EPOCH: Eribulin and Pembrolizumab in Ovarian/Uterine Carcinosarcoma

NCT05619913 | Recruiting Phase 2 DMC

• 1 other identifier: ANZGOG 1828/2021
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 6

Brief Summary

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.

Conditions

Ovarian Carcinosarcoma; Uterine Carcinosarcoma

Outcome Measures

Primary Outcomes (1)

• Clinical 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.

  12 Weeks

Secondary Outcomes (9)

• Clinical Benefit Rate (CBR) by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 in single agent therapy arm

  12 weeks

• Objective Response Rate (ORR) in both the single agent eribulin and combination eribulin/pembrolizumab arms

  12 weeks

• Clinical Benefit Rate (CBR) by iRECIST (modified RECIST guidelines for use in cancer immunotherapy trials)

  12 weeks

• Time to progression in the combination therapy arm

  Up to 3 years

• Progression free survival (PFS)

  Up to 4 years

Other Outcomes (2)

• Duration of response

  Up to 4 years

• High mobility group A2 (HMGA2) protein expression

  Up to 4 years

Study Arms (2)

Arm 1 - Single agent eribulin arm

EXPERIMENTAL

Eribulin until progression of disease (PD) as defined by RECIST v1.1, unacceptable toxicity or physician/patient discretion or choice to cease treatment. Patients who progress on the single agent eribulin arm may receive combination eribulin and pembrolizumab.

Drug: Eribulin Mesylate

Arm 2 - Combination eribulin and pembrolizumab arm

EXPERIMENTAL

Eribulin for a maximum of 6 cycles. Pembrolizumab until PD or a maximum of 35 cycles (including the 6 cycles where it is administered in combination with eribulin) or until unacceptable toxicity or physician/patient discretion or choice to cease treatment.

Drug: Eribulin Mesylate; Drug: Pembrolizumab

Interventions

Eribulin Mesylate DRUG

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.

Also known as: Halaven

Arm 1 - Single agent eribulin arm; Arm 2 - