Study of Efficacy and Safety of S 95005 (TAS-102) in Patients With Metastatic Colorectal Cancer Who Failed Standard Chemotherapies

Open-label Multicentre Confirmatory Study of Efficacy and Safety of S 95005 (TAS-102) in Patients With Metastatic Colorectal Cancer Who Are Refractory or Intolerant to Standard Chemotherapies

The purpose of this study is to evaluate the efficacy of S 95005 in patients with metastatic colorectal cancer (mCRC) who are refractory or intolerant to standard chemotherapies in terms of Progression-Free Survival rate at 2 months in the Russian population.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: S95005

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Russian Cancer Research Center n.a. NN Blokhin (RCRC), Clinical Pharmacology and Chemotherapy department
  • Saint Petersburg, Russian Federation, 197758
    • Saint Petersburg Clinical Scientific-Practical Center of Special Medical Care (Oncology Center)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female aged ≥18 years of age
• Has definitive histologically or cytologically confirmed adenocarcinoma of the colon or rectum
• Has received at least 2 prior regimens of standard chemotherapies for metastatic colorectal cancer (including fluoropyrimidines, irinotecan and oxaliplatin and, if accessible, an anti-VEGF monoclonal antibody and at least one of the anti-EGFR monoclonal antibodies for RAS wild-type patients (if RAS mutation status was evaluated)) and was refractory or intolerant to those chemotherapies
• Has Eastern Cooperative Group (ECOG) performance status of 0 or 1
• Has at least one measurable metastatic lesion(s)
• Has adequate organ function
• Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control during the study and for 6 months after the discontinuation of study medication

Exclusion Criteria:

• Pregnancy, breastfeeding
• Participation in another interventional study within 4 weeks prior to inclusion; participation in non-interventional registries or epidemiological studies is allowed
• Has previously received S95005 or history of allergic reaction attributed to compounds of similar composition to S95005
• Has a serious illness or medical condition(s) as described in the protocol
• Has had certain other recent treatment e.g. major surgery, field radiation, anticancer therapy, within the specified time frames prior to inclusion
• Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 attributed to any prior therapies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: S95005; Film-coated tablet containing 15 mg of trifluridine and 7.065 mg of tipiracil hydrochloride, or 20 mg of trifluridine and 9.42 mg of tipiracil hydrochloride (with a molar ratio of 1:0.5) was administered at 35 mg/m²/dose orally twice a day, 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. This treatment cycle was repeated every 4 weeks until treatment withdrawal criteria are met.

Drug: S95005; The treatment is given in open manner. It was administered until unacceptable toxicity according to the investigator, disease progression or patient withdrawal. If a patient discontinues study treatment for reasons other than radiologic disease progression (e.g., intolerable side effects), the patient was followed for tumour response until radiologic disease progression or initiation of new anticancer therapy (whichever occurs first).; Other Names: TAS-102

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) rate	percentage of patients alive without investigator-assessed radiological disease progression according to RECIST 1.1 after 2 months	at 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS).	based on Investigator review of the images according to RECIST 1.1	Through study completion, an average of 12 weeks
Overall Response Rate (ORR).	based on Investigator review of the images according to RECIST 1.1	Through study completion, an average of 12 weeks
Disease Control Rate (DCR)	based on Investigator review of the images according to RECIST 1.1	Through study completion, an average of 12 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]		Through study completion, an average of 12 weeks
Abnormalities in laboratory tests (haematology, blood biochemistry and urinalysis) [safety and tolerability]		Through study completion, an average of 12 weeks
Abnormalities in physical examination and performance status (ECOG) [safety and tolerability]		Through study completion, an average of 12 weeks
Abnormalities in blood pressure [safety and tolerability]		Through study completion, an average of 12 weeks
Abnormalities in heart rate [safety and tolerability]		Through study completion, an average of 12 weeks
Abnormalities in body temperature [safety and tolerability]		Through study completion, an average of 12 weeks
Abnormalities in respiration rate [safety and tolerability]		Through study completion, an average of 12 weeks
Abnormalities in body weight [safety and tolerability]		Through study completion, an average of 12 weeks
Abnormalities in 12-leads ECG parameters [safety and tolerability]		Through study completion, an average of 12 weeks

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company
• Investigators: Principal Investigator: Vladimir MOISEENKO, Prof., Saint Petersburg Clinical Scientific-Practical Center of Specialized Medical Care (Oncological)

Publications and helpful links

Helpful Links

• Lay Summary
• Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2017
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 3, 2018

Study Registration Dates

• First Submitted: August 2, 2017
• First Submitted That Met QC Criteria: September 6, 2017
• First Posted (Actual): September 7, 2017

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: cancer; Russia; colorectal; metastatic; Lonsurf; S95005
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: CL2-95005-003; ISRCTN14228310 (Registry Identifier: ISRCTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
2. Study Protocol
3. Statistical Analysis Plan
4. Informed Consent Form
5. Clinical Study Report
6. Study-level clinical trial data

Drug and device information, study documents

• 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.: Yes