A multi-part, clinical study testing the safety and effectiveness of cobimetinib in combination with paclitaxel as initial treatment for patients with triple-negative (HER2 negative, Estrogen receptor negative, and Progesterone receptor negative) breast cancer that has spread.
- Conditions
- Patients with metastatic or locally advanced, triple-negative adenocarcinoma of the breast that have not received prior systemic therapy for metastatic breast cancer.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-002230-32-ES
- Lead Sponsor
- F. Hoffman-La Roche Ltd., realizado en España por Roche Farma S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 112
?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 < 1% per year during the treatment period and for at least 6 months after the last dose of study drug
? The determination of TNBC status should, whenever possible, utilize tissue from a metastatic or recurrent lesion and where more than one biopsy source is available, priority should be given to the most recent
sample.
? 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.
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 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
?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 (
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method