A Phase Ib Study Evaluating the Safety and Tolerability of Durvalumab (MEDI4736) (Anti-PDL1) in Combination With Eribulin in Patients With HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian Cancer
Overview
- Phase
- Phase 1
- Intervention
- Durvalumab
- Conditions
- HER2-Negative Metastatic Breast Cancer
- Sponsor
- Amy Tiersten
- Enrollment
- 9
- Locations
- 1
- Primary Endpoint
- The dose-limiting toxicity (DLT) rate
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This study will evaluate the recommended Phase 2 combination dose (RP2D) of eribulin with durvalumab.
Detailed Description
STUDY SUMMARY Study Duration: Accrual will take place over the course of 16 months. Patients will be treated until unacceptable toxicity or disease progression (expected on average for 6 months) and then followed for one year thereafter. Objectives: Phase I: To determine the the recommended phase II dose of eribulin in combination with Durvalumab This study will evaluate the recommended Phase 2 combination dose (RP2D) of eribulin with durvalumab. If two or more out of 6 patients experience a dose limiting toxicity (DLT) at dose level I or II, the dose level below that level will be considered the RP2D. If all 3 patients enter dose level-I and experience DLT, the study will be terminated. If the highest level has been reached and \< 33% of patients have experienced DLT, that will be considered the RP2D.
Investigators
Amy Tiersten
Professor
Icahn School of Medicine at Mount Sinai
Eligibility Criteria
Inclusion Criteria
- •Written informed consent and HIPAA authorization obtained from the subject and documented according to local regulatory requirements prior to beginning any protocol-specific procedures, including screening procedures
- •The subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations, including all follow-up
- •The subject is medically fit for protocol therapy and competent to give informed consent
- •The subject must have a performance status of 0-1 as determined by criteria set forward by ECOG
- •Subjects with histologically confirmed stage IV any hormone receptor (HR) status/HER2 negative breast cancer or advanced/recurrent epithelial ovarian cancer
- •HR positive, HER2 negative breast cancer: patients must have received at least one line of therapy for metastatic disease prior to enrollment, including hormonal therapy and a CDK4/6 inhibitor
- •HR negative, HER2 negative breast cancer: patients must have received at least one prior line of chemotherapy for metastatic disease
- •Recurrent, "platinum-sensitive" epithelial ovarian cancer: patients must have received at least two lines of platinum-based chemotherapy prior to enrollment, with at least one of these lines of platinum-based chemotherapy in the recurrent setting
- •Recurrent, "platinum-resistant" (recurrence within 6 months of a platinum-containing chemotherapy regimen) epithelial ovarian cancer: patients must have received at least one line of platinum-based chemotherapy prior to enrollment
- •There is pathologic tissue confirming of metastatic breast or ovarian cancer
Exclusion Criteria
- •Prior treatment with any investigational drug as part of a clinical trial within 28 days prior to study drug administration
- •Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- •The subject has been treated previously with any anti-PD1/PDL1 therapy, including durvalumab
- •The subject has been previously treated with eribulin
- •The subject has received a prior anti-cancer therapy (chemotherapy, targeted small molecule therapy, endocrine therapy, immunotherapy, biologic therapy, tumor embolization, monoclonal antibodies) within 14 days prior to study Day 1
- •Any concurrent anti-cancer therapy other than denosumab, bisphosphonates, or hormonal therapy for non-cancer related conditions
- •The subject has received radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days of the first dose of study drug
- •Major surgical procedure within 28 days prior to the first dose of study drug (local surgery or isolated lesions for palliative intent is acceptable)
- •Any unresolved toxicity NCI CTCAE Grade \>2 from previous anticancer therapy with the exception of alopecia, vitiligo, and lab values which meet inclusion criteria
- •Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study as per consultation with the study physician. These patients will require active and continuous monitoring of this toxicity and if any worsening is observed or identified, study drugs will be permanently discontinued immediately
Arms & Interventions
Her2-negative Metastatic Breast Ca and Recurrent Ovarian Ca
Durvalumab and Eribulin in Her2-negative Metastatic Breast Cancer and Recurrent Ovarian cancer
Intervention: Durvalumab
Her2-negative Metastatic Breast Ca and Recurrent Ovarian Ca
Durvalumab and Eribulin in Her2-negative Metastatic Breast Cancer and Recurrent Ovarian cancer
Intervention: Eribulin
Outcomes
Primary Outcomes
The dose-limiting toxicity (DLT) rate
Time Frame: 42 days
A DLT is defined as a ≥ Grade 3 or 4 study drug-related adverse event (using NCI CTCAE Version 4.03) that occurs during the DLT evaluation period. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded from this definition.
Secondary Outcomes
- Progression free survival (PFS)(16 months)
- Number of Adverse events(6 months)
- Overall survival (OS)(6 months)
- Objective response rate (ORR)(6 months)
- ECOG performance status(6 months)