Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Evaluating S 95005 Plus Bevacizumab and Capecitabine Plus Bevacizumab in Patients With Previously Untreated Colorectal Cancer Who Are Non-eligible for Intensive Therapy (TASCO1)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02743221
Recruitment Status : Active, not recruiting
First Posted : April 19, 2016
Results First Posted : April 16, 2019
Last Update Posted : October 1, 2019
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

Tracking Information
First Submitted Date  ICMJE February 24, 2016
First Posted Date  ICMJE April 19, 2016
Results First Submitted Date  ICMJE January 15, 2019
Results First Posted Date  ICMJE April 16, 2019
Last Update Posted Date October 1, 2019
Actual Study Start Date  ICMJE April 29, 2016
Actual Primary Completion Date January 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2019)
Progression Free Survival (PFS) [ Time Frame: Baseline and every 8 weeks (maximum follow-up duration: 17.9 months) ]
The progression free survival (PFS), defined as the time from the date of randomisation until the date of the investigator-assessed radiological disease progression or death due to any cause according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive disease (PD) was defined at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and an absolute increase of at least 5 mm in the sum of lesions or the appearance of new lesions.
Original Primary Outcome Measures  ICMJE
 (submitted: April 14, 2016)
Progression Free Survival (PFS) [ Time Frame: Up to 12 months. ]
Change History Complete list of historical versions of study NCT02743221 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2019)
  • Overall Response Rate (ORR) [ Time Frame: Baseline and every 8 weeks (maximum follow-up duration: 17.9 months) ]
    As per RECIST v1.1, Complete Response (CR) was disappearance of all target lesions; Partial Response (PR) was at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ORR was the proportion of patients who presented CR or PR with confirmation at subsequent time point or at least 4 weeks later.
  • Duration of Response (DR) [ Time Frame: Baseline and every 8 weeks (maximum follow-up duration: 16.6 months) ]
    The DR was calculated among patients with CR or PR as the time (months) from the first documentation of response to the first documentation of objective tumor progression or death due to any cause, whichever occurred first.
  • Disease Control Rate (DCR) [ Time Frame: Baseline and every 8 weeks (maximum follow-up duration: 17.9 months) ]
    DCR was the proportion of patients with confirmed CR, PR or stable disease (SD) as best overall response. SD defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD.
  • Overall Survival (OS) [ Time Frame: Baseline up to death or study cut-off (maximum follow-up duration: 19.9 months) ]
    The OS was defined as the time from the date of randomisation to the date of death. If death was not confirmed, or patient was alive at study cut-off date, survival time was censored at the date of last follow-up or at the study cut-off date, whichever was earlier.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2016)
  • Overall Response Rate (ORR) [ Time Frame: Up to 12 months. ]
  • Duration of Response (DR) [ Time Frame: Up to 12 months. ]
  • Disease Control Rate (DCR) [ Time Frame: Up to 12 months. ]
  • Overall Survival (OS) [ Time Frame: Up to 2 years. ]
  • Safety and tolerability assessed by incidence of Adverse Events [ Time Frame: Up to 12 months. ]
  • Safety and tolerability assessed by laboratory tests [ Time Frame: Up to 12 months. ]
  • Safety and tolerability assessed by physical examination [ Time Frame: Up to 12 months. ]
  • Safety and tolerability assessed by performance status (ECOG) [ Time Frame: Up to 12 months. ]
  • Safety and tolerability assessed by vital signs [ Time Frame: Up to 12 months. ]
  • Safety and tolerability assessed by 12-leads ECG parameters [ Time Frame: Up to 12 months. ]
  • Quality of Life assessed by a quality of life questionnaire. [ Time Frame: Up to 12 months. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: April 14, 2016)
  • Circulating protein biomarkers analysis [ Time Frame: through study completion, an average of 12 months ]
    Samples collected at C1D1 (day 1 of cycle 1) and at withdrawal will be subjected to Dproteomic analysis for identification of potential predictive and resistance biomarkers for S 95005 and/or bevacizumab response or biological activity in comparison to capecitabine + bevacizumab arm. Biomarkers in relation to the metabolic pathway of S 95005 and capecitabine will be assessed.
  • Circulating tumour DNA analysis [ Time Frame: day 1 of cycle 1 (each cycle is 28 days) ]
    Samples collected at C1D1 will be subjected to genomic analysis to study mutations currently observed in colorectal cancer
  • Proteomic analysis on archived biopsy [ Time Frame: day 1 of cycle 1 (each cycle is 28 days) ]
    Archived biopsy collected at metastatic stage diagnosis, will be recovered at C1D1 and subjected to proteomic analysis in relation to the metabolic pathway of S 95005 and capecitabine for identification of biomarkers that may predict response to S 95005 and capecitabine in combination with bevacizumab
  • Genomic analysis on archived biopsy [ Time Frame: day 1 of cycle 1 (each cycle is 28 days) ]
    Archived biopsy collected at metastatic stage diagnosis, will be recovered at C1D1 and subjected to microsatellite instability analysis for identification of biomarkers that may predict response to S 95005 and capecitabine in combination with bevacizumab
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating S 95005 Plus Bevacizumab and Capecitabine Plus Bevacizumab in Patients With Previously Untreated Colorectal Cancer Who Are Non-eligible for Intensive Therapy
Official Title  ICMJE An Open-label, Randomised, Non-comparative Phase 2 Study Evaluating S 95005 (TAS-102) Plus Bevacizumab and Capecitabine Plus Bevacizumab in Patients With Previously Untreated Metastatic COlorectal Cancer Who Are Non-eligible for Intensive Therapy (TASCO1 Study).
Brief Summary The main purpose of this study is to evaluate the progression-free survival (PFS) in patients receiving S 95005 + bevacizumab (experimental arm) or capecitabine + bevacizumab (control arm) as first-line treatment for unresectable metastatic colorectal cancer in patients non-eligible for intensive therapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Colorectal Cancer
Intervention  ICMJE
  • Drug: Trifluridine/tipiracil + bevacizumab
    Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.
  • Drug: Capecitabine + bevacizumab
    Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.
Study Arms  ICMJE
  • Experimental: Trifluridine/tipiracil + bevacizumab

    Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride.

    Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab.

    Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks.

    Intervention: Drug: Trifluridine/tipiracil + bevacizumab
  • Active Comparator: Capecitabine + bevacizumab
    Capecitabine was administered at 1250 mg/m² orally BID (bis in die)on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks
    Intervention: Drug: Capecitabine + bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 25, 2019)
154
Original Estimated Enrollment  ICMJE
 (submitted: April 14, 2016)
150
Estimated Study Completion Date  ICMJE April 22, 2020
Actual Primary Completion Date January 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent obtained.
  • Has ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1 or 2 at the time of the randomisation.
  • Has definitive histologically or cytologically confirmed adenocarcinoma of the colon or rectum.
  • RAS status must have been determined (mutant or wild).
  • Has at least one measurable metastatic lesion.
  • No previous systemic anticancer therapy for unresectable metastatic colorectal cancer.
  • Previous adjuvant (or neoadjuvant for patients with rectal cancer) chemotherapy is allowed only if if it has been completed more than 6 months before start of study treatment.
  • Patient is not a candidate for combination chemotherapy with irinotecan or oxaliplatin, or for curative resection of metastatic lesions.
  • Is able to take medication orally (i.e., no feeding tube).
  • Has adequate organ function.
  • Coagulation parameters in normal limit (or in therapeutic limit for patients treated with anticoagulant drugs).
  • Women of childbearing potential must have been tested negative in a serum pregnancy test. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control. Women and female partners using hormonal contraceptive must also use a barrier method.

Exclusion Criteria:

  • Is a pregnant or lactating female.
  • Has certain serious illness or serious medical condition(s) as described in the protocol.
  • Has had certain other recent treatment e.g. major surgery, field radiation, received investigational agent, within the specified time frames prior to randomisation.
  • Has previously received Trifluridine/tipiracil or history of allergic reactions attributed to compounds of similar composition to Trifluridine/tipiracil or any of its excipients.
  • Has rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
  • Has contra-indication to bevacizumab or capecitabine.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Brazil,   Denmark,   France,   Germany,   Italy,   Netherlands,   Poland,   Russian Federation,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02743221
Other Study ID Numbers  ICMJE CL2-95005-002
2015-004544-18 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask all interventional clinical studies:

  • submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
URL: http://clinicaltrials.servier.com
Responsible Party Servier ( Institut de Recherches Internationales Servier )
Study Sponsor  ICMJE Institut de Recherches Internationales Servier
Collaborators  ICMJE ADIR, a Servier Group company
Investigators  ICMJE
Principal Investigator: Eric Van Custem, Prof Leuven Cancer Institute, University Hospitals Leuven
PRS Account Servier
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP