A Phase I/Ib Trial for the Evaluation of SAR260301 in Monotherapy or in Combination With Vemurafenib in Patients With Various Advanced Cancer
- Registration Number
- NCT01673737
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
Part A - Monotherapy:
- To determine the maximum tolerated dose (MTD) of SAR260301 administered as monotherapy and either on a once or twice daily schedule, to patients with advanced solid tumors or lymphomas.
Part B - Combination:
- To determine the maximum tolerated dose (MTD) of SAR260301 administered in combination with the recommended standard dosage of vemurafenib to patients with unresectable / metastatic v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutated melanoma.
Secondary Objectives:
* To characterize the overall safety and tolerability profile of SAR260301 administered as monotherapy (Part A) and in combination with vemurafenib (Part B).
* To characterize the pharmacokinetic (PK) profile of SAR260301 administered as monotherapy (Part A) and in combination with vemurafenib (Part B) as well as vemurafenib PK in combination with SAR260301 (Part B)
* To evaluate food effect on SAR260301 PK (Part A)
* To assess preliminary antitumor activity according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1 criteria).
* To assess preliminary antitumor activity using volumetric computed tomography (CT) or magnetic resonance imaging(MRI)
* To evaluate the pharmacodynamic (PD) effects of SAR260301 on blood and tumor.
* To evaluate PK/PD relationships.
* To identify the recommended phase 2 dose of SAR260301 in combination with vemurafenib (RP2D) (Part B only)
* To assess potential induction effect of SAR260301 on cytochrome P450 (CYP) isoenzyme 3A (CYP3A) (Part A)
- Detailed Description
Study duration for one patient will include a period for inclusion (screening period) of up to 4 weeks, a treatment period of at least 4 weeks, and a end-of-study visit at 30 days following the last administration of study drug. The patient may continue treatment until disease progression, unacceptable toxicity or willingness to stop, followed by a minimum of 30-days follow-up.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B Combination SAR260301 Dose escalation of twice-daily SAR260301 within a 28-day cycle and in combination with 720 or 960 mg twice daily of Vemurafenib, followed by an expansion phase at the maximal tolerated dose of SAR260301 in combination Part A Monotherapy SAR260301 Dose escalation of daily or twice daily SAR260301 within a 28-day cycle, followed by an expansion phase at the maximal tolerated dose Part B Combination Vemurafenib Dose escalation of twice-daily SAR260301 within a 28-day cycle and in combination with 720 or 960 mg twice daily of Vemurafenib, followed by an expansion phase at the maximal tolerated dose of SAR260301 in combination
- Primary Outcome Measures
Name Time Method Maximal tolerated dose (MTD) of SAR260301 in combination with vemurafenib (Study Part B) Day 28 Maximal tolerated dose (MTD) of SAR260301 in monotherapy (Study Part A) Day 28
- Secondary Outcome Measures
Name Time Method Number of patients with treatment emergent events Up to 2 years Assessment of PK parameters for SAR260301 including tmax, Cmax, AUC fasting and fed (food effect)(Only part A) Up to 8 weeks Assessment of urine excretion of SAR2690301 (Part A) 12-24 hours at Day 28 Assessment of PK parameters for SAR260301 and vemurafenib, including tmax, Cmax, AUC, Rac (Day 28/Day1), half-life, CL, Ctrough 4 weeks Assessment of potential for CYP induction (4beta-hydroxycholesterol)(Part A) Up to 15 days Assessment of PK parameter Rac (Day 28/Day 1) on AUC and Cmax 4 weeks Assessment of PD parameter Serine/threonine protein kinase Akt (AKT) phosphorylation in blood platelets 4 weeks Assessment of PD parameter AKT phosphorylation in tumor (expansion phase only) 15 days Assessment of preliminary antitumor activity as documented by tumor response (defined by RECIST1.1 criteria for solid tumors, international working group (IWG) and revised response for lymphomas, and tumor markers when relevant) Up to 2 years
Trial Locations
- Locations (4)
Investigational Site Number 840001
🇺🇸Boston, Massachusetts, United States
Investigational Site Number 840002
🇺🇸Houston, Texas, United States
Investigational Site Number 840101
🇺🇸Boston, Massachusetts, United States
Investigational Site Number 124001
🇨🇦Toronto, Canada