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

Endometrial Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01013324
• Other study ID #: ARD11436
• Secondary ID: XL147-201
• Status: Completed
• Phase: Phase 2
• First received: November 10, 2009
• Last updated: March 31, 2016
• Start date: January 2010
• Est. completion date: March 2013

Study information

• Verified date: March 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• XL147 (SAR245408)
dosed as capsules taken orally daily

Locations

Country	Name	City	State
Belgium	Investigational Site Number 3212	Kortrijk
Belgium	Investigational Site Number 3211	Leuven
Belgium	Investigational Site Number 3218	Wilrijk
United States	Investigational Site Number 1132	Abington	Pennsylvania
United States	Investigational Site Number 1239	Augusta	Georgia
United States	Investigational Site Number 1133	Boston	Massachusetts
United States	Investigational Site Number 1325	Columbus	Ohio
United States	Investigational Site Number 1527	Dallas	Texas
United States	Investigational Site Number 1526	Newport Beach	California
United States	Investigational Site Number 1434	Oklahoma City	Oklahoma
United States	Investigational Site Number 1532	Orlando	Florida
United States	Investigational Site Number 1134	Philadelphia	Pennsylvania
United States	Investigational Site Number 1142	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy as defined by overall response rate and progression-free survival (PFS) at 6 months		every 8-10 weeks	No
Primary	Safety of XL147 in the EC population		scheduled evaluations every 2-4 weeks	Yes
Secondary	Duration of response and PFS		every 8-10 weeks	No
Secondary	Characterize pharmacokinetic and pharmacodynamic profiles of XL147		at periodic visits not less than every 4 weeks	No