A Phase II Trial of Endocrine Therapy in Combination With OSI-906 (an IGF-1R Inhibitor) With or Without Erlotinib (Tarceva, an EGFR Inhibitor) in Patients With Hormone-sensitive Metastatic Breast Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Time to progression
研究概览
简要总结
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole +/- goserelin (the latter for pre-menopausal women only) may fight breast cancer by lowering the amount of estrogen the body makes. OSI-906 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether hormone therapy and OSI-906 are more effective when given with or without erlotinib hydrochloride in treating hormone-sensitive metastatic breast cancer.
PURPOSE: This phase II trial is studying how well giving hormone therapy together with OSI-906 with or without erlotinib hydrochloride works in treating hormone-sensitive patients with metastatic breast cancer.
详细描述
OBJECTIVES:
Primary
- To determine the antitumor activity of letrozole +/- goserelin (the latter for pre-menopausal women only) in combination with IGF-1R inhibitor OSI-906 with or without erlotinib hydrochloride, measured by time to progression, in patients with hormone-sensitive metastatic breast cancer.
Secondary
- To determine the safety of these regimens in these patients.
- To determine the response rate in patients treated with these regimens.
- To measure circulating C-peptide, IGF-1, and IGFBP-3 levels in patients treated with these regimens.
- To correlate the expression of IGF-IR, EGFR, HER2, Y1316 and Y1131 pIGF-1R, PTEN, S473 pAkt, pMAPK, S118 (MAPK site), and S167 (Akt and S6 site) pER in formalin-fixed paraffin blocks (FFPB) with clinical outcome and luminal A vs. luminal B subtypes of breast cancer.
- To correlate the mutational status of PI3K (E542K, E545K, H1047R) in DNA extracted from FFPB or fresh biopsy with clinical outcome and luminal A vs. luminal B subtypes of breast cancer
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Letrozole +/-goserelin, OSI-906 (Arm I )
Patients receive oral letrozole once daily on days 1-28 plus subcutaneous goserelin (the latter for pre-menopausal women only) on day 1 and oral IGF-1R inhibitor OSI-906 twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: IGF-1R inhibitor OSI-906 (Drug)
Letrozole +/-goserelin, OSI-906 (Arm I )
Patients receive oral letrozole once daily on days 1-28 plus subcutaneous goserelin (the latter for pre-menopausal women only) on day 1 and oral IGF-1R inhibitor OSI-906 twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: goserelin (Drug)
Letrozole +/-goserelin, OSI-906 (Arm I )
Patients receive oral letrozole once daily on days 1-28 plus subcutaneous goserelin (the latter for pre-menopausal women only) on day 1 and oral IGF-1R inhibitor OSI-906 twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: letrozole (Drug)
Letrozole +/- goserelin, OSI-906, erlotinib (Arm II)
Patients receive oral letrozole and subcutaneous goserelin (the latter for pre-menopausal women only) and oral IGF-1R inhibitor OSI-906 as in arm I. Patients also receive oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: IGF-1R inhibitor OSI-906 (Drug)
Letrozole +/- goserelin, OSI-906, erlotinib (Arm II)
Patients receive oral letrozole and subcutaneous goserelin (the latter for pre-menopausal women only) and oral IGF-1R inhibitor OSI-906 as in arm I. Patients also receive oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: erlotinib hydrochloride (Drug)
Letrozole +/- goserelin, OSI-906, erlotinib (Arm II)
Patients receive oral letrozole and subcutaneous goserelin (the latter for pre-menopausal women only) and oral IGF-1R inhibitor OSI-906 as in arm I. Patients also receive oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: goserelin (Drug)
Letrozole +/- goserelin, OSI-906, erlotinib (Arm II)
Patients receive oral letrozole and subcutaneous goserelin (the latter for pre-menopausal women only) and oral IGF-1R inhibitor OSI-906 as in arm I. Patients also receive oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: letrozole (Drug)
结局指标
主要结局
Time to progression
时间窗: from study entry to date of progressive disease
Duration from study enrollment to date of progressive disease (PD) as measured by Response Evaluation in Solid Tumors (RECIST) criteria v. 1.1: measurable lesions: PD is \> 20% increase in the sum of the longest diameter of target lesions or appearance of new lesions
次要结局
- Response(every 12 weeks to progression)
- Safety profile of OSI-906 and letrozole +/ goserelin, with and without erlotinib(at 4 weeks)
- Circulating C-peptide, IGF-1(At baseline and on day 1 of each 28-day cycle)
- Correlation of IGF-IR, EGFR, HER2, Y1316 and Y1131 pIGF-1R, PTEN, S473 pAkt, pMAPK, S118 (MAPK site), and S167 (Akt and S6 site) pER expression with time to progression and molecular classification(On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgery)
- Mutation analysis of PI3K (E542K, E545K, H1047R)(On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgery)
研究者
Ingrid Mayer, MD
Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist
Vanderbilt-Ingram Cancer Center