Phase I dose-escalation study of S 81694 administered intravenously in adult patients with advanced/metastatic solid tumours
- Conditions
- Advanced/metastatic Solid TumorMalignant solid tumor10027655
- Registration Number
- NL-OMON47049
- Lead Sponsor
- Institut de Recherches Internationales Servier I.R.I.S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 24
- Male or female patients with age * 18 years;
- Histologically or cytologically confirmed diagnosis of advanced/metastatic solid tumour in patients for whom no effective standard therapy is available or suitable;
- For patients participating to the expansion cohort at RP2D , acceptance of pre- and post-treatment biopsies;
- Elapsed time of 4 weeks or, in absence of toxicity, of 5 half-lives between the completion of the prior antineoplastic therapy including biologic, immunologic or targeted anticancer therapy and S 81694 first administration. Elapsed time of 6 weeks for nitrosoureas or mitomycin C;
- Prior radiotherapy is allowed provided that no more than 25% of bone marrow reserve has been irradiated;
- Controlled CNS involvement is accepted as long as therapy with corticosteroids and/or anticonvulsant is not required;
- Resolution (return to baseline) or return to NCI CTCAE Grade * 1 of all acute toxicities due to prior anticancer therapy except alopecia, grade 2 paraesthesia, grade 2 hyper- or hypothyroidism and other non-clinically significant adverse events;
- ECOG (WHO) performance status 0-1 ;
- Effective contraception both for female patients of childbearing potential and male patients with partners of childbearing potential;
- Adequate haematological and blood chemistry measurements
- Pregnancy, breastfeeding or possibility of becoming pregnant or fathering during the study;
- Blood transfusion * 3 weeks before treatment start;
- Episode(s) of clinically relevant active bleeding in the past 3 weeks;
- Known history of haemolytic anaemia (including G6PD deficiency), thrombotic thrombocytopenic purpura (TTP), microangiopathic haemolytic anaemia (MAHA), haemolytic uremic syndrome(HUS);
- Major surgery within 4 weeks before the first day of investigational drug administration without recovery of ECOG 0-1.
- Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis or thrombolysis;
- Clinically significant respiratory or metabolic diseases uncontrolled by medication;
- Patients with uncontrolled high blood pressure;
- Presence of risk factors for torsade de pointes (e.g. heart failure, hypokalaemia, family history of long QT syndrome);
- Patients who have undergone treatment with high-dose chemotherapy requiring progenitor cell transplantation;
- Known active or uncontrolled infections (bacterial, fungal, viral including HBV and HCV infections); patients who are seropositive following HBV vaccine are eligible as well as patients HBV and HCV seropositive, but negative for viral DNA by RT-PCR.
- Known HIV seropositive patients;
- Any known organ dysfunction, serious illness, medical condition, or other medical history, including laboratory abnormalities, which, in the Investigator's opinion, would be likely to interfere with the patient's participation in the study or with the interpretation of the results;
- Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc.) that, in the judgment of the Investigator, may affect the patient's ability to
understand and sign the informed consent and fully comply with all study procedures.
Patients who, within 7 days prior to the first S 81694 intake, are receiving or received strong inducers of FMO1 and FMO3;
Patients who are receiving sensitive CYP3A4 substrates, CYP3A4 and BCRP substrates with narrow therapeutic index (NTI)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>DLT(s) occurring during the first cycle</p><br>
- Secondary Outcome Measures
Name Time Method <p>Safety and tolerability profile characterized by type, frequency, severity,<br /><br>intensity, timing and relationship of adverse events and laboratory<br /><br>abnormalities;<br /><br><br /><br>PK parameters of S 81694 and its metabolite(s);<br /><br><br /><br>Objective tumour response (unconfirmed), as defined by the Response Evaluation<br /><br>Criteria in Solid Tumours (RECIST version 1.1);<br /><br><br /><br>Biomarkers associated with outcome to S 81694.</p><br>