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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01657214
First received: July 24, 2012
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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.

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 anti-tumor effects.

To evaluate other pharmacodynamic biomarkers.


Condition Intervention Phase
Neoplasm Malignant
Drug: SAR125844
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I, Dose Escalation Study of Safety, Pharmacokinetic and Pharmaco-Dynamic of SAR125844 Administered Weekly as Intravenous Infusion in Asian Adult Patients With Advanced Malignant Solid Tumors

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Expansion cohort 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of patients with treatment emergent events [ Time Frame: Up to a maximum of 2 years ] [ Designated as safety issue: Yes ]
  • Assessment of PK parameter Cmax [ Time Frame: Up to a maximum of 2 years ] [ Designated as safety issue: No ]
  • Assessment of PK parameter AUCs [ Time Frame: Up to a maximum of 2 years ] [ Designated as safety issue: No ]
  • Assessment of PK parameter CL [ Time Frame: Up to a maximum of 2 years ] [ Designated as safety issue: No ]
  • Assessment of PD parameter ShedMET [ Time Frame: Up to a maximum of 2 years ] [ Designated as safety issue: No ]
  • Assessment of PD parameter HGF [ Time Frame: Up to a maximum of 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose escalation
SAR125844 will be administered as weekly IV infusion. Four weekly administrations are considered as 1 cycle. The starting dose is 260mg/m2.
Drug: SAR125844

Pharmaceutical form:Concentrate for solution

Route of administration: intravenous


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

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 109/L or platelets < 100 x 109/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 UNL 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 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01657214

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
Japan
Investigational Site Number 392001 Recruiting
Kashiwa-Shi, Japan
Investigational Site Number 392002 Recruiting
Sunto-Gun, Japan
Korea, Republic of
Investigational Site Number 410001 Recruiting
Seoul, Korea, Republic of, 110-744
Investigational Site Number 410002 Recruiting
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01657214     History of Changes
Other Study ID Numbers: TED12337, U1111-1126-7527
Study First Received: July 24, 2012
Last Updated: June 19, 2014
Health Authority: Korea: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on August 19, 2014