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

NCT01357330 | Completed Phase 1

• 2 other identifiers: TCD11742U1111-1117-9893
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

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

Conditions

Solid Tumors

Keywords

locally advanced or metastatic

Outcome Measures

Primary Outcomes (1)

• Identification of maximum tolerated dose

  up to 4 years

Secondary Outcomes (7)

• 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

Study Arms (1)

Dose Escalation

EXPERIMENTAL

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); Drug: MSC1936369B

Interventions

SAR245408 (XL147) DRUG

Pharmaceutical form:capsule and tablet Route of administration: oral

Dose Escalation

MSC1936369B DRUG

Pharmaceutical form:capsule Route of administration: oral

Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (3)

Investigational Site Number 840001

Boston, Massachusetts, 02114, United States

Location

Investigational Site Number 840002

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number 840003

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

XL147

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2011
• First Posted: May 20, 2011
• Study Start: May 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: April 1, 2016

Record last verified: 2012-08

Locations

US (3)