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

• ClinicalTrials.gov Identifier: NCT03274882
• Recruitment Status: Completed
• First Posted: September 7, 2017
• Last Update Posted: May 11, 2023
• Sponsor: Institut de Recherches Internationales Servier
• Collaborator: ADIR, a Servier Group company
• Information provided by (Responsible Party): Servier ( Institut de Recherches Internationales Servier )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Colorectal Cancer	Drug: S95005	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: March 3, 2017
• Actual Primary Completion Date: December 31, 2017
• Actual Study Completion Date: December 3, 2018

Arms and Interventions

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 Name: TAS-102

Outcome Measures

Primary Outcome Measures :

1. Progression free survival (PFS) rate [ Time Frame: at 2 months ]
   percentage of patients alive without investigator-assessed radiological disease progression according to RECIST 1.1 after 2 months

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Russian Federation

Russian Cancer Research Center n.a. NN Blokhin (RCRC), Clinical Pharmacology and Chemotherapy department

Moscow, Russian Federation, 115478

Saint Petersburg Clinical Scientific-Practical Center of Special Medical Care (Oncology Center)

Saint Petersburg, Russian Federation, 197758

Sponsors and Collaborators

Institut de Recherches Internationales Servier

ADIR, a Servier Group company

Investigators

• Principal Investigator: Vladimir MOISEENKO, Prof.; Saint Petersburg Clinical Scientific-Practical Center of Specialized Medical Care (Oncological)

More Information

Additional Information:

Lay Summary 

Results Summary 

Study Data/Documents: Individual Participant Data Set 

Study Protocol 

Statistical Analysis Plan 

Informed Consent Form 

Clinical Study Report 

Study-level clinical trial data 

• Responsible Party: Institut de Recherches Internationales Servier
• ClinicalTrials.gov Identifier: NCT03274882
• Other Study ID Numbers: CL2-95005-003; ISRCTN14228310 ( Registry Identifier: ISRCTN )
• First Posted: September 7, 2017
• Last Update Posted: May 11, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• 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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); 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

• 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

Keywords provided by Servier ( Institut de Recherches Internationales Servier ):

metastatic; colorectal; cancer; Lonsurf; S95005; Russia

Additional relevant 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