Durvalumab and Eribulin in Her2-negative Metastatic Breast Cancer and Recurrent Ovarian Cancer

NCT03430518 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: GCO 17-2320
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the recommended Phase 2 combination dose (RP2D) of eribulin with durvalumab.

Conditions

HER2-Negative Metastatic Breast Cancer; Recurrent Ovarian Cancer

Keywords

Durvalumab (MEDI4736) (Anti-PDL1); Eribulin; Recurrent Ovarian cancer; Her2-negative Metastatic Breast Cancer; Ovarian cancer; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• The dose-limiting toxicity (DLT) rate

  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.

  42 days

Secondary Outcomes (5)

• Number of Adverse events

  6 months

• Objective response rate (ORR)

  6 months

• Progression free survival (PFS)

  16 months

• Overall survival (OS)

  6 months

• ECOG performance status

  6 months

Study Arms (1)

Her2-negative Metastatic Breast Ca and Recurrent Ovarian Ca

EXPERIMENTAL

Durvalumab and Eribulin in Her2-negative Metastatic Breast Cancer and Recurrent Ovarian cancer

Drug: Durvalumab; Drug: Eribulin

Interventions

Durvalumab DRUG

1.12g given IV on day 1 every 21 day cycle

Her2-negative Metastatic Breast Ca and Recurrent Ovarian Ca

Eribulin DRUG

1.1 mg/m2 IV on day 8 of every 21 day cycle in the first 3 patients, then increased to 1.4mg/m2 IV on day 1 and day 8 of every 21 day cycle. If significant toxicity occurs in patients given the 1.1mg/m2 IV dose, then subsequent patients with receive eribulin 0.7mg/m2 IV on day 1 and day 8 of every 21 day cycle.

Her2-negative Metastatic Breast Ca and Recurrent Ovarian Ca

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• All adverse events from prior chemotherapy, radiation, or surgery have either returned to baseline or are \< grade 1 prior to administration of the investigational product
• The subject has a body weight of greater than 30kg
• The subject must have at the time of screening acceptable hematologic, hepatic, and renal function, defined by the following (≤ 28 days prior to registration):
• Absolute neutrophil count \> 1500/mm3
• Hemoglobin \> 10g/dL

You may not qualify if:

• 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)
• 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
• Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with eribulin or durvalumab may be included after consultation with the study physician
• The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression or immunodeficiency
• The subject has a history of allogeneic organ or bone marrow transplantation
• The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a systemic auto-immune/inflammatory disease or other autoimmune disorder, including but not limited to inflammatory bowel disease (Crohn's disease or ulcerative colitis), active diverticulitis, systemic lupus erythematosus, Sarcoidosis, Wegener's granulomatosis, granulomatosis with polyangiitis, pneumonitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis.
• Exceptions: vitiligo, alopecia, autoimmune-related hypothyroidism which is stable on hormone replacement, chronic skin conditions that do not require systemic therapy, celiac disease controlled with diet alone, or any subjects without active disease in the last 5 years if deemed appropriate by the study physician
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exception of inhaled, local injection, or intranasal corticosteroids, systemic steroids at physiological doses (equivalent of ≤ 10mg prednisone daily), and steroid premedication for hypersensitivity reactions (e.g., CT scan premedication)

Sponsors & Collaborators

• Amy Tiersten: lead
• AstraZeneca: collaborator
• Eisai Inc.: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Breast Neoplasms

Interventions

durvalumab; eribulin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Amy Tiersten, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 6, 2018
• First Posted: February 13, 2018
• Study Start: May 17, 2018
• Primary Completion: February 10, 2020
• Study Completion: February 10, 2020
• Last Updated: August 5, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)