A Study of Taselisib + Fulvestrant Versus Placebo + Fulvestrant in Participants With Advanced or Metastatic Breast Cancer Who Have Disease Recurrence or Progression During or After Aromatase Inhibitor Therapy

• Status: Completed
• Trial end date: 2021-07-08
• Target enrollment: 0
• Participant gender: Female

Summary

This international, multicenter, randomized, double-blinded, placebo-controlled study is designed to compare the efficacy and safety of taselisib + fulvestrant with that of placebo + fulvestrant in postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative, oncogene that encodes for phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA)-mutant, unresectable, locally advanced or metastatic breast cancer after recurrence or progression during or after an aromatase inhibitor (AI) therapy. There will be a 2:1 randomization to the taselisib arm versus the placebo arm. Enrollment will be enriched for participants with PIK3CA mutant tumors via central testing. The anticipated duration of the study is approximately 3.5 years.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Aromatase Inhibitors; Estradiol; Fulvestrant

Criteria

Inclusion Criteria:

• Postmenopausal women with histologically or cytologically confirmed locally advanced or metastatic estrogen receptor (ER) positive breast cancer

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Participants for whom endocrine therapy (example [e.g.], fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study

• Radiologic/objective evidence of recurrence or progression to the most recent systemic therapy for breast cancer

• Radiologic/objective evidence of breast cancer recurrence or progression while on or within 12 months of the end of adjuvant treatment with an aromatase inhibitor (AI), or progression while on or within 1 month of the end of prior AI treatment for locally advanced or metastatic breast cancer

• Measurable disease via Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) or non-measurable, evaluable disease with at least one evaluable bone lesion via RECIST v1.1

• Consent to provide a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block (preferred) or a minimum of 20 (25 preferred) freshly cut unstained tumor slides from the most recently collected, available tumor tissue for oncogene that encodes for phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA)-mutation testing

• A valid cobas PIK3CA mutation result by central testing is required

• Adequate hematologic and end-organ function within 28 days prior to treatment initiation

Exclusion Criteria:

• Human epidermal growth factor receptor 2 (HER2)-positive disease by local laboratory testing (immunohistochemistry 3 positive [IHC 3+] staining or in situ hybridization positive)

• Prior treatment with fulvestrant

• Prior treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor, mammalian target of rapamycin (mTOR) inhibitor (e.g. everolimus), or protein kinase B (AKT) inhibitor

• Prior anti-cancer therapy within 2 weeks prior to Day 1 of Cycle 1

• Prior radiation therapy within 2 weeks prior to Day 1 of Cycle 1

• All acute treatment-related toxicity must have resolved to Grade less than or equal to (
• Prior treatment with greater than (>) 1 cytotoxic chemotherapy regimen for metastatic breast cancer

• Concurrent hormone replacement therapy

• Known untreated or active central nervous system (CNS) metastases

• Type 1 or Type 2 diabetes mellitus requiring anti-hyperglycemic medications

• History of inflammatory bowel disease or active bowel inflammation

• Clinically significant cardiac or pulmonary dysfunction

• Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B or C virus