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

NCT00756847 | Completed Phase 1

• 2 other identifiers: TED11435XL147-003
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 4

Brief 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).

Conditions

Cancer; Non-Small Cell Lung Cancer; Endometrial Carcinoma; Ovarian Carcinoma

Keywords

Solid Tumors; NSCLC; Ovarian Cancer; Endometrial Cancer

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (3)

• To investigate the relationship between selected biomarkers and efficacy and safety outcomes

  Assessed at periodic visits

• To assess plasma pharmacokinetics (PK) of XL147, paclitaxel, and carboplatin when used in combination

  Assessed at periodic visits

• To evaluate preliminary antitumor activity of XL147 in combination with carboplatin and paclitaxel

  Assessed at periodic visits

Study Arms (1)

1

EXPERIMENTAL

Drug: XL147 (SAR245408),; Drug: paclitaxel; Drug: carboplatin

Interventions

XL147 (SAR245408), DRUG

Gelatin capsules supplied in 25- and 100-mg strengths; daily dosing

1

paclitaxel DRUG

Intravenous injection dosed once every three weeks

Also known as: Taxol®

1

carboplatin DRUG

Intravenous injection dosed once every three weeks

1

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (4)

Investigational Site Number

St Louis, Missouri, 63110, United States

Location

Investigational Site Number

Oklahoma City, Oklahoma, 73104, United States

Location

Investigational Site Number

Houston, Texas, 77030-4009, United States

Location

Investigational Site Number

Madison, Wisconsin, 53792-6164, United States

Location

Related Publications (1)

• Wheler J, Mutch D, Lager J, Castell C, Liu L, Jiang J, Traynor AM. Phase I Dose-Escalation Study of Pilaralisib (SAR245408, XL147) in Combination with Paclitaxel and Carboplatin in Patients with Solid Tumors. Oncologist. 2017 Apr;22(4):377-e37. doi: 10.1634/theoncologist.2016-0257. Epub 2017 Mar 8.

  PMID: 28275119 DERIVED

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung; Endometrial Neoplasms; Ovarian Neoplasms

Interventions

XL147; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 18, 2008
• First Posted: September 22, 2008
• Study Start: September 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: October 1, 2012
• Last Updated: April 10, 2013

Record last verified: 2013-04

Locations

US (4)