- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01391533
Study of SAR125844 Single Agent Administered as Slow Intravenous Infusion in Adult Patients With Advanced Malignant Solid Tumors (SARMET)
Dose Escalation, Safety, Pharmacokinetic and Pharmacodynamic, First in Man Study, of SAR125844 Single Agent Administered as Slow Intravenous Infusion in Adult Patients With Advanced Malignant Solid Tumors
Primary Objectives:
To determine the maximum tolerated dose (MTD) of SAR125844. To confirm safety profile of SAR125844 when administered as single agent at the MTD.
To evaluate the preliminary anti-tumoral effect of SAR125844 in patients with MET-gene amplified solid tumors (including sub-group of MET-amplified non-small cell lung cancer [NSCLC] patients) and in patients with Phospho-MET positive tumors without MET-gene amplification.
Secondary Objectives:
To characterize the global safety profile including cumulative toxicities. To evaluate the pharmacokinetic profile of SAR125844 in the proposed dosing schedule(s).
To assess preliminary antitumor activity in patients with measurable/evaluable disease, according to RECIST 1.1 criteria.
To explore the pharmacodynamic effects (PD) of SAR125844. To explore MET gene amplification status in Circulating Tumoral Cells (CTCs) and on tumor biopsies collected during the study, in the escalation part only.
To evaluate other pharmacodynamic biomarkers and help selection of patients who could benefit from SAR125844.
To explore MET-gene amplification status in circulating DNA.
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Dijon, France, 21079
- Investigational Site Number 250002
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Villejuif, France, 94805
- Investigational Site Number 250001
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Bologna, Italy, 40138
- Investigational Site Number 380004
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Milano, Italy, 20133
- Investigational Site Number 380002
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Milano, Italy, 20141
- Investigational Site Number 380001
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Barcelona, Spain, 08035
- Investigational Site Number 724001
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Madrid, Spain, 28040
- Investigational Site Number 724003
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Investigational Site Number 840001
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
In the dose escalation part: patients with high MET tumor expression, evaluable or measurable solid tumors for which no standard therapy is available.
In the expansion cohorts: in the first cohort, patients with diagnosed MET gene amplified including NSCLC patients and measurable tumors for which no standard therapy is available will be eligible. In the second cohort, patients with advanced P-MET positive measurable solid tumor without MET- gene amplification for which no standard therapy is available will be eligible.
Exclusion criteria:
Patient less than 18 years old. ECOG performance status >2. Any serious active disease or co-morbid condition, which, in the opinion of the Investigator, may interfere with the safety or the compliance with the study.
Poor bone marrow reserve as defined by absolute neutrophil count <1.5 x 10^9/L or platelets <100 x 10^9/L.
Poor organ function as defined by one of the following:
- Total bilirubin >1.5 x ULN
- AST, ALT, alkaline phosphatase >2.5 x ULN or >5 x ULN in case of documented liver metastasis. Alkaline phosphatase up to 5 x ULN in case of osteolytic bone metastasis without liver metastases is allowed
- Serum creatinine >1.5 x ULN or
- Serum creatinine between 1.0 and 1.5 x ULN associated with calculated creatinine clearance <60 mL/min
- Proteinuria >500 mg/24H Pregnant or breast-feeding women. No use of effective birth control methods, when applicable. No measurable or evaluable tumor lesion in the Dose Escalation part, and no measurable lesions in the expansion cohorts.
Brain metastasis (other than totally resected or previously pre-irradiated and no progressive/relapsing) or lepto-meningeal carcinomatosis.
No resolution of any specific toxicities (excluding alopecia) related to any prior anti-cancer therapy to grade ≤1 according to the NCI CTCAE v.4.03.
Wash out period of less than 3 weeks from previous antitumor therapy or any investigational treatment (and less than 6 weeks in case of prior nitroso-urea and or mitomycin C treatment).
Any surgery with major risk of bleeding performed less than 10 days prior to study treatment administration.
Any other severe underlying medical conditions, which could impair the ability to participate in the study or the interpretation of its results.
Patients treated with potent CYP3A inhibitor unless it can be discontinued at least 2 weeks prior to study treatment or 5 elimination half-life, whichever is the longest.
Patients treated with potent and moderate CYP3A inducers unless it can be discontinued at least 2 weeks prior to study treatment or 5 elimination half-life, whichever is the longest. Patients treated with weak CYP3A inducers such as dexamethasone are eligible.
Known hypersensitivity or any adverse event related to the study drug excipient.
Prior treatment with any compound in the same class. Mean QTc interval prolongation.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Study Plan
How is the study designed?
Design Details
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dose Escalation
Dose escalation phase: The starting dose of SAR125844 will be 50 mg/m^2 up to 960 mg/m^2
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Pharmaceutical form:solution Route of administration: intravenous |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Dose Escalation To determine the maximum tolerated dose (MTD) of SAR125844
Time Frame: At day 28 of Cycle 1 of each treated patient, DLT is assessed
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At day 28 of Cycle 1 of each treated patient, DLT is assessed
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Expansion Cohorts To evaluate the preliminary anti-tumoral effect of SAR125844
Time Frame: Anticancer activity is assessed at Day 28 and then every 8 weeks thereafter up to an expected maximum of 2 years
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Anticancer activity is assessed at Day 28 and then every 8 weeks thereafter up to an expected maximum of 2 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Number of patients with treatment emergent events
Time Frame: Up to 2 years
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Up to 2 years
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Assessment of PK parameter Cmax
Time Frame: Up to 2 years
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Up to 2 years
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Assessment of PK parameter AUCs
Time Frame: Up to 2 years
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Up to 2 years
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Assessment of PK parameter CL
Time Frame: Up to 2 years
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Up to 2 years
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Assessment of PD parameter ShedMET
Time Frame: Up to 2 years
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Up to 2 years
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Assessment of PD parameter HGF
Time Frame: Up to 2 years
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Up to 2 years
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TED11449
- 2010-021398-36 (EudraCT Number)
- U1111-1117-9878 (Other Identifier: UTN)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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