Safety Study of XL147 (SAR245408), in Combination With Paclitaxel and Carboplatin in Adults With Solid Tumors

Cancer Clinical Trial

Official title:

A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL147 (SAR245408) in Combination With Paclitaxel and Carboplatin in Subjects With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00756847
• Other study ID #: TED11435
• Secondary ID: XL147-003
• Status: Completed
• Phase: Phase 1
• First received: September 18, 2008
• Last updated: April 9, 2013
• Start date: September 2008
• Est. completion date: October 2012

Study information

• Verified date: April 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and tolerability of XL147 in combination with paclitaxel and carboplatin in adults with solid tumors. XL147 is a new chemical entity that inhibits PI3 Kinase. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells. In clinical practice, the combination of paclitaxel and carboplatin is an accepted treatment regimen for various solid tumors, including ovarian cancer, endometrial cancer and non-small cell lung cancer (NSCLC).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: October 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of:

• Advanced solid tumor that is no longer responding to therapies OR

• Advanced or recurrent endometrial carcinoma OR

• Advanced or recurrent ovarian carcinoma OR

• Unresectable (Stage IIIB or IV) NSCLC

• ECOG Performance Status 0-1 (ECOG status of 2 may be considered following discussion and agreement with sponsor)

• Adequate organ and bone marrow function as defined by hematological and serum chemistry limits

• At least 18 years old

• Both men and women must practice adequate contraception

• Informed consent

Exclusion Criteria:

• Restriction of some therapies/medications within specific timeframes prior to enrollment and during the study including prior therapy with PI3K, AKT, or mTOR inhibitors, cytotoxic chemotherapy, biologic agents, nitrosoureas or mitomycin C, small-molecule kinase inhibitors, non-cytotoxic hormonal agents

• Known allergy or hypersensitivity to any of the components of the treatment formulations

• Taking oral corticosteroids chronically or > 1 mg/day warfarin

• Not recovered from the toxic effects of prior therapy

• History of diabetes mellitus.

• Uncontrolled intercurrent illness

• Pregnant or breastfeeding

• Congestive heart failure, unstable angina, or a myocardial infarction within 3 months of entering the study.

• HIV positive

• Diagnosis of another malignancy may exclude subject from study

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Endometrial Carcinoma
• Endometrial Neoplasms
• Non-Small Cell Lung Cancer
• Ovarian Carcinoma
• Ovarian Neoplasms

Intervention

Drug:
• XL147 (SAR245408),
Gelatin capsules supplied in 25- and 100-mg strengths; daily dosing
• paclitaxel
Intravenous injection dosed once every three weeks
• carboplatin
Intravenous injection dosed once every three weeks

Locations

Country	Name	City	State
United States	Investigational Site Number	Houston	Texas
United States	Investigational Site Number	Madison	Wisconsin
United States	Investigational Site Number	Oklahoma City	Oklahoma
United States	Investigational Site Number	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the safety, tolerability, and MTD of XL147 administered in combination with paclitaxel (at doses up to 175 mg/m2) and carboplatin in subjects with advanced solid tumors		Assessed at periodic visits	Yes
Primary	To evaluate the safety, tolerability, and MTD of XL147 administered in combination with paclitaxel (at doses up to 225 mg/m2) and carboplatin in subjects with NSCLC		Assessed at periodic visits	Yes
Secondary	To investigate the relationship between selected biomarkers and efficacy and safety outcomes		Assessed at periodic visits	No
Secondary	To assess plasma pharmacokinetics (PK) of XL147, paclitaxel, and carboplatin when used in combination		Assessed at periodic visits	No
Secondary	To evaluate preliminary antitumor activity of XL147 in combination with carboplatin and paclitaxel		Assessed at periodic visits	No