Solid tumors, Breast cancer Cancer Malignant neoplasm of breast
Conditions
Interventions
Current interventions as of 20/07/2022:
The study is an open-label design and the treatments include:
Inavolisib - 6 mg/9 mg taken orally every day and potentially on an intermittent weekly schedule o
Sponsors
Genentech, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 20/07/2022: 1. Signed Informed Consent Form 2. Aged over 18 years and over 3. Evaluable or measurable disease per RECIST, v1.1 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 5. Life expectancy of >12 weeks 6. Adequate hematologic and organ function within 14 days prior to initiation of study treatment, defined by the following: 6.1. Absolute neutrophil count 1500/µl 6.2. Hemoglobin =9 g/dl 6.3. Platelet count =100,000/l 6.4. Fasting glucose <126 mg/dL or <7 mmol/l and glycosylated hemoglobin (HbA1C) 5.7% or <39 millimoles per mole (mmol/mol) 6.5. Total bilirubin <1.5 upper limit of normal (ULN) 6.6. Serum albumin =2.5 g/dl or 25 g/l 6.7. AST and ALT =2.5 ULN with the following exception: patients with documented liver metastases may have AST and ALT =5.0 ULN. 6.8. Serum creatinine 1.5 ULN or creatinine clearance =50 ml/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation 6.9. International normalized ratio (INR) <1.5 x upper limit of normal (ULN) and activated partial thromboplastin time (aPTT) <1.5 x ULN 7. 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. 8. Consent to provide a freshly collected pre-treatment blood sample. 9. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a highly effective form of contraceptive method with a failure rate of 1% per year in combination with use of male condom with spermicide (for male partners), unless male sterilization has been confirmed. 10. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive measures, and agreement to refrain from donating sperm. Inclusion Criteria Specific to Patients Enrolling in Part 1, Arm A: Histologically documented, locally advanced, recurrent, or metastatic, incurable solid tumor malignancy that has progressed after available standard systemic therapies; or for whom standard therapy has proven to be ineffective or intolerable; or for whom a clinical trial of an investigational agent is a recognized standard of care. If there are other available SOC therapies, these will be discussed with the patient and documented before informed consent is obtained. Inclusion Criteria Specific to Patients Enrolling in Part 2, Arm A Expansion Cohorts: 1. Histologically documented, locally advanced, recurrent, or metastatic, incurable solid tumor malignancy with a known PIK3CA mutation that has progressed after at least one available standard systemic therapy in the metastatic setting. – Cohort 1 (HNSCC): Histologically or cytologically confirmed recurrent and/or metastatic HNSCC that has been previously treated with systemic therapy in the recurrent and/or metastatic setting, which may include immunotherapy and/or chemotherapy with or without cetuximab. – Cohort 2 (ovarian cancer): Persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal tumors that have been previously treated with up to 4 prior regimens in the recurrent and/or metastatic setting, being at least one platinum-based. Patients may have received bevacizumab and/or poly-ADP ribose polymerase (PARP) inhibitors. – Cohort 3 (TNBC): Histologically or cytologically confirmed adenocarcinoma of the breast that is locall
Exclusion criteria
Exclusion criteria: 1. Metaplastic breast cancer 2. Any history of leptomeningeal disease 3. Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes 4. Inability or unwillingness to swallow pills 5. Malabsorption syndrome or other condition that would interfere with enteral absorption 6. Known and untreated, or active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). 7. Uncontrolled pleural effusion or ascites requiring recurrent drainage procedures twice per month or more frequently 8. Any active infection that, in the opinion of the investigator, could impact patient safety; or, serious infection requiring IV antibiotics within 7 days prior to Day 1 of Cycle 1 9. Any concurrent ocular or intraocular condition (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator or study ophthalmologist, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition 10. Active inflammatory (e.g., uveitis or vitritis) or infectious (e.g., conjunctivitis, keratitis, scleritis, or endophthalmitis) conditions in either eye or history of idiopathic or autoimmuneassociated uveitis in either eye 11. Patients requiring any daily supplemental oxygen 12. History of or active inflammatory disease (e.g., Crohn’s disease or ulcerative colitis), or any active bowel inflammation (including diverticulitis). Patients currently receiving immunosuppressants (e.g., sulfasalazines) are considered to have active disease; therefore, they are ineligible. 