Phase III study in first-line treatment of patients with metastatic colorectal cancer who are not candidate for intensive therapy

Phase 1

• Conditions: Metastatic colorectal cancer; MedDRA version: 21.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004059-22-DE
• Lead Sponsor: Institut de Recherches Internationales Servier

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-14
• Last Update Posted: 1 February 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 854

Inclusion Criteria

- Male or female participant aged =18 years old at the time of ICF signature (or legal age depending on local country regulation).
- 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.
- 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 multidisciplinary 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, including systemic use of chemotherapy agents as radiosensitizers. 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, 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 potential and male participants with partner of childbearing potential must use an highly effective method of birth control as well as their partners lasting at least 6 months after the last dose of IMP. Women using hormonal contraceptive must also use a barrier method.
- Written informed consent obtained.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 213
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 641

Exclusion Criteria

- Unlikely to cooperate in the study.
- Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
- Participation in another interventional study, 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 including those which were radically treated and for which the remission period at the time of screening is less than five years. Exemptions for a minimally required duration of remission period may be applied for carcinoma in situ of the cervix and basal cell skin cancer that are deemed to be cured by adequate treatment.
- Treatment with systemic immunosuppressive therapy (except steroids given in prophylactic setting or at a chronic low dose (=20mg/day prednisone equivalent)).
- Criteria related to S 95005 administration:
Has previously received S 95005.
History of allergic reactions attributed to compounds of similar composition to S 95005 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified