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
- Conditions
- metastatic colorectal cancer10017991
- Registration Number
- NL-OMON52901
- Lead Sponsor
- Servier R&D Benelux
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 35
- Written informed consent obtained
- 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. 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.
- 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 excluding malignancies that are in remission for more than
5 years, cervix carcinoma-in-situ deemed cured by adequate treatment or basal
cell carcinoma.
- 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Progression-free survival (PFS) based on Investigator assessment .</p><br>
- Secondary Outcome Measures
Name Time Method <p>Key secondary endpoint: Overall survival (OS)<br /><br>Other secondary endpoints :<br /><br>Overall response rate (ORR)<br /><br>Disease control rate (DCR)<br /><br>Duration of response (DoR)<br /><br>Time to treatment failure (TTF)<br /><br>Safety and tolerability<br /><br>Quality of life (Qol) (EORTC QLQ-C30 and EQ-5D-5L)</p><br>