This is an open label multicenter, Phase IB/II Study of Abemaciclib in Combination with Bicalutamide for Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer
Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
If a patient declines to participate in any voluntary exploratory research and/or genetic component of the study, there will be no penalty or loss of benefit to the patient and he/she will not be excluded from other aspects of the study
Women aged at least 18 years
The patient has a biopsy-confirmed diagnosis of recurrent, unresectable, locally advanced, or metastatic HER2neu-negative breast cancer (including bone-only metastatic disease) o The patient must have had biopsy confirmation of a metastatic site (with appropriate ER/PR/HER2neu IHC staining)
Any investigational agents or study drugs from a previous clinical study within 28 days of the first dose of study treatment
Any other chemotherapy, immunotherapy or anticancer agents within 21 days of the first dose of study treatment
Any prior exposure to anti-androgen therapy (bicalutamide, abiraterone, and/or enzalutamide)
Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
Single group
Abemaciclib
Drug100 mg orally twice daily, day 1 to 28. If no toxicity in cycle 1 for the first 3 patients, increase dose to 150mg orally twice daily day 1-28 and enroll 3 patients. If excessive toxicity experienced at 100mg orally twice daily dose, decrease dose to 50mg orally twice daily day 1-28.
Bicalutamide
Drug150 mg orally daily, day 1 to 28.
The Dose-Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)
For the Phase 1 portion of the trial Bayesian optimal interval (BOIN) design is being used. a minimum of 3 and a maximum of 12 patients enrolled to determine the dose-limiting toxicity (DLT) and will be the recommended phase II dose (RP2D). • A DLT will be defined as: * Grade 3 or 4 non-hematologic toxicity * Grade 3 neutropenia lasting greater than 21 days * Grade 3 or 4 neutropenia with neutropenic fever * Grade 4 hematologic toxicity events experienced within the first 4 weeks (1 cycle) of study treatment. These will be assessed via National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v.5.0 toxicity criteria. The DLT period will be the first cycle (28 days) of therapy.
Frequency of Adverse Events (AE)
The frequency and percentage of AE associated with abemaciclib in combination with bicalutamide by the type, severity (as graded by the NCI CTCAE v.5.0), and relationship to study medications.
Disease Control Rate (DCR)
Disease Control Rate (DCR) is defined as the percentage of patients whose cancer shrinks or remains stable over the duration of the study. This will be measured as the sum of complete response (CR), partial response (PR), and stable disease (SD) for greater than or equal to 24 weeks. CR: Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions. PD: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
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