Patients with metastatic or locally advanced, triple-negative adenocarcinoma of the breast that have not received prior systemic therapy for metastatic breast cancer.
Conditions
Interventions
Product Name: Cobimetinib (GDC-0973)
Product Code: RO5514041/F04
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cobimetinib (GDC-0973)
Sponsors
F. Hoffman-La Roche Ltd., realizado en España por Roche Farma S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ?Signed Informed Consent Form ?Women and men, age ? 18 years ?Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 ?Histologically confirmed ER negative, PR negative, and HER2-negative adenocarcinoma of the breast, with measurable metastatic or locally recurrent disease ?Locally recurrent disease must not be amenable to resection with curative intent. ?Measurable disease, according to RECIST, v1.1 (see Appendix 4) ?Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to first dose of study drug treatment: ?Absolute neutrophil count (ANC) ? 1.5 × 10 exp9/L ?Platelet count ? 100 × 10 exp9/L ?Hemoglobin ? 9 g/dL ?Albumin ? 2.5 g/dL ?Bilirubin ? 1.5 × the upper limit of normal (ULN) ?Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase ? 3 × ULN, with the following exceptions: -Patients with documented liver metastases: AST and/or ALT ? 5 × ULN -Patients with documented liver or bone metastases: alkaline phosphatase ? 5 × ULN ?Serum creatinine ? 1.5 × ULN or creatinine clearance (CrCl) ? 40 mL/min on the basis of measured CrCl from a 24-hour urine collection or Cockroft-Gault glomerular filtration rate estimation: (140-age) x (weight in kg) x (0.85 if female) 72 x (serum creatinine in mg/dL) ?Ability and capacity to comply with the study and follow-up procedure ?For female patients (and female partners of male patients) who are not postmenopausal (? 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: ?Known HER2 positive, ER positive, or PR positive breast cancer by local laboratory assessment (if more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the Medical Monitor to establish eligibility of the patient). ?HER2 positivity is defined as one of the following: IHC 3 positive or in situ hybridization (ISH) positive ?ER and PR positivity is defined positive for ER or PR if a ?nding of ?1% of tumor cell nuclei are immunoreactive ?Patients who have not had HER2, ER, or PR testing, and thus, the HER2, ER, and PR status of the breast adenocarcinoma is unknown, are not eligible. ?Any prior chemotherapy, hormonal, or targeted therapy, for inoperable locally advanced or mTNBC ?Prior chemotherapy (including taxanes) and/or radiation in the neoadjuvant or adjuvant setting is allowable if treatment occurred ? 6 mos prior to initiation of study treatment (Cycle 1 Day1) ?Any systemic anti-cancer therapy within 3 weeks prior to Cycle 1, Day 1 ?Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1 ?Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1, Day 1, or anticipation of need for major surgical procedure during the course of the study ?Prior therapy with bevacizumab, sorafenib, sunitinib, or other putative vascular endothelial growth factor pathway?targeted therapy following diagnosis of breast cancer ?Prior exposure to experimental treatment targeting Raf, MEK, or the MAPK pathway ?Previous therapy with Akt, PI3K, and/or mTOR inhibitors ?Prior therapy with trastuzumab ?Grade ? 2 peripheral neuropathy ?Brain metastases (symptomatic or non-symptomatic) that have not been treated previously, are progressive, or require any type of therapy (e.g. radiation,surgery or steroids) to control symptoms from brain metastases within 60 days prior to first study treatment dose ?History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment / central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration ?Patients will be excluded if they currently have the following risk factors for RVO: -Uncontrolled glaucoma with intra-ocular pressures ? 21mmHg -Serum cholesterol ? Grade 2 -Hypertriglyceridemia ? Grade 2 -Hyperglycemia (fasting) ? Grade 2 -Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower. -The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment: -St. John?s wort or hyperforin (potent CYP3A4 enzyme inducer) -Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor) -Pregnancy (positive serum pregnancy test) or lactation -Uncontrolled serious medical or psychiatric illness -Active infection requiring intravenous (IV) antibiotics on Cycle 1 Day 1 ?QTc interval at screening > 480 msec (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the clinical benefit of cobimetinib + paclitaxel relative to placebo + paclitaxel, as measured by investigator-assessed PFS in patients with locally advanced or metastatic TNBC.;Primary end point(s): The primary efficacy endpoint is PFS, defined as the time from randomization to the first occurrence of disease progression, as determined by investigator per RECIST v1.1, or death on study from any cause, whichever occurs first.;Timepoint(s) of evaluation of this end point: The PFS analysis will be performed after approximately 60 investigator-assessed PFS events (estimated to be approximately 21 months after the first patient is enrolled).; Secondary Objective: -To evaluate the safety and tolerability of cobimetinib administered in combination with paclitaxel in patients with locally advanced or metastatic TNBC. -To determine the overall response rate (ORR) and duration of response of cobimetinib + paclitaxel and placebo + paclitaxel -To evaluate OS benefit of cobimetinib + paclitaxel and placebo + paclitaxel -To characterize the pharmacokinetics of cobimetinib administered in combination with paclitaxel | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival, defined as the time from randomization to death from any cause, regardless of whether the death occurs during the study or following treatment discontinuation. For patients who have not died, OS will be censored at the date of last contact. OS will be analyzed similarly to the primary endpoint.;Timepoint(s) of evaluation of this end point: To be done at time of primary analysis | — |
Countries
Australia, Belgium, Czech Republic, France, Korea, Republic of, Latvia, Lithuania, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed