Clinical trial NCT01657214: Phase I, Dose Escalation of SAR125844 in Asian Solid Tumor Patients
Official title: Phase I, Dose Escalation Study of Safety, Pharmacokinetic and Pharmacodynamic of SAR125844 Administered Weekly as Intravenous Infusion in Asian Adult Patients With Advanced Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasm Malignant
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-08-06
Enrollment: 70
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

In the dose escalation: to determine the maximum tolerated dose (MTD) of SAR125844.

In the expansion cohort: to evaluate the preliminary anti-tumoral effect of SAR125844 in patients with measurable and MET gene amplification (including gastric cancer patients).

Secondary Objectives:

To characterize and confirm the global safety profile of SAR125844 including cumulative toxicities.

To assess preliminary antitumor activity of SAR125844. To explore the pharmacodynamic effects (PDy) of SAR125844. To evaluate the pharmacokinetic profile of SAR125844. To explore the relationship of MET gene amplification status with antitumor effects.

To evaluate other pharmacodynamic biomarkers.

Detailed description: For both cohorts, escalation and expansion, the duration of the study for one patient will include a period for inclusion of up to 3 weeks and a 4-week treatment cycle(s).The patient may continue treatment until disease progression, unacceptable toxicity or willingness to stop, followed by a minimum of 30-days follow-up.

If a patient treated in dose escalation part or in an expansion cohort, continues to benefit from the treatment at the time of Clinical Study Report, the patient can continue study treatment for a maximum of 1 year and will continue to undergo all assessments as per the study flowchart. Such patients will be followed at least until 30 days after the last IMP administration.

Eligibility criteria: Inclusion criteria:

* Patients with solid tumor for which no standard therapy is available.
* At the recommended dose (expansion cohort): only patients with measurable disease and MET gene amplification.

Exclusion criteria:

* Patient less than 20 years old.
* ECOG performance status \>2.
* Poor bone marrow reserve as defined by absolute neutrophils 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.
* 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 \>500mg/24h.
* Pregnant or breast-feeding women.
* Sexually active (males and females) who do not agree to use medically acceptable methods of contraception during the course of the study and for 3 months following discontinuation of study drug.
* Female patients of childbearing potential must have a negative pregnancy test at screening.
* Known or symptomatic 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 nitrozo-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.
* Patients treated with potent CYP3A inhibitor.
* Patients treated with potent and moderate CYP3A inducers.
* Known hypersensitivity or any adverse event related to the study drug excipient (Captisol®).
* Prior treatment with any MET inhibitor compound (selective or not).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: - DOSE ESCALATION To determine the maximum tolerated dose (MTD) of SAR125844
timeFrame: At d28 of Cycle 1 of each treated patient, DLT is assessed
measure: - EXPANSION Cohort To evaluate the preliminary anti-tumoral effect of SAR125844
timeFrame: Antitumor activity is assessed at the end of Cycle 1, then every 2 cycles up to treatment discontinuation
Secondary outcomes:
measure: Number of patients with treatment emergent events
timeFrame: Up to a maximum of 2 years
measure: Assessment of PK parameter Cmax
timeFrame: Up to a maximum of 2 years
measure: Assessment of PK parameter AUCs
timeFrame: Up to a maximum of 2 years
measure: Assessment of PK parameter CL
timeFrame: Up to a maximum of 2 years
measure: Assessment of PD parameter ShedMET
timeFrame: Up to a maximum of 2 years
measure: Assessment of PD parameter HGF
timeFrame: Up to a maximum of 2 years
Other outcomes:
Locations:
city: Kashiwa-Shi
country: Japan
facility: Investigational Site Number 392001
city: Suita-Shi
country: Japan
facility: Investigational Site Number 392004
city: Sunto-Gun
country: Japan
facility: Investigational Site Number 392002
city: Takatsuki-Shi
country: Japan
facility: Investigational Site Number 392003
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410001
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410004
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410003
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: