Breast cancer MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: GDC-0077
Product Code: RO7113755/F08-02, RO7113755/F14-02
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not Available
Current Sponsor code: RO7113755
Other descriptive nam
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Women or men >= 18 years of age - Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal - Confirmed diagnosis of HR+/HER2–negative breast cancer - Metastatic or Locally Advanced disease not amenable to curative therapy - Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test) - Consent to provide fresh or archival tumor tissue specimen - Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen - Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1. Evaluable “bone-only” disease is not eligible; "bone-only" disease with at least one measurable, soft-tissue component per RECIST v1.1 may be eligible - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Life expectancy of > 6 months - Adequate hematologic and organ function within 14 days prior to initiation of study treatment - Ability, in the investigator’s judgment, and willingness to comply with all study-related procedures, including completion of patient-reported endpoints - For patients enrolled in China: Current resident of mainland China and must be of Chinese ancestry 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 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
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, with the exception of patients that have received fulvestrant or any selective estrogen receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months - Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway - 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 - Known and untreated, or active CNS metastases. Patients with a history of treated CNS metastases may be eligible - Uncontrolled pleural effusion, pericardial effusion, or ascites - Active inflammatory or infectious conditions in either eye, or history of idiopathic or autoimmune associated uveitis in either eye - Symptomatic active lung disease, or requiring daily supplemental oxygen - History of inflammatory bowel disease or active bowel inflammation - Anti-cancer therapy within 2 weeks before study entry - Investigational drug(s) within 4 weeks before randomization - Prior radiotherapy to >= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation - History of other malignancy within 5 years prior to screening, except for cancers with very low risk of recurrence including, but not limited to, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer - History of or active clinically significant cardiovascular dysfunction - Chronic corticosteroid therapy or immunosuppressants - Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of study treatment - Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of inavolisib plus palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant on the basis of progression-free survival;Secondary Objective: •To evaluate the efficacy of inavolisib plus palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant on the basis of objective response rate; best overall response rate; duration of response; clinical benefit rate; overall survival; and times to deterioration in pain, physical function, role function, and global health status (GHS)/health-related quality of life (HRQoL) •To evaluate the safety of inavolisib plus palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant on the basis of incidence and severity of adverse events, and changes from baseline in: targeted vital signs,clinical laboratory test results, and electrocardiogram (ECG) parameters •To characterize the pharmacokinetics (PK) of inavolisib, palbociclib, and fulvestrant,when administered in combination in this population on the basis of their plasma concentrations •To characterize the PK of inavolisib at additional timepoints in patients enrolled in China;Primary end point(s): 1.Progression-free survival;Timepoint(s) of evaluation of this end point: Up to 6 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective response rate 2. Best overall response rate 3. Duration of response 4. Clinical benefit rate 5. Overall survival 6. Time to deterioration (TTD) in pain 7. TTD in physical function 8. TTD in role function 9. TTD in GHS/HRQoL 10. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) 11. Change from baseline in targeted vital signs 12. Change from baseline in targeted clinical laboratory test results 13. Change from baseline in ECG parameters 14. Plasma concentration of inavolisib at specified timepoints 15. Plasma concentration of inavolisib at additional specified timepoints, in patients enrolled in China 16. Plasma concentration of palbociclib at specified timepoints 17. Plasma concentration of fulvestrant at specified timepoints ;Timepoint(s) of evaluation of this end point: 1-5. Up to 6 years 6-9. Day 1 of Cycle 1, on the planned Day 1 of Cycle 2 and 3 then at the planned Day 1 of every other cycle (i.e., C5, C7, etc.) and at treatment discontinuation. During post-treatment follow-up, PROs collected every 8 weeks during the first 2 years on study, then every 12 weeks 10. Up to 30 days after the final dose of study treatment, or until initiation of another anti-cancer therapy 11-13. From baseline (Day 1 of Cycle 1) to 30 days after the final dose of study treatment 14. Day 1, 8, 15 of Cycle 1; Day 15 of Cycle 2 15. Day 1, 2, 8, 15, 16 of Cycle 1; Day 15 of Cycle 2 16-17. Day 1, 8, 15 of Cycle 1; Day 15 of Cycle 2 | — |
Countries
Australia, Austria, Belgium, Canada, Denmark, France, Germany, Greece, Hong Kong, Hungary, Italy, Korea, Democratic People's Republic of, New Zealand, Poland, Portugal, Russian Federation, Singapore, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed