A Study Evaluating the Efficacy and Safety of GDC-0077 Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Patients with PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer.

Phase 1

Active, not recruiting

• Conditions: Breast cancer; MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002455-42-IT
• Lead Sponsor: F. HOFFMANN - LA ROCHE LTD.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-25
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

Signed Informed Consent Form
- Women or men ¿ 18 years of age at time of signing Informed Consent Form
- If female, patients must meet at least one of the following definitions:
Postmenopausal, as defined by at least one of the following criteria:
– Age 60 years
– Age 60 years and 12 months of amenorrhea plus follicle-stimulating hormone and plasma estradiol levels within postmenopausal range by local laboratory assessment in the absence of oral contraceptive pills, hormone replacement therapy, or gonadotropin-releasing hormone agonist or
antagonist
– Documented bilateral oophorectomy (14 days prior to first treatment on
Day 1 of Cycle 1 and recovery to baseline)
Premenopausal or perimenopausal (i.e., not meeting the criteria for postmenopausal) and meeting the following criterion:
– Treatment with luteinizing hormone¿releasing hormone (LHRH) agonist therapy (e.g., goserelin or leuprolide) beginning at least 2 weeks prior to Day 1 of Cycle 1 and continuing for the duration of study treatment
If male, recommendation of treatment with LHRH agonist therapy (e.g., goserelin or leuprolide) beginning at least 2 weeks prior to Day 1 of Cycle 1 and continuing for the duration of study treatment
-Histologically or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent - Documented ER-positive and/or progesterone receptor¿positive tumor according to American Society of Clinical Oncology/College of American Pathologists
(ASCO/CAP) guidelines, defined as ¿ 1% of tumor cells stained positive based on
the most recent tumor biopsy and assessed locally
- Documented HER2-negative tumor according to ASCO/CAP guidelines, defined as a HER2 immunohistochemistry (IHC) score of 0 or 1¿, or an IHC score of 2¿ accompanied by a negative fluorescence, chromogenic, or silver in situ hybridization
test indicating the absence of HER2 gene amplification, or a HER2/CEP17 ratio of 2.0 based on the most recent tumor biopsy and assessed locally
- Confirmation of biomarker eligibility: valid results from either central testing of blood
or local testing of blood or tumor tissue documenting PIK3CA-mutant tumor status
-Consent to provide fresh (preferred) or archival tumor tissue specimen. It is preferred that the specimen be from the most recently collected and available tumor tissue, and whenever possible, from a metastatic site of disease. See the laboratory manual for specimen requirements.
- Patients must have progressed during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
- Measurable disease per RECIST v1.1
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion Criteria

- Metaplastic breast cancer
-Any history of leptomeningeal disease or carcinomatous meningitis
-Any prior systemic therapy for metastatic breast cancer
Prior treatment with fulvestrant or any selective estrogen-receptor degrader
- Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose
mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
- Appropriate for treatment with cytotoxic chemotherapy at time of entry into the
study, as per national or local treatment guidelines (e.g., patients with visceral crisis)
- Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or
any history of Type 1 diabetes
- Inability or unwillingness to swallow pills or receive intramuscular injections
- Malabsorption syndrome or other condition that would interfere with
enteral absorption
- Known and untreated, or active CNS metastases
- Clinically significant and active liver disease, including severe liver impairment (Child-Pugh Class B/C), viral or other hepatitis, current alcohol abuse, or cirrhosis

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified