Oral SAR245408 (XL147) and Oral MSC1936369B in Patients With Locally Advanced or Metastatic Solid Tumors

A Phase 1 Dose Escalation Study of Combination Therapy With Oral SAR245408 (XL147) and Oral MSC1936369B in Patients With Locally Advanced or Metastatic Solid Tumors

Primary Objective:

- To determine the maximum tolerated dose(s) (MTD) and the recommended Phase 2 dose(s) (RP2D) of SAR245408 and MSC1936369B when combined in adult subjects with locally advanced or metastatic solid tumors.

Secondary Objective:

• To characterize the safety and tolerability of SAR245408 and MSC1936369B combination therapy administered orally to adult patients with locally advanced or metastatic solid tumors
• To evaluate the pharmacokinetic (PK) profile of SAR245408 and MSC1936369B when used in combination
• To evaluate the pharmacodynamic (PD) effect of the SAR245408/MSC1936369B combination by assessing target and pathway inhibition

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: SAR245408 (XL147); Drug: MSC1936369B

Detailed Description

The duration of the study will include a period for screening of up to a maximum of 28 days, a pretreatment evaluation period of up to 5 days, the on-treatment period, followed by a minimum of 30-day follow-up after the last study drug administration.

The patient may continue study treatment until disease progression, unacceptable toxicity, or consent withdrawal.

The study will have 2 parts:

• Part one - Dose Escalation
• Part Two - Expansion. At the defined maximum tolerated doses (MTD(s), additional patients will be enrolled to collect safety, Pharmacokinetic, and Pharmacodynamic data

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Investigational Site Number 840002
    • Boston, Massachusetts, United States, 02114
      • Investigational Site Number 840001
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Investigational Site Number 840003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

Patient with advanced solid tumors for which there is no approved or curative therapy:

• has any advanced solid tumor with diagnosed alteration in 1 or more genes of the PI3K, and mitogen-activated protein kinase (MAPK) pathways and/or
• has a histologically or cytologically confirmed diagnosis of 1 of the following solid tumors: pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal, breast, ovarian carcinoma and melanoma

Exclusion criteria:

The patient has previously been treated with a PI3K inhibitor or a Mitogen-activated protein extracellular signal-regulated kinase (MEK) inhibitor

The patient has received:

• Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anticancer therapy within 28 days or 5 half lives for noncytotoxics (whichever is shorter) of Day 1 of trial drug treatment (6 weeks for nitrosureas or mitomycin C)
• Any investigational agent within 28 days of Day 1 of trial drug treatment The patient is currently receiving anticoagulation therapy with therapeutic doses of warfarin (low-dose warfarin ≤1 mg/day, heparin, and low-molecular weight heparins are permitted) History of central nervous system metastases The patient has had congestive heart failure, unstable angina, a myocardial infarction, cardiac conduction abnormality or pacemaker or a stroke within 3 months of entering the study. The patient has retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis, or history of retinal vein occlusion, or has medically relevant abnormalities identified on screening ophthalmologic examination.

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

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Dose escalation phase The starting dose of SAR245408 will be 25-mg once daily (up to 200-mg). The starting dose of MSC1936369B will be 15- mg once daily (up to 90-mg)	Drug: SAR245408 (XL147); Pharmaceutical form:capsule and tablet Route of administration: oral; Drug: MSC1936369B; Pharmaceutical form:capsule Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification of maximum tolerated dose	up to 4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment emergent adverse events	up to 4 years
Pharmakokinetic parameters of SAR245408: Cmax	up to 4 years
Pharmakokinetic parameters of SAR245408: Tmax	up to 4 years
Pharmakokinetic parameters of SAR245408:AUCι	up to 4 years
Pharmakokinetic parameters of MSC1936369B: Cmax	up to 4 years
Pharmakokinetic parameters of MSC1936369B: Tmax	up to 4 years
Pharmakokinetic parameters of MSC1936369B: AUCι	up to 4 years

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: May 16, 2011
• First Submitted That Met QC Criteria: May 19, 2011
• First Posted (Estimate): May 20, 2011

Study Record Updates

• Last Update Posted (Estimate): April 1, 2016
• Last Update Submitted That Met QC Criteria: March 31, 2016
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: locally advanced or metastatic
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TCD11742; U1111-1117-9893 (Other Identifier: UTN)