A Study to Compare the Efficacy of Venetoclax Plus Fulvestrant Versus Fulvestrant in Women with Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer who Experienced Disease Recurrence or Progression During or after CDK4/6Inhibitor Therapy
- Conditions
- Estrogen receptor-positive (ER+)/human epidermal growth factor receptor (HER2)-negative locally advanced or metastatic breast cancer (MBC)MedDRA version: 23.0Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-005118-74-DE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 105
- Female and >= 18 years of age
- Histological or cytological confirmation of ER+ invasive carcinoma of the breast with documented HER2-negative as per ASCO/CAP criteria status. Patients who were originally diagnosed with HER2-positive breast cancer that converted to HER2-negative MBC are not eligible to take part in this study. Evaluable sample for B-cell lymphoma 2 (BCL-2) immunohistochemistry value at time of screening
- Evidence of metastatic or locally advanced disease not amenable to surgical or local therapy with curative intent
- Be either postmenopausal
- OR pre- or perimenopausal and amenable to being treated with the luteinizing hormone-releasing hormone (LHRH) agonist goserelin
- Patients must not have received more than two prior lines of hormonal therapy in the locally advanced or metastatic setting. In addition, at least one line of treatment must be a CDK4/6i and patients must have experienced disease recurrence or progression during or after CDK4/6i therapy, which must have been administered for a minimum of 8 weeks prior to progression
- Patients for whom endocrine therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at the time of entry into the study, as per national or local treatment guidelines
- Women of childbearing potential must have a negative serum pregnancy test result at screening, within 14 days prior to the first study drug administration
- For women of childbearing potential: agreement to remain abstinent or use non-hormonal contraceptive methods with a failure rate of < 1% per year during the treatment period and for up to 2 years after the last dose of study drug (or based on the local prescribing information for (fulvestrant). Women must refrain from donating eggs during this same period
- Willing to provide tumor biopsy sample
- Have at least one measurable lesion via RECIST v1.1
- Have an Eastern Cooperative Oncology Group Performance Score of 0-1
- Have adequate organ and marrow function
- Have adequate blood coagulation
- Have a life expectancy > 3 months
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 105
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
- Prior treatment with fulvestrant or other selective estrogen receptor degraders, venetoclax, or any investigational agent whose mechanism of action is to inhibit BCL-2
- Pregnant, lactating, or intending to become pregnant during the study
- Known untreated or active central nervous system metastases
- Prior chemotherapy in the locally advanced or metastatic setting regardless of the duration of the treatment
- Any anti-cancer therapy received within 21 days of the first dose of study drug, including chemotherapy, radiotherapy (except palliative intent in non-target lesion), hormonal therapy, immunotherapy, antineoplastic vaccines, or other investigational therapy
- Concurrent radiotherapy to any site or prior radiotherapy within 21 days of Cycle 1 Day 1 or previous radiotherapy to the target lesion sites or prior radiotherapy to > 25% of bone marrow
- Current severe, uncontrolled, systemic disease
- Any major surgery within 28 days of the first dose of study drug or anticipation of the need for major surgery during the course of study treatment
- Administration of the following agents within 7 days prior to the first dose of study drug: - Steroid therapy for anti-neoplastic intent, - Strong CYP3A inhibitors or moderate CYP3A inhibitors, - Strong CYP3A inducers or moderate CYP3A inducers
- Consumption of one or more of the following within 3 days prior to the first dose of study drug: Grapefruit or grapefruit products; Seville oranges including marmalade containing Seville oranges; Star fruit (carambola)
- Need for current chronic corticosteroid therapy
- Known infection with HIV or human T-cell leukemia virus 1
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to Cycle 1 Day 1
- Positive test results for hepatitis B core antibody (HBcAb) or hepatitis C virus (HCV) antibody at screening
- Active HCV infection, defined as having a positive HCV antibody test at screening
- History of other malignancies within the past 5 years except for treated skin basal cell carcinoma, squamous cell carcinoma, non-malignant melanoma <= 1.0 mm without ulceration, localized thyroid cancer, or cervical carcinoma in-situ
- Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study
- Cardiopulmonary dysfunction
- Other medical or psychiatric conditions that, in the opinion of the investigatory, may interfere with the patient’s participation in the study
- Inability or unwillingness to swallow pills or receive intra muscular injections
- History of malabsorption syndrome or other condition that would interfere with enteral absorption
- History of inflammatory bowel disease or active bowel inflammation
- Concurrent hormone replacement therapy
- Inability to comply with study and follow-up procedures
- Known hypersensitivity to any of the study medications or to any of the excipients
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