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

NCT01013324 | Completed Phase 2 DMC

• 2 other identifiers: ARD11436XL147-201
• Study Type: interventional
• Target: 67
• Locations: 2 countries
• Sites: 13

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.

Conditions

Endometrial Cancer; Endometrial Neoplasms

Keywords

endometrial cancer; endometrial carcinoma; carcinoma of the endometrium; cancer of the endometrium

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Study Arms (1)

Single Arm

EXPERIMENTAL

All subjects will receive single-agent XL147 dosed daily

Drug: XL147 (SAR245408)

Interventions

XL147 (SAR245408) DRUG

dosed as capsules taken orally daily

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (13)

Investigational Site Number 1526

Newport Beach, California, 92663, United States

Location

Investigational Site Number 1532

Orlando, Florida, 32806, United States

Location

Investigational Site Number 1239

Augusta, Georgia, 30912, United States

Location

Investigational Site Number 1133

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number 1325

Columbus, Ohio, 43210, United States

Location

Investigational Site Number 1434

Oklahoma City, Oklahoma, 73084, United States

Location

Investigational Site Number 1132

Abington, Pennsylvania, 19001, United States

Location

Investigational Site Number 1134

Philadelphia, Pennsylvania, 19111, United States

Location

Investigational Site Number 1142

Providence, Rhode Island, 02905, United States

Location

Investigational Site Number 1527

Dallas, Texas, 75230, United States

Location

Investigational Site Number 3212

Kortrijk, 8500, Belgium

Location

Investigational Site Number 3211

Leuven, 3000, Belgium

Location

Investigational Site Number 3218

Wilrijk, 2610, Belgium

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

XL147

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2009
• First Posted: November 13, 2009
• Study Start: January 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: June 3, 2016

Record last verified: 2016-05

Locations

US (10); BE (3)