The EPOCH study population is patients with tubo-ovarian carcinosarcoma or uterine carcinosarcoma with evidence of recurrence or progression. The study aims to determine the activity of eribulin as a single agent and the combination of eribulin and pembrolizumab as measured by clinical benefit rate (CBR) at 12 weeks. Additionally, the study aims to establish whether high mobility group A2 (HMGA2) protein expression is a good functional biomarker to predict response to eribulin and pembrolizumab.
EPOCH (Eribulin and Pembrolizumab in Tubo-Ovarian and Uterine Carcinosarcoma) is an international clinical trial, which aims to improve outcomes in people with the rare and highly lethal Ovarian Carcinosarcoma (OCS) or Uterine Carcinosarcoma (UCS) malignancies. The underlying study rationale is based on robust preclinical evidence that demonstrated that eribulin, a microtubule inhibitor, can reprogram the tumour microenvironment, reversing epithelial mesenchymal transition (EMT) in these mesenchymal cancers, and potentiate the response to immune checkpoint blockade. In addition, expression of HMGA2, a high mobility group protein has been associated with activation of EMT process and may be a predictive biomarker of eribulin-responsive cancers. This study is aimed at translating these laboratory findings to the clinic and treat patients with recurrent OCS and UCS with eribulin and the immune checkpoint inhibitor pembrolizumab, which targets and blocks the programmed cell death receptor 1 (PD-1).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Eribulin mesilate is a first-in-class halichondrin B-based, microtubule dynamics inhibitor7. It inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into non-productive aggregates.
Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD 1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2).
Prince of Wales Hospital
Randwick, New South Wales, Australia
RECRUITINGRoyal Brisbane and Women's Hospital
Herston, Queensland, Australia
RECRUITINGMonash Health
Clayton, Victoria, Australia
RECRUITINGPeter MacCallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGPrincess Margaret Hospital
Toronto, Ontario, Canada
RECRUITINGImperial College London
London, United Kingdom
NOT_YET_RECRUITINGClinical Benefit Rate (CBR) by RECIST v1.1 in combination therapy arm
CBR defined as Partial Response (PR), Complete Response (CR) or Stable Disease (SD) by RECIST v1.1 in the combination therapy arm.
Time frame: 12 Weeks
Clinical Benefit Rate (CBR) by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 in single agent therapy arm
CBR defined as Partial Response, Complete Response or Stable Disease by RECIST v1.1 in the single agent therapy arm.
Time frame: 12 weeks
Objective Response Rate (ORR) in both the single agent eribulin and combination eribulin/pembrolizumab arms
Objective Response Rate (CR and PR by RECIST v1.1) at 12 weeks in both the single agent eribulin and combination eribulin/pembrolizumab arms
Time frame: 12 weeks
Clinical Benefit Rate (CBR) by iRECIST (modified RECIST guidelines for use in cancer immunotherapy trials)
Clinical Benefit Rate (CR and PR and SD) by irRECIST at 12 weeks in both the single agent eribulin and combination eribulin/pembrolizumab arms
Time frame: 12 weeks
Time to progression in the combination therapy arm
Determine time to progression in the combination therapy arm
Time frame: Up to 3 years
Progression free survival (PFS)
Determine progression free survival (PFS)
Time frame: Up to 4 years
Overall Survival (OS)
Determine Overall Survival (OS)
Time frame: Up to 4 years
Adverse events
Determine toxicity, frequency, and severity of Adverse Events (CTCAE V5.0)
Time frame: Up to 4 years
Health related Quality of Life using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for cancer patients (QLQ C30)
Determine aspects of health-related quality of life using EORTC QLQ C30
Time frame: Up to 4 years
Health related Quality of Life using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire module for Ovarian Cancer patients (OV28)
Determine aspects of health-related quality of life using EORTC OV28
Time frame: Up to 4 years
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