Safety Study of XL147 (SAR245408), in Combination With Paclitaxel and Carboplatin in Adults With Solid Tumors
Primary Purpose
Cancer, Non-Small Cell Lung Cancer, Endometrial Carcinoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
XL147 (SAR245408),
paclitaxel
carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Cancer focused on measuring Solid Tumors, NSCLC, Ovarian Cancer, Endometrial Cancer
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
Sites / Locations
- Investigational Site Number
- Investigational Site Number
- Investigational Site Number
- Investigational Site Number
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
To investigate the relationship between selected biomarkers and efficacy and safety outcomes
To assess plasma pharmacokinetics (PK) of XL147, paclitaxel, and carboplatin when used in combination
To evaluate preliminary antitumor activity of XL147 in combination with carboplatin and paclitaxel
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00756847
Brief Title
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
2. Study Status
Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
September 2008 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
October 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Non-Small Cell Lung Cancer, Endometrial Carcinoma, Ovarian Carcinoma
Keywords
Solid Tumors, NSCLC, Ovarian Cancer, Endometrial Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
XL147 (SAR245408),
Intervention Description
Gelatin capsules supplied in 25- and 100-mg strengths; daily dosing
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Other Intervention Name(s)
Taxol®
Intervention Description
Intravenous injection dosed once every three weeks
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
Intravenous injection dosed once every three weeks
Primary Outcome Measure Information:
Title
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
Time Frame
Assessed at periodic visits
Title
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
Time Frame
Assessed at periodic visits
Secondary Outcome Measure Information:
Title
To investigate the relationship between selected biomarkers and efficacy and safety outcomes
Time Frame
Assessed at periodic visits
Title
To assess plasma pharmacokinetics (PK) of XL147, paclitaxel, and carboplatin when used in combination
Time Frame
Assessed at periodic visits
Title
To evaluate preliminary antitumor activity of XL147 in combination with carboplatin and paclitaxel
Time Frame
Assessed at periodic visits
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Investigational Site Number
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Investigational Site Number
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Investigational Site Number
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-6164
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28275119
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.
Results Reference
derived
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Safety Study of XL147 (SAR245408), in Combination With Paclitaxel and Carboplatin in Adults With Solid Tumors
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