Informationen für den behandelnden Arzt
Sponsorvertreter der Studie in Deutschland:
SERVIER Forschung Pharma-Entwicklung GmbH
(Sponsor in Frankreich: Institut de Recherches Internationales Servier in Paris)
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)
Principal inclusion criteria:
- Male or female participant aged ≥ 18 years old at the time of ICF signature (or legal age depending on local country regulation).
Medical and therapeutic criteria
- Has definitive histologically confirmed adenocarcinoma of the colon or rectum
- Has at least one measurable metastatic lesion 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).
- Patient is not a candidate for standard full dose combination chemotherapy with irinotecan or oxaliplatin according to investigator’s judgment and decision taken during a multi-disciplinary meeting (if organised in the centre).
- Reasons for non-eligibility to these standard treatments could be, but are not limited to, age, performance status, low tumour burden, comorbidities or non-clinical reasons.
- Patient is not a candidate for curative resection of metastatic lesions according to investigator’s judgment and decision taken during a multidisciplinary meeting (if organised in the centre).
- No previous systemic anticancer therapy for unresectable metastatic colorectal cancer. Previous adjuvant or neoadjuvant chemotherapy is allowed only if the patient has been disease free for at least 6 months after the completion of the chemotherapy.
- Ability to swallow oral medication.
- Estimated life expectancy ≥ 12 weeks.
- ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2. Adequate haematological, renal (creatinine clearance ≥ 50 ml/min) hepatic, and coagulation function
- Women of childbearing potential must have been tested negative in a serum pregnancy test
- Within the frame of this study, female participants of childbearing and male participants with partners of childbearing potential must use a highly effective method of birth control, as well as their partners lasting at least 6 months after the last dose of IMP
Principal exclusion criteria:
- Unlikely to cooperate in the study.
- Pregnancy, breastfeeding or possibility of becoming pregnant during the study
- Participation in another interventional study within 4 weeks prior to the randomisation (participation in follow-up part without IMP administration is allowed). Participation in non-interventional registries or epidemiological studies is allowed.
Medical and therapeutic criteria
- Major surgery, drainage for ascites, pleural effusion or pericardial fluid, previous radiotherapy, within the specified timeframes prior to the randomisation.
- Patients who have not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to the randomisation.
- Symptomatic central nervous system metastases. Has certain serious illness or serious medical condition(s) described in the protocol.
- Hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
- Other malignancies excluding malignancies that are in remission for more than 5 years, cervix carcinoma-in-situ deemed cured by adequate treatment or basal cell carcinoma.
Criteria related to Trifluridin+Tipiracil administration:
- Has previously received Trifluridin+Tipiracil.
- History of allergic reactions attributed to compounds of similar composition to Trifluridin+Tipiracil or any of its excipients.
- Any contraindication present in the SmPC of trifluridine/tipiracil
Criteria related to bevacizumab administration:
- History of allergic reactions or hypersensitivity to bevacizumab or any of its excipients.
- History of hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies. Serious non-healing wound, non-healing ulcer or non-healing bone fracture.
- Deep venous thromboembolic event within 4 weeks prior to randomisation,
Known coagulopathy that increases risk of bleeding, bleeding diatheses. Any other
haemorrhage/bleeding event CTCAE grade ≥ 3 within 4 weeks prior to randomisation.
- Any contraindication present in the SmPC of bevacizumab
Criteria related to capecitabine administration:
- History of allergic reactions or hypersensitivity to capecitabine or any of its excipients or fluorouracil.
- History of severe and unexpected reaction to fluoropyrimidine therapy.
- Known complete absence of dihydropyrimidine dehydrogenase (DPD) activity or partial deficiency of DPD preventing the administration of the starting dose of capecitabine as defined per study protocol.
- Treatment with sorivudine or its chemical related analogues, such as brivudine, within 4 weeks prior to the randomisation.
- Any contraindication present in the SmPC of capecitabine.
Link zur Studie in der EudraCT Datenbank:
Link zur Studie auf der SERVIER Interneitseite:
Verweise auf Publikationen:
Vorherige Studie mit Trifluridin+Tipiracil:
Cunningham D., et al. "Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial." Lancet Oncology, 2013: 1077-85
Pinto C., et al. "Efficacy and safety of bevacizumab combined with fluoropyrimidine monotherapy for unfit or older patients with metastatic colorectal cancer: a systemic review and meta-analysis." Clinical Colorectal Cancer, 2016: 61-72.