A phase III, double-blind, placebo-controlled, randomized study of Taselisib plus Fulvestrant versus placebo plus Fulvestrant in postmenopausal women with estrogen receptor-positive and her2-negative locally advanced or metastatic breast cancer who have disease recurrence or progression during or after aromatase inhibitor therapy

• Register: RPEC
• Last refreshed on: 4 September 2023
• Main ID: PER-037-15
• Date of registration: 16/09/2015
• Prospective Registration: Yes
• Primary sponsor: F. HOFFMANN-LA ROCHE LTD.,
• Public title: A phase III, double-blind, placebo-controlled, randomized study of Taselisib plus Fulvestrant versus placebo plus Fulvestrant in postmenopausal women with estrogen receptor-positive and her2-negative locally advanced or metastatic breast cancer who have disease recurrence or progression during or after aromatase inhibitor therapy
• Scientific title: A phase III, double-blind, placebo-controlled, randomized study of Taselisib plus Fulvestrant versus placebo plus Fulvestrant in postmenopausal women with estrogen receptor-positive and her2-negative locally advanced or metastatic breast cancer who have disease recurrence or progression during or after aromatase inhibitor therapy
• Date of first enrolment: 26/03/2016
• Target sample size: 12
• Recruitment status: Pending
• URL: https://www.ins.gob.pe/ensayosclinicos/rpec/recuperarECPBNuevoEN.asp?numec=037-15
• Study type: Interventional
• Study design: Study GO29058 is a Phase III, randomized, multicenter, international, double-blind, placebo-controlled clinical study designed to compare the efficacy, as measured by PFS, and safety of fulvestrant + taselisib with that of fulvestrant + placebo after recurrence or progression following treatment with an AI for patients with ER+, HER2-negative, PIK3CA-mutant, unresectable, locally advanced or MBC. PIK3CA-mutation status in all patients will be assessed by a central laboratory using the cobas® PIK3CA Mutation Test. In order to explore efficacy and differential benefit-risk in patients without a detectable PIK3CA mutation, a number of patients (n = 120 patients) belonging to this category will be enrolled.; Patients (n = 600) will be randomized in a 2:1 ratio to either fulvestrant + taselisib or fulvestrant + placebo (see Figure 1). Patients whose tumors contain a PIK3CA-mutation (n = 480) and patients whose tumors do not contain a detectable PIK3CA-mutation (n = 120
• Phase: III

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Costa Rica, Croatia, Czech Republic, Dominican Republic, El Salvador, Estonia, Finland, France, Germany, Greece, Guatemala, Hungary, Israel, Italy, Japan, Korea South, Latovia, Mexico, Netherlands, Panama, Paraguar, Poland, Portugal, Romania, Russian Federation, Slovakia, Slovenia, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kindgdom, United States

Contacts

• Name: Roberto Navarro Carrasco
• Affiliation: ROCHE FARMA (PERU) S.A.

• Name: Roberto Navarro Carrasco
• Affiliation: ROCHE FARMA (PERU) S.A.

Key inclusion & exclusion criteria

Inclusion criteria: • Women with histologically or cytologically confirmed invasive, ER+ breast cancer:metastatic or inoperable (not amenable to resection or other local therapy with curative intent) locally advanced breast cancer. • Patients for whom endocrine therapy (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 AI, or progression while on or within 1 month of the end of prior AI treatment for locally advanced or MBC. The AI (letrozole, anastrozole, or exemestane) does not have to be the most recent treatment before randomization. • Measurable disease via RECIST v1.1 or non-measurable, evaluable disease with at least one evaluable bone lesion via RECIST v1.1. Bone lesions that have been irradiated are not evaluable. • Able and willing to provide written informed consent and to comply with the study protocol. • Age ≥ 18 years. • ECOG of 0 or 1. • Postmenopausal status. • Consent to provide a formalin-fixed paraffin. • A valid cobas PIK3CA mutation result. • Adequate hematologic and end-organ function. • Fasting glucose ≤ 125 mg/dL (6.94 mmol/L)
Exclusion criteria: • HER2-positive • Prior treatment with fulvestrant. • Prior treatment with a PI3K, mTOR, or AKT inhibitor. • Prior anti-cancer therapy within 2 weeks prior to Cycle 1 Day 1. • Prior radiation therapy within 2 weeks prior to Cycle 1 Day 1. • All acute treatment-related toxicity must have resolved to Grade ≤ 1 or be deemed stable. • Prior treatment with > 1 cytotoxic chemotherapy regimen for MBC. • Symptomatic hypercalcemia requiring continued use of bisphosphonate or denosumab therapy. • Concurrent hormone replacement therapy. • Known untreated or active CNS metastases. •History of other malignancy. • Type 1 or Type 2 diabetes mellitus requiring medications. • Clinically significant cardiac or pulmonary dysfunction • Current dyspnea at rest or any requirement for supplemental oxygen therapy to perform activities of daily living. • History of malabsorption syndrome or other condition that would interfere with enteral absorption. • Inability or unwillingness to swallow pills or receive intramuscular injections. • Clinically significant history of liver disease. • History of inflammatory bowel disease. • Active bowel inflammation. • Immunocompromised status. • Pregnancy, lactation, or breastfeeding. • Current severe, uncontrolled systemic disease. • Major surgical procedure within 28 days prior to Cycle 1 Day 1 or anticipation of the need for major surgery during the course of study treatment • Inability to comply with study. • Inability to understand EORTC QLQ-C30, QLQ-BR23, and the EQ-5D questionnaires are available.

Age minimum: 18
Age maximum: 80
Gender: Female

Health Condition(s) or Problem(s) studied

C50

Malignant neoplasm of breast

-C50 Malignant neoplasm of breast
Malignant neoplasm of breast

Intervention(s)

The taselisib tablet is a white to off-white, film coated, immediate release formulation of 2-mg strength. The taselisib 4-mg dose will be taken orally (PO) once a day (QD). Taselisib is formulated as 2-mg tablets, so patients will take two 2-mg tablets daily to receive a 4-mg dose. Patients should take the taselisib dose at the same approximate time each day without regard to the timing of administration of food. If a dose is missed (not taken within 6 hours after the scheduled dosing time), the patient should resume dosing with the next scheduled dose. Missed or vomited doses will not be made up.
The taselisib placebo (corresponding to a 4-mg dose) will be two tablets taken PO QD. The taselisib placebo should be taken at the same approximate time each day without regard to the timing of administration of food. If a dose is missed (not taken within 6 hours after the scheduled dosing time), the patient should resume dosing with the next scheduled dose. Missed or vomited doses will not be made up.

Fulvestrant 500 mg will be administered at site (before administration of taselisib or placebo) as two intramuscular injections of 250 mg each on Cycle 1 Days 1 and 15 and Day 1 of each subsequent 28-day cycle.

Source(s) of Monetary Support

Industria Farmaceutica

Ethics review

Status: Approved
Approval date: 09/06/2015
Contact:

[e-mail] - [e-mail]

Universidad San Martin de Porres

999098514

[e-mail] - [e-mail]

Status: Approved
Approval date: 12/06/2015
Contact:

[e-mail]

Instituto Nacional de Enfermedades Neoplasicas

7106099-3001

[e-mail]

Status: Approved
Approval date: 17/12/2015
Contact:

[e-mail]

Instituto Regional de Enfermedades Neoplasicas - IREN NORTE

948041588

[e-mail]

Results

• Results available: Yes
• Date Completed: 28/08/2020