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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01357330
• Other study ID #: TCD11742
• Secondary ID: U1111-1117-9893
• Status: Completed
• Phase: Phase 1
• First received: May 16, 2011
• Last updated: March 31, 2016
• Start date: May 2011
• Est. completion date: June 2012

Study information

• Verified date: August 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• SAR245408 (XL147)
Pharmaceutical form:capsule and tablet Route of administration: oral
• MSC1936369B
Pharmaceutical form:capsule Route of administration: oral

Locations

Country	Name	City	State
United States	Investigational Site Number 840001	Boston	Massachusetts
United States	Investigational Site Number 840002	Boston	Massachusetts
United States	Investigational Site Number 840003	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of maximum tolerated dose		up to 4 years	No
Secondary	Number of participants with treatment emergent adverse events		up to 4 years	Yes
Secondary	Pharmakokinetic parameters of SAR245408: Cmax		up to 4 years	No
Secondary	Pharmakokinetic parameters of SAR245408: Tmax		up to 4 years	No
Secondary	Pharmakokinetic parameters of SAR245408:AUC?		up to 4 years	No
Secondary	Pharmakokinetic parameters of MSC1936369B: Cmax		up to 4 years	No
Secondary	Pharmakokinetic parameters of MSC1936369B: Tmax		up to 4 years	No
Secondary	Pharmakokinetic parameters of MSC1936369B: AUC?		up to 4 years	No