Track topics on Twitter Track topics that are important to you
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane may fight breast cancer by lowering the amount of estrogen the body makes. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving exemestane together with RO4929097 may kill more breast cancer cells.
PURPOSE: This partially randomized phase I/II trial is studying the side effects and the best dose of RO4929097 when given together with exemestane and to see how well it works compared to exemestane alone in treating premenopausal and postmenopausal patients with advanced or metastatic breast cancer.
- To determine the maximum-tolerated dose or the recommended phase II dose of gamma-secretase inhibitor RO4929097 (RO4929097) in combination with exemestane in pre- and postmenopausal patients with estrogen receptor-positive (ER+) advanced or metastatic breast cancer. (Phase I)
- To determine the safety and tolerability of this regimen in these patients (Phase I)
- To determine the progression-free survival of patients treated with exemestane with versus without RO4929097. (Phase II)
- To determine the overall tumor response rate in patients treated with these regimens. (Phase II)
- To determine the overall survival of patients treated with these regimens. (Phase II)
- To determine the safety of these regimens in these patients. (Phase II)
- To determine the quality of life of patients treated with these regimens. (Exploratory phase II)
- To identify biomarkers of response to treatment or toxicity. (Exploratory phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of gamma-secretase inhibitor RO4929097 followed by a randomized phase II study.
- Phase I: Patients receive oral exemestane* once daily on days 1-21 and oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients are stratified according to menopausal status (pre- vs postmenopausal) and visceral disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive exemestane* as in phase I and oral gamma-secretase inhibitor RO4929097 at the MTD determined in phase I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
- Arm II: Patient receive exemestane* as in arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
NOTE: *In addition to exemestane, pre-menopausal patients receive goserelin subcutaneously every 28 days.
Patients may undergo blood and tissue sample collection for correlative studies.
Patients may complete quality-of-life questionnaires at baseline and periodically during study using the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B).
After completion of study therapy, patients are followed up for 4 weeks and then every 6 months thereafter.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
exemestane, gamma-secretase inhibitor RO4929097, goserelin
Not yet recruiting
National Cancer Institute (NCI)
Published on BioPortfolio: 2014-08-27T03:12:43-0400
RATIONALE: Enzyme inhibitors, such as gamma-secretase inhibitor RO4929097, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I...
RATIONALE: Gamma-secretase inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hy...
RATIONALE: Gamma-secretase inhibitor RO4929097 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I/II clinical trial is study...
This randomized phase I/II clinical trial is studying the side effects and best dose of gamma-secretase/notch signalling pathway inhibitor RO4929097 when given together with vismodegib and...
RATIONALE: Gamma-secretase inhibitor RO4929097 and cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cediranib maleate also may s...
Fulvestrant plus goserelin versus anastrozole plus goserelin versus goserelin alone for hormone receptor-positive, HER2-negative tamoxifen-pretreated premenopausal women with recurrent or metastatic breast cancer (KCSG BR10-04): a multicentre, open-label, three-arm, randomised phase II trial (FLAG study).
We investigated the efficacy and safety of fulvestrant plus goserelin (F + G) versus anastrozole plus goserelin (A + G) in comparison with goserelin (G) alone in premenopausal women with hormone r...
Metastatic breast cancer (MBC) is the leading cause of cancer-related morbidity and mortality among women worldwide. Endocrine therapy is the standard of care for the most common subtype of MBC, hormo...
Non-inferiority in the cumulative castration rate of the 3-month formulation of degarelix compared with the 3-month formulation of goserelin was evaluated in subjects with prostate cancer. A phase III...
The leading cause of cancer death in women around the world is breast cancer. The aromatase inhibitors (AIs) are considered a first-line treatment for estrogen receptor-positive (ER) breast tumors, in...
The PI3K/AKT/mTOR pathway is an oncogenic driver in breast cancer (BC). In this multi-center, pre-surgical study, we evaluated the tissue effects of the AKT inhibitor MK-2206 in women with stage I-III...
A synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE. Goserelin is used in treatments of malignant NEOPLASMS of the prostate, uterine fibromas, and metastatic breast cancer.
Abnormal accumulation of lymph in the arm, shoulder and breast area associated with surgical or radiation breast cancer treatments (e.g., MASTECTOMY).
Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.
A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.
A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)
Endocrine disorders are grouped into two categories: hormone imbalance - when a gland produces too much or too little of an endocrine hormone development of lesions (such as nodules or tumors) in the endocrine system, which may or may not affect...
Track and monitor developments in breast cancer research and commercial development. Follow the tabs above to read the latest global news, research, clinical trials on breast cancer and follow companies active in the development of breast cancer tr...