Phase I, Dose Escalation of SAR125844 in Asian Solid Tumor Patients (SARMETA)
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).
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|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|
- - DOSE ESCALATION To determine the maximum tolerated dose (MTD) of SAR125844 [ Time Frame: At d28 of Cycle 1 of each treated patient, DLT is assessed ]
- - EXPANSION Cohort To evaluate the preliminary anti-tumoral effect of SAR125844 [ Time Frame: Antitumor activity is assessed at the end of Cycle 1, then every 2 cycles up to treatment discontinuation ]
- Number of patients with treatment emergent events [ Time Frame: Up to a maximum of 2 years ]
- Assessment of PK parameter Cmax [ Time Frame: Up to a maximum of 2 years ]
- Assessment of PK parameter AUCs [ Time Frame: Up to a maximum of 2 years ]
- Assessment of PK parameter CL [ Time Frame: Up to a maximum of 2 years ]
- Assessment of PD parameter ShedMET [ Time Frame: Up to a maximum of 2 years ]
- Assessment of PD parameter HGF [ Time Frame: Up to a maximum of 2 years ]
|Study Start Date:||September 2012|
|Study Completion Date:||January 2016|
|Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: Dose escalation
SAR125844 will be administered as weekly IV infusion. Four weekly administrations are considered as 1 cycle. The starting dose will be either 1 dose level (DL) below the highest cleared dose level in a European TED11449 ongoing study or DL4 (260 mg/m^2), if the highest cleared dose in TED11449 is >340 mg/m^2.
Pharmaceutical form:Concentrate for solution
Route of administration: intravenous
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01657214
|Investigational Site Number 392001|
|Investigational Site Number 392004|
|Investigational Site Number 392002|
|Investigational Site Number 392003|
|Korea, Republic of|
|Investigational Site Number 410001|
|Seoul, Korea, Republic of, 110-744|
|Investigational Site Number 410004|
|Seoul, Korea, Republic of, 120-752|
|Investigational Site Number 410003|
|Seoul, Korea, Republic of, 135-710|
|Investigational Site Number 410002|
|Seoul, Korea, Republic of, 138-736|
|Study Director:||Clinical Sciences & Operations||Sanofi|