Study of XL147 (SAR245408) in Advanced or Recurrent Endometrial Carcinoma

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT01013324

Collaborator

(none)

Enrollment

Locations

Arm

37.9

Duration (Months)

5.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There has not been any systemic therapy approved in the United States or in Europe for treating advanced or recurrent endometrial cancer (EC). This study will evaluate the safety and preliminary efficacy of XL147 in advanced or recurrent EC.

Constitutively active phosphatidylinositol-3 kinase (PI3K)/phosphatase and tensin homolog on chromosome 10 (PTEN) pathway signaling is common in EC and involved in the development and/or progression of the disease. PTEN deficiency and/or activating mutations/amplification in the PIK3CA gene that encodes the p110α catalytic subunit of PI3K have been frequently detected in EC patients. XL147 is a potent and highly selective inhibitor of the Class I PI3K family of lipid kinases. In addition, in vivo preclinical data have demonstrated that XL147 targets both proximal and distal signaling in the PI3K/PTEN pathway. Therefore, XL147 may have utility in the treatment of subjects with advanced or recurrent EC.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Cancer Endometrial Neoplasms	Drug: XL147 (SAR245408)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

67 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Study of XL147 (SAR245408) in Subjects With Advanced or Recurrent Endometrial Carcinoma

Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Arm All subjects will receive single-agent XL147 dosed daily	Drug: XL147 (SAR245408) dosed as capsules taken orally daily

Arm

Intervention/Treatment

Experimental: Single Arm

All subjects will receive single-agent XL147 dosed daily

Drug: XL147 (SAR245408)

dosed as capsules taken orally daily

Outcome Measures

Primary Outcome Measures

Efficacy as defined by overall response rate and progression-free survival (PFS) at 6 months [every 8-10 weeks]
Safety of XL147 in the EC population [scheduled evaluations every 2-4 weeks]

Secondary Outcome Measures

Duration of response and PFS [every 8-10 weeks]
Characterize pharmacokinetic and pharmacodynamic profiles of XL147 [at periodic visits not less than every 4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

The subject has a histologically confirmed diagnosis of EC (endometrioid, serous, clear cell adenocarcinoma, adenosquamous carcinoma, or mixed histology, any grade) that is advanced (ie, persistent, locally advanced) or recurrent, and is incurable by standard therapies and has received one platinum based chemotherapy regimen for EC.
The subject is at least 18 years old.
The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
The subject has at least one measurable lesion
Tissue samples from archival or fresh tissue, or a tissue block of the subject's tumor
The subject has adequate organ and marrow function
The subject is capable of understanding the informed consent and complying with the protocol and has signed the informed consent document before any study-specific screening procedures or evaluations are performed.
Sexually active subjects of childbearing potential and their partners must agree to use medically accepted methods of contraception during the course of the study and for 3 months after discontinuation of study drug.
Subjects of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

The subject has previously been treated with a selective PI3K inhibitor, mTOR inhibitor, or AKT inhibitor.
The subject has uterine sarcomas (leiomyosarcoma), mixed Mullerian tumors, squamous carcinoma of the uterus, and/or adenosarcomas of the uterus.
Certain restrictions on prior treatments apply
The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline (excluding alopecia and peripheral neuropathy).
The subject has a known primary brain tumor or brain metastasis.
The subject has any other diagnosis of malignancy or evidence of malignancy (except non-melanoma skin cancer or in situ carcinoma of the cervix) within 2 years before screening for this study.
The subject has a diagnosis of uncontrolled diabetes mellitus or has a fasting plasma glucose > 160 mg/dL.
The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤ 1 mg/day is permitted).
The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test results at screening that are above 1.3 x the laboratory upper limit of normal.
The subject has uncontrolled, significant intercurrent illness
The subject has a baseline corrected QT interval ≥ 470 ms.
The subject is known to be positive for the human immunodeficiency virus (HIV). (Note: Baseline HIV screening is not required.)
The subject is pregnant or breastfeeding.
The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 1526	Newport Beach	California	United States	92663
2	Investigational Site Number 1532	Orlando	Florida	United States	32806
3	Investigational Site Number 1239	Augusta	Georgia	United States	30912
4	Investigational Site Number 1133	Boston	Massachusetts	United States	02115
5	Investigational Site Number 1325	Columbus	Ohio	United States	43210
6	Investigational Site Number 1434	Oklahoma City	Oklahoma	United States	73084
7	Investigational Site Number 1132	Abington	Pennsylvania	United States	19001
8	Investigational Site Number 1134	Philadelphia	Pennsylvania	United States	19111
9	Investigational Site Number 1142	Providence	Rhode Island	United States	02905
10	Investigational Site Number 1527	Dallas	Texas	United States	75230
11	Investigational Site Number 3212	Kortrijk		Belgium	8500
12	Investigational Site Number 3211	Leuven		Belgium	3000
13	Investigational Site Number 3218	Wilrijk		Belgium	2610