study of gdc-0941 or gdc-0980 with fulvestrant versus fulvestrant in advanced or metastatic breast cancer in participants resistant to aromatase inhibitor therapy

Conditions: Breast Cancer

Summary: this is a multicenter, international, randomized, double-blinded, placebo-controlled, phase ii trial. participants with advanced breast cancer (abc) or metastatic breast cancer (mbc) who have experienced recurrence or progression of their disease while receiving aromatase inhibitor (ai) therapy or who have relapsed within 6 months after completing adjuvant ai therapy will be enrolled in part i of this study. participants with abc or mbc who have received prior ai therapy and who have pik3ca-mutant tumors will be enrolled in part ii of this study. part i of the study will assess the effect of the addition of gdc-0941 to fulvestrant (arm a) and of gdc-0980 to fulvestrant (arm b) on progression free survival (pfs) compared with fulvestrant + placebo (arm c). part ii of the study will examine the safety and tolerability and to estimate the effect of gdc-0941 in combination with fulvestrant (arm d) on pfs versus fulvestrant + placebo (arm e) in participants who received prior treatment with an ai and whose tumors contain a pik3ca mutation.


Eligibility criteria:
inclusion criteria: * eastern cooperative oncology group (ecog) performance status of 0 or 1 * as per national or local treatment guidelines, endocrine therapy (i.e., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not necessary for participants, at time of entry into the study. * part i: postmenopausal women with locally abc or mbc whose disease relapsed during treatment with (or within 6 months after discontinuation of) an ai in the adjuvant setting or progressed during treatment with an ai in the metastatic setting. * part ii: postmenopausal women with locally abc or mbc whose disease has progressed during or after treatment with an ai. participants who discontinued the ai for toxicity rather than completion of regimen or for disease progression are not eligible * estrogen receptor (er)-positive disease and human epidermal receptor 2 (her2)-negative disease * participants must have measurable disease by response evaluation criteria in solid tumors (recist) version (v) 1.1 or bone-only disease with radiologic scans * adequate hematologic and end-organ function exclusion criteria: * prior treatment with fulvestrant, phosphoinositide 3-kinase (pi3k) inhibitor, or mechanistic target of rapamycin (mtor) inhibitor for abc or mbc * prior anti-cancer therapy or radiotherapy within 2 weeks prior to day 1 of cycle 1 * prior treatment with greater than (\>) one cytotoxic chemotherapy regimens or experienced recurrent or progressive disease on \> two endocrine therapies for mbc * participants requiring anti-hyperglycemic therapy * clinically significant cardiac or pulmonary dysfunction * history of malabsorption syndrome or other condition that would interfere with enteral absorption * clinically significant history of liver disease * active uncontrolled autoimmune disease or active inflammatory disease * immunocompromised status * need for current chronic corticosteroid therapy * pregnancy, lactation, or breastfeeding * current severe, uncontrolled systemic disease * symptomatic hypercalcemia * known untreated or active central nervous system (cns) metastases * history of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, stage i uterine cancer, or patients who have undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to be at low risk for recurrence