We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trifluridine/Tipiracil in Combination With Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients. (TriComB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04564898
Recruitment Status : Recruiting
First Posted : September 25, 2020
Last Update Posted : February 3, 2022
Sponsor:
Information provided by (Responsible Party):
Gruppo Oncologico del Nord-Ovest

Brief Summary:
The aim oh this study is to determine the safety and recommended dose of trifluridine/tipiracil plus capecitabine and bevacizumab combination (part 1, dose escalation phase) and to assess its activity in previously untreated mCRC patients who are deemed not eligible for intensive chemotherapy (part 2, expansion phase).

Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastatic Drug: Capecitabine Drug: Bevacizumab Drug: Trifluridine/Tipiracil Phase 1 Phase 2

Detailed Description:

This is an open-label, multicenter, phase 1/2 study evaluating the safety and activity of trifluridine/tipiracil in combination with capecitabine and bevacizumab in mCRC. The first part (Part 1) of the study will consist in a dose-escalation assessment of the safety of the treatment in subjects with previously untreated mCRC deemed not fit for irinotecan- and/or oxaliplatin- based regimens (i. e. FOLFOX/XELOX/FOLFIRI/FOLFOXIRI with or without targeted agents).

The second part (Part 2) will be an open-label phase 2 study with a Fleming's single-stage design to evaluate the ORR of the study treatment at the recommended dose established in the first part of the study in the same patients' population.

Trifluridine/tipiracil, capecitabine and bevacizumab will be administered in 28-days cycles until progressive disease, unacceptable toxicities, or patients' refusal.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study Exploring the Safety and Activity of Trifluridine/Tipiracil in Combination With Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients
Actual Study Start Date : January 25, 2022
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: trifluridine/tipiracil plus capecitabine and bevacizumab Drug: Capecitabine

Part 1 • Capecitabine, 1000 mg/sqm orally twice daily on days 1-14 each 28 days

Part 2

• Capecitabine, 1000 mg/sqm orally twice daily on days 1-14 each 28 days


Drug: Bevacizumab

Part 1 • Bevacizumab, 5 mg/kg IV dose over 30 minutes on days 1 and 15 each 28 days

Part 2

• Bevacizumab, 5 mg/kg IV dose over 30 minutes on days 1 and 15 each 28 days


Drug: Trifluridine/Tipiracil

Part 1 • Trifluridine/tipiracil, dose escalation from 25 mg/sqm to 35 mg/sqm orally twice daily on days 15-19 (and days 22-26) each 28 days

Part 2

• Trifluridine/tipiracil, at the recommanded dose established during part 1 orally twice daily on days 15-19 (and days 22-26) each 28 days





Primary Outcome Measures :
  1. recommended dose [ Time Frame: 2 years ]
    recommended dose of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab

  2. activity [ Time Frame: 3 years ]
    activity of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab in terms of overaal response rate per RECIST v1.1.


Secondary Outcome Measures :
  1. quality of life for cancer patients [ Time Frame: 3 years ]
    quality of life as measured by EORTC QLQ-C30 questionnaire.

  2. quality of life for colorectal cancer patients [ Time Frame: 3 years ]
    quality of life as measured by EORTC QLQ-CR29 questionnaire.

  3. quality of life for dimensions health [ Time Frame: 3 years ]
    quality of life as measured by EuroQol EQ-5D questionnaire.

  4. survival [ Time Frame: 3 years ]
    efficacy of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab in terms of progression-free survival and overall survival


Other Outcome Measures:
  1. bioavailability [ Time Frame: 2 years ]
    Absolute and relative bioavailability of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.

  2. Steady state concentration [ Time Frame: 2 years ]
    Steady state concentration of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.

  3. Therapeutic index [ Time Frame: 2 years ]
    Therapeutic index of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.

  4. Volume of distribution [ Time Frame: 2 years ]
    Volume of distribution of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.

  5. Half-life [ Time Frame: 2 years ]
    Plasma half-life of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.

  6. Clearance [ Time Frame: 2 years ]
    Clearance of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent to study procedures.
  • Histologically proven diagnosis of colorectal cancer.
  • Metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
  • At least one measurable lesion according to RECIST1.1.
  • Age ≥ 18 years.
  • ECOG PS ≤ 1.
  • Life expectancy of at least 12 weeks.
  • Previous adjuvant fluoropyrimidine-based chemotherapy allowed only if more than 12 months elapsed between the end of adjuvant and first relapse.
  • Availability of archival tumour tissue (primary tumour and metastases or at least one of the two) for biomarker analysis.
  • Availability of blood sample for biomarker analysis.
  • Previously not eligible for a chemotherapy doublet or triplet (oxaliplatin and/or irinotecan-based combination).
  • Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hemoglobin ≥ 9 g/dl.
  • Total bilirubin ≤1.5 fold the upper-normal limits (UNL), AST (SGOT) and/or ALT (SGPT) ≤ 2.5 x UNL (or <5 x UNL in the case of liver metastases), alkaline phosphatase ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases).
  • Creatinine clearance ≥ 50 mL/min or serum creatinine ≤1.5 x UNL.
  • Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception).
  • Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.
  • Subjects and their partners must be willing to avoid pregnancy during the trial and until 6 months after the last trial treatment.
  • Will and ability to comply with the protocol.

Exclusion Criteria:

  • Radiotherapy to any site within 4 weeks before the study.
  • Previous treatment with trifluridine/tipiracil, bevacizumab and capecitabine (previous treatment with capecitabine was permitted only in the adjuvant setting and if more than 12 months elapsed between the end of adjuvant and first relapse).
  • Untreated brain metastases or spinal cord compression or primary brain tumors.
  • History or evidence upon physical examination of CNS disease unless adequately treated.
  • Clinical signs of malnutrition.
  • Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration.
  • Evidence of bleeding diathesis or coagulopathy.
  • Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
  • Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
  • Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment.
  • Any previous venous thromboembolism ≥ NCI CTCAE Grade 4.
  • History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment.
  • Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer).
  • Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ.
  • Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
  • Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.
  • Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.
  • Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04564898


Contacts
Layout table for location contacts
Contact: Chiara Cremolini, MD, PhD +39.050.992192 chiaracremolini@gmail.com
Contact: Laura Delliponti, MD +39.050.992192 tricombstudy@gmail.com

Locations
Layout table for location information
Italy
Fondazione IRCCS Istituto Nazionale Tumori Not yet recruiting
Milano, MI, Italy, 20133
Contact: Filippo Pietrantonio, MD       Filippo.Pietrantonio@istitutotumori.mi.it   
Principal Investigator: Filippo Pietrantonio         
Azienda Ospedaliero Universitaria Pisana Recruiting
Pisa, PI, Italy, 56126
Contact: Gianluca Masi, MD    +39050992466    gianluca.masi@unipi.it   
Contact: Chiara Cremolini, MD    +39050992192    chiaracremolini@gmail.com   
Principal Investigator: Gianluca Masi, MD         
Sub-Investigator: Chiara Cremolini, MD         
Sponsors and Collaborators
Gruppo Oncologico del Nord-Ovest
Investigators
Layout table for investigator information
Study Chair: Chiara Cremolini, MD, PhD Fondazione GONO
Layout table for additonal information
Responsible Party: Gruppo Oncologico del Nord-Ovest
ClinicalTrials.gov Identifier: NCT04564898    
Other Study ID Numbers: EUDRACT 2020-000923-37
First Posted: September 25, 2020    Key Record Dates
Last Update Posted: February 3, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Trifluridine
Bevacizumab
Capecitabine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents