Clinical trial NCT01013324: Study of XL147 (SAR245408) in Advanced or Recurrent Endometrial Carcinoma
Official title: A Phase 2 Study of XL147 (SAR245408) in Subjects With Advanced or Recurrent Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometrial Cancer
Endometrial Neoplasms
Keywords: endometrial cancer
endometrial carcinoma
carcinoma of the endometrium
cancer of the endometrium
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-11-13
Enrollment: 67
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy as defined by overall response rate and progression-free survival (PFS) at 6 months
timeFrame: every 8-10 weeks
measure: Safety of XL147 in the EC population
timeFrame: scheduled evaluations every 2-4 weeks
Secondary outcomes:
measure: Duration of response and PFS
timeFrame: every 8-10 weeks
measure: Characterize pharmacokinetic and pharmacodynamic profiles of XL147
timeFrame: at periodic visits not less than every 4 weeks
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Investigational Site Number 1526
state: California
city: Orlando
country: United States
facility: Investigational Site Number 1532
state: Florida
city: Augusta
country: United States
facility: Investigational Site Number 1239
state: Georgia
city: Boston
country: United States
facility: Investigational Site Number 1133
state: Massachusetts
city: Columbus
country: United States
facility: Investigational Site Number 1325
state: Ohio
city: Oklahoma City
country: United States
facility: Investigational Site Number 1434
state: Oklahoma
city: Abington
country: United States
facility: Investigational Site Number 1132
state: Pennsylvania
city: Philadelphia
country: United States
facility: Investigational Site Number 1134
state: Pennsylvania
city: Providence
country: United States
facility: Investigational Site Number 1142
state: Rhode Island
city: Dallas
country: United States
facility: Investigational Site Number 1527
state: Texas
city: Kortrijk
country: Belgium
facility: Investigational Site Number 3212
city: Leuven
country: Belgium
facility: Investigational Site Number 3211
city: Wilrijk
country: Belgium
facility: Investigational Site Number 3218
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: