NCT01391533

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
72

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jul 2011

Longer than P75 for phase_1

Geographic Reach
4 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2011

Completed
5 days until next milestone

First Submitted

Initial submission to the registry

July 6, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

July 12, 2011

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

April 13, 2016

Status Verified

April 1, 2016

Enrollment Period

4.8 years

First QC Date

July 6, 2011

Last Update Submit

April 12, 2016

Conditions

Malignant Solid Tumors

Outcome Measures

Primary Outcomes (2)

  • Dose Escalation To determine the maximum tolerated dose (MTD) of SAR125844

    At day 28 of Cycle 1 of each treated patient, DLT is assessed

  • Expansion Cohorts To evaluate the preliminary anti-tumoral effect of SAR125844

    Anticancer activity is assessed at Day 28 and then every 8 weeks thereafter up to an expected maximum of 2 years

Secondary Outcomes (6)

  • Number of patients with treatment emergent events

    Up to 2 years

  • Assessment of PK parameter Cmax

    Up to 2 years

  • Assessment of PK parameter AUCs

    Up to 2 years

  • Assessment of PK parameter CL

    Up to 2 years

  • Assessment of PD parameter ShedMET

    Up to 2 years

  • +1 more secondary outcomes

Study Arms (1)

Dose Escalation

EXPERIMENTAL

Dose escalation phase: The starting dose of SAR125844 will be 50 mg/m\^2 up to 960 mg/m\^2

Drug: SAR125844

Interventions

SAR125844DRUG

Pharmaceutical form:solution Route of administration: intravenous

Dose Escalation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Investigational Site Number 840001

Boston, Massachusetts, 02114, United States

Location

Investigational Site Number 250002

Dijon, 21079, France

Location

Investigational Site Number 250001

Villejuif, 94805, France

Location

Investigational Site Number 380004

Bologna, 40138, Italy

Location

Investigational Site Number 380002

Milan, 20133, Italy

Location

Investigational Site Number 380001

Milan, 20141, Italy

Location

Investigational Site Number 724001

Barcelona, 08035, Spain

Location

Investigational Site Number 724003

Madrid, 28040, Spain

Location

Related Publications (1)

  • Angevin E, Spitaleri G, Rodon J, Dotti K, Isambert N, Salvagni S, Moreno V, Assadourian S, Gomez C, Harnois M, Hollebecque A, Azaro A, Hervieu A, Rihawi K, De Marinis F. A first-in-human phase I study of SAR125844, a selective MET tyrosine kinase inhibitor, in patients with advanced solid tumours with MET amplification. Eur J Cancer. 2017 Dec;87:131-139. doi: 10.1016/j.ejca.2017.10.016. Epub 2017 Nov 14.

    PMID: 29145039DERIVED

MeSH Terms

Interventions

SAR125844

Study Officials

  • Clinical Sciences & Operations

    Sanofi

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 6, 2011

First Posted

July 12, 2011

Study Start

July 1, 2011

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

April 13, 2016

Record last verified: 2016-04

Locations

US(1)ES(2)IT(3)FR(2)