Phase I, Dose Escalation of SAR125844 in Asian Solid Tumor Patients

Neoplasm Malignant Clinical Trial

— SARMETA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01657214
• Other study ID #: TED12337
• Secondary ID: U1111-1126-7527
• Status: Completed
• Phase: Phase 1
• First received: July 24, 2012
• Last updated: February 16, 2016
• Start date: September 2012
• Est. completion date: January 2016

Study information

• Verified date: February 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm Malignant
• Neoplasms

Intervention

Drug:
• SAR125844
Pharmaceutical form:Concentrate for solution Route of administration: intravenous

Locations

Country	Name	City	State
Japan	Investigational Site Number 392001	Kashiwa-Shi
Japan	Investigational Site Number 392004	Suita-Shi
Japan	Investigational Site Number 392002	Sunto-Gun
Japan	Investigational Site Number 392003	Takatsuki-Shi
Korea, Republic of	Investigational Site Number 410001	Seoul
Korea, Republic of	Investigational Site Number 410002	Seoul
Korea, Republic of	Investigational Site Number 410003	Seoul
Korea, Republic of	Investigational Site Number 410004	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Japan,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	- DOSE ESCALATION To determine the maximum tolerated dose (MTD) of SAR125844		At d28 of Cycle 1 of each treated patient, DLT is assessed	Yes
Primary	- EXPANSION Cohort To evaluate the preliminary anti-tumoral effect of SAR125844		Antitumor activity is assessed at the end of Cycle 1, then every 2 cycles up to treatment discontinuation	No
Secondary	Number of patients with treatment emergent events		Up to a maximum of 2 years	Yes
Secondary	Assessment of PK parameter Cmax		Up to a maximum of 2 years	No
Secondary	Assessment of PK parameter AUCs		Up to a maximum of 2 years	No
Secondary	Assessment of PK parameter CL		Up to a maximum of 2 years	No
Secondary	Assessment of PD parameter ShedMET		Up to a maximum of 2 years	No
Secondary	Assessment of PD parameter HGF		Up to a maximum of 2 years	No