Study of XL147 (SAR245408) or XL765 (SAR245409) in Combination With Letrozole in Subjects With Breast Cancer

NCT ID: NCT01082068

Last Updated: 2016-06-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Study Completion Date

2013-04-30

Brief Summary

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Phase 1 of this study will evaluate the maximum tolerated dose (MTD) of XL147 when given in combination with letrozole (Femara) and of XL765 when given in combination with letrozole. After the MTD is established for each combination (Phase 2), subjects will be enrolled to evaluate the preliminary efficacy and safety of these combinations in subjects with breast cancer refractory to a non-steroidal aromatase inhibitor that is ER+/PGR+ and HER2-. Letrozole is used in the treatment of different types of breast cancer, but patients can develop resistance.

Upregulation of PI3K activity is one of the most common characteristics of human cancer cells, including breast tumor cells. Activation of PI3K results in stimulation of AKT and mTOR kinases, resulting in the promotion of tumor cell proliferation and survival. Preclinical and retrospective clinical data suggest that aberrant activation of the PI3K pathway may play a role in aromatase inhibitor resistance in patients with ER+, HER2- breast cancer. XL147 is a potent inhibitor of PI3K, and XL765 is a potent dual inhibitor of PI3K and mTOR; therefore either of these compounds in combination with letrozole warrants clinical investigation.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

XL147 (SAR245408) + letrozole

Group Type EXPERIMENTAL

XL147 (SAR245408)

Intervention Type DRUG

given orally once daily as tablets

letrozole (Femara)

Intervention Type DRUG

given orally once daily as tablets

Arm 2

XL765 + letrozole

Group Type EXPERIMENTAL

XL765 (SAR245409)

Intervention Type DRUG

given orally twice daily as capsules

letrozole (Femara)

Intervention Type DRUG

given orally once daily as tablets

Interventions

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XL147 (SAR245408)

given orally once daily as tablets

Intervention Type DRUG

XL765 (SAR245409)

given orally twice daily as capsules

Intervention Type DRUG

letrozole (Femara)

given orally once daily as tablets

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* The subject has histologically confirmed breast cancer that is ER+ and/or PGR+.
* The subject's breast cancer is negative for HER2.
* The subject has recurrent or metastatic breast cancer that is refractory to a nonsteroidal aromatase inhibitor and has either disease progression or disease recurrence.
* Subjects previously treated with letrozole must be able to tolerate the approved dose and schedule of letrozole.
* For subjects enrolled in Phase 2, either archival tumor samples must be available, or the subject must be willing to undergo a fresh biopsy.
* In Phase 2, at least 30 subjects in each arm must have measurable disease
* The subject is a postmenopausal female.
* If a subject is currently receiving bisphosphonates, the subject must have received the bisphosphonates for at least 2 months before starting study treatment.
* The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
* The subject has adequate organ and marrow function.
* The subject has no other diagnosis of malignancy or evidence of other malignancy for 2 years before screening for this study (except non-melanoma skin cancer or in situ carcinoma of the cervix).
* The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.

Exclusion Criteria

* The subject has received prior treatment with a selective inhibitor of PI3K, AKT, and/or mTOR.
* Certain restrictions on prior therapies apply.
* The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline.
* The subject has untreated, symptomatic, or progressive brain metastases.
* The subject has only non-measurable lesions, other than bone, skin, or chest wall metastasis
* The subject has to start cytotoxic chemotherapy due to rapid progressive disease involving major organs.
* The subject has prothrombin time/ International Normalized Ratio (PT/ 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 (QTc) \> 470 ms.
* The subject has a diagnosis of uncontrolled diabetes mellitus.
* The subject is known to be positive for the human immunodeficiency virus (HIV).
* The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation(s).
* The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Investigational Site Number 1537

Los Angeles, California, United States

Site Status

Investigational Site Number 1601

Denver, Colorado, United States

Site Status

Investigational Site Number 1238

Fort Meyers, Florida, United States

Site Status

Investigational Site Number 1441

Chicago, Illinois, United States

Site Status

Investigational Site Number 1138

Boston, Massachusetts, United States

Site Status

Investigational Site Number 1331

Ann Arbor, Michigan, United States

Site Status

Investigational Site Number 1330

Detroit, Michigan, United States

Site Status

Investigational Site Number 5201

Columbia, Missouri, United States

Site Status

Investigational Site Number 1252

Durham, North Carolina, United States

Site Status

Investigational Site Number 1214

Nashville, Tennessee, United States

Site Status

Investigational Site Number 5246

El Paso, Texas, United States

Site Status

Investigational Site Number 3321

Nantes Saint Herblain, , France

Site Status

Investigational Site Number 3324

Paris, , France

Site Status

Investigational Site Number 3415

Barcelona, , Spain

Site Status

Investigational Site Number 3419

Barcelona, , Spain

Site Status

Investigational Site Number 3413

Madrid, , Spain

Site Status

Investigational Site Number 3420

Madrid, , Spain

Site Status

Countries

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United States France Spain

Other Identifiers

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XL147-202

Identifier Type: OTHER

Identifier Source: secondary_id

ARD11437

Identifier Type: -

Identifier Source: org_study_id

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