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

NCT ID: NCT01357330

Last Updated: 2016-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2012-06-30

Brief Summary

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

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

Conditions

Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

SAR245408 (XL147)

Intervention Type: DRUG

Pharmaceutical form:capsule and tablet Route of administration: oral

MSC1936369B

Intervention Type: DRUG

Pharmaceutical form:capsule Route of administration: oral

Interventions

SAR245408 (XL147)

Pharmaceutical form:capsule and tablet Route of administration: oral

Intervention Type: DRUG

MSC1936369B

Pharmaceutical form:capsule Route of administration: oral

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840001

Boston, Massachusetts, United States

Investigational Site Number 840002

Boston, Massachusetts, United States

Investigational Site Number 840003

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

U1111-1117-9893

Identifier Type: OTHER

Identifier Source: secondary_id

TCD11742

Identifier Type: -

Identifier Source: org_study_id