug: Trifluridine and Tipiracil Hydrochloride
    Given PO
    Other Names:
  • 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,
  • Outcome Measures

    Primary Outcome Measures

    1. Median progression free survival (PFS) [From treatment until disease progression, death due to disease, or last follow-up, assessed up to 2 years post-treatment]

      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

    1. Objective response rate (ORR) [Up to 2 years post-treatment]

      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.

    2. Median overall survival (OS) [From the date of enrollment to the time of death, assessed up to 2 years post-treatment]

      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

    3. Disease-specific survival (DSS) [From treatment until death due to disease or last follow-up, assessed up to 2 years post-treatment]

      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.

    4. Aggregate rates of adverse events [Up to 30 days after last dose of study drug]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Moffitt Cancer Center Tampa Florida United States 33612
    2 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08903
    3 Roswell Park Cancer Institute Buffalo New York United States 14263
    4 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111

    Sponsors and Collaborators

    • Roswell Park Cancer Institute
    • National Comprehensive Cancer Network

    Investigators

    • Principal Investigator: Christos Fountzilas, MD, Roswell Park Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Roswell Park Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT04109924
    Other Study ID Numbers:
    • I 444019
    First Posted:
    Oct 1, 2019
    Last Update Posted:
    Jun 23, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 23, 2022