Phase III Study in First-line Treatment of Patients With Metastatic Colorectal Cancer Who Are Not Candidate for Intensive Therapy. (SOLSTICE)

• ClinicalTrials.gov Identifier: NCT03869892
• Recruitment Status: Completed
• First Posted: March 11, 2019
• Last Update Posted: April 10, 2023
• Sponsor: Institut de Recherches Internationales Servier
• Collaborator: ADIR, a Servier Group company
• Information provided by (Responsible Party): Servier ( Institut de Recherches Internationales Servier )

Tracking Information

• First Submitted Date: February 23, 2018
• First Posted Date: March 11, 2019
• Last Update Posted Date: April 10, 2023
• Actual Study Start Date: March 21, 2019
• Actual Primary Completion Date: June 29, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 8, 2019)

Progression-free Survival (PFS) [ Time Frame: Up to 24 months ]

Time elapsed between the randomization and the date of radiological tumour progression (according to RECIST 1.1) or death from any cause.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 8, 2019)

• Overall Survival (OS) [ Time Frame: Up to 24 months ]
  Time elapsed between the date of randomization and the date of death due to any cause.
• Overall response rate (ORR) [ Time Frame: Up to 24 months ]
  The proportion of patients with objective evidence of complete response (CR) or partial response (PR) according to RECIST 1.1 criteria and using investigator's tumour assessment.
• Disease control rate (DCR) [ Time Frame: Up to 24 months ]
  The proportion of patients with objective evidence of CR or PR or stable disease (SD) according to RECIST 1.1 criteria and using investigator's tumour assessment.
• Duration of response (DoR) [ Time Frame: Up to 24 months ]
  The time from the first documentation of response (CR or PR) to the first documentation of objective tumour progression or death due to any cause, whichever occurs first.
• Time to treatment failure (TTF) [ Time Frame: Up to 24 months ]
  The time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III Study in First-line Treatment of Patients With Metastatic Colorectal Cancer Who Are Not Candidate for Intensive Therapy.
• Official Title: An Open-label, Randomised, Phase III Study cOmparing trifLuridine/Tipiracil (S 95005) in Combination With Bevacizumab to Capecitabine in Combination With Bevacizumab in firST-line Treatment of Patients With metastatIC Colorectal Cancer Who Are Not candidatE for Intensive Therapy (SOLSTICE Study)
• Brief Summary: The main purpose of this study is to demonstrate the superiority of S 95005 in combination with bevacizumab over capecitabine in combination with bevacizumab.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Colorectal Cancer

Intervention

• Drug: Trifluridine/tipiracil hydrochloride (S95005)
  Film-coated tablets of S 95005 (35 mg/m²/dose) will be administered orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest; This treatment cycle will be repeated every 4 weeks.
• Drug: Capecitabine
  Film-coated tablets, Capecitabine (1250 mg/m²/dose) will be administered orally BID on Days 1-14 of each cycle. This treatment cycle will be repeated every 3 weeks.
• Biological: Bevacizumab experimental
  Concentrate for solution for infusion, Bevacizumab (5 mg/kg, IV) administered every 2 weeks (Day 1 and Day 15). This treatment cycle will be repeated every 4 weeks.
• Biological: Bevacizumab control
  Concentrate for solution for infusion, Bevacizumab (7.5 mg/kg, IV) will be administered on Day 1 of each cycle.This treatment cycle will be repeated every 3 weeks.

Study Arms

• Experimental: S95005 + Bevacizumab
  Interventions:

  • Drug: Trifluridine/tipiracil hydrochloride (S95005)
  • Biological: Bevacizumab experimental
• Active Comparator: Capecitabine + Bevacizumab
  Interventions:

  • Drug: Capecitabine
  • Biological: Bevacizumab control

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 2, 2022): 874
• Original Estimated Enrollment (submitted: March 8, 2019): 854
• Actual Study Completion Date: October 1, 2022
• Actual Primary Completion Date: June 29, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Has definitive histologically confirmed adenocarcinoma of the colon or rectum (all other histological types are excluded). Primary tumour localisation must be known.
2. RAS status based on local biological assessment of tumour biopsy must be available. If RAS status is not available at the time of randomisation, tumour biopsy must be available for RAS status determination (based on local biological assessment).
3. Patient is not a candidate for standard full dose combination chemotherapy with irinotecan or oxaliplatin
4. Patient is not a candidate for curative resection of metastatic lesions.
5. No previous systemic anticancer therapy for unresectable metastatic colorectal cancer.
6. ECOG (Eastern Cooperative Oncology Group) performance status ≤2.

7. Adequate organ function (renal, haematological, hepatic, coagulation) as described in the study protocol'

   Exclusion Criteria:

8. Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
9. Participation in another interventional study within 4 weeks prior to the randomisation .
10. Patients who have not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to the randomisation.
11. Symptomatic central nervous system metastases.

12. Major surgery within 4 weeks prior to the randomisation.

    Exclusion criteria related to S 95005 administration:

13. History of allergic reactions attributed to compounds of similar composition to S 95005 or any of its excipients.

14. Any contraindication present in the SmPC of trifluridine/tipiracil

    Exclusion criteria related to bevacizumab administration:

15. Any contraindication present in the SmPC of bevacizumab

    Exclusion criteria related to capecitabine administration:

16. Any contraindication present in the SmPC of capecitabine

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Brazil, Bulgaria, Czechia, Denmark, Estonia, France, Germany, Hungary, Ireland, Italy, Latvia, Lithuania, Netherlands, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Sweden, Ukraine, United Kingdom

Administrative Information

• NCT Number: NCT03869892
• Other Study ID Numbers: CL3-95005-006; 2017-004059-22 ( EudraCT Number ); U1111-1206-3198 ( Other Identifier: UTN )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• 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: https://clinicaltrials.servier.com/

• Current Responsible Party: Servier ( Institut de Recherches Internationales Servier )
• Original Responsible Party: Same as current
• Current Study Sponsor: Institut de Recherches Internationales Servier
• Original Study Sponsor: Same as current
• Collaborators: ADIR, a Servier Group company

Investigators

• Principal Investigator: Thierry ANDRE, PhD; Medical Oncology departement Saint-Antoine hospital (Paris France 75012)

• PRS Account: Servier
• Verification Date: April 2023