13. Symptomatic hypercalcemia requiring continued use of bisphosphonate or denosumab therapy 14. Clinically significant history of liver disease, including severe liver impairment (Child-Pugh Class B/C), viral or other hepatitis, current alcohol abuse, or cirrhosis 15. Known HIV infection 16. Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the patients at high risk from treatment complications 17. Significant traumatic injury or major surgical procedure within 4 weeks prior to initiation of study treatment 18. Radiation therapy (other than palliative radiation to bony metastases) as cancer therapy within 4 weeks prior to initiation of study treatment 19. Palliative radiation to bony metastases within 2 weeks prior to initiation of study treatment 20. Unresolved toxicity from prior therapy, except for the following: Alopecia Grade 1 and peripheral neuropathy 21. Inability to comply with study and follow-up procedures 22. History of other malignancy within 5 years prior to screening, with the exception of patients with a negligible risk of metastasis or death and/or treated with expected curative outcome (such as appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer) 23. History of or active ventricular dysrhythmias or congestive heart failure requiring medication or coronary heart disease that is symptomatic 24. Clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia) 25.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Objectives: 1. Incidence and nature of dose-limiting toxicities (Part 1 only) measured using adverse events (graded by NCI CTCAE v5.0) recorded within the first 28 days (cycle 1) of study treatment 2. Incidence, type, and severity of adverse events including serious adverse events graded by NCI CTCAE v5.0 recorded throughout the study 3. Targeted vital signs measured using standard techniques assessed by site staff at baseline and weekly/monthly during study treatment 4. Targeted clinical laboratory test results measured using standard hospital laboratory analyses at baseline and taken every week/cycle, including ECGs, recorded by taken by site staff at baseline and every cycle during study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 20/07/2022: Pharmacokinetic Objective (Secondary Objective): Plasma concentration of inavolisib administered in combination with paclitaxel (Arm A) measured by a bioanalytical laboratory at Cycles 1-3. The following PK parameters will be determined as appropriate: 1. Area under the concentration-time curve (AUC) 2. Maximum plasma concentration (Cmax) 3. Minimum plasma concentration (Cmin) 4. Additional plasma PK parameters as warranted Activity/Efficacy Objectives (Secondary Objectives): Preliminary assessment of the anti-tumor activity of: 1. Inavolisib administered in combination with paclitaxel in patients with locally advanced or metastatic PIK3CA-mutated solid tumors (*Part 2 Arm A) The corresponding endpoints are as follows: 1. Objective response rate (ORR) defined as a complete recovery (CR) or partial recovery (PR) on two consecutive occasions =4 weeks apart, as determined by the investigator through use of RECIST v1.1 every 8(*) weeks during the study treatment 2. Best overall response (BOR) defined as the proportion of patients with a CR or PR, as determined by the investigator through use of RECIST v1.1 every 8(*) weeks during study treatment 3. Duration of response (DOR) defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator through the use of RECIST v1.1, or death, whichever occurs first, every 8(*) weeks during study treatment 4. Clinical benefit rate (CBR) defined as the percentage of patients achieving confirmed RECIST v1.1 defined CR, PR, or stable disease (SD; non-complete response/non-progressive disease for patients with non-measurable disease at baseline) =24 weeks, as determined by the investigator through use of RECIST v1.1 every 8(*) weeks during study treatment 5. Progression-free survival (PFS) defined as the time from the first study treatment (Day 1) to the first occurrence of disease progression, as determined by | — |
Countries
Brazil, Canada, Denmark, France, Korea, South, Spain, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed