Clinical trial NCT00756847: Safety Study of XL147 (SAR245408), in Combination With Paclitaxel and Carboplatin in Adults With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Non-Small Cell Lung Cancer
Endometrial Carcinoma
Ovarian Carcinoma
Keywords: Solid Tumors
NSCLC
Ovarian Cancer
Endometrial Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-09-22
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Assessed at periodic visits
measure: 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
timeFrame: Assessed at periodic visits
Secondary outcomes:
measure: To investigate the relationship between selected biomarkers and efficacy and safety outcomes
timeFrame: Assessed at periodic visits
measure: To assess plasma pharmacokinetics (PK) of XL147, paclitaxel, and carboplatin when used in combination
timeFrame: Assessed at periodic visits
measure: To evaluate preliminary antitumor activity of XL147 in combination with carboplatin and paclitaxel
timeFrame: Assessed at periodic visits
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Investigational Site Number
state: Missouri
city: Oklahoma City
country: United States
facility: Investigational Site Number
state: Oklahoma
city: Houston
country: United States
facility: Investigational Site Number
state: Texas
city: Madison
country: United States
facility: Investigational Site Number
state: Wisconsin
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.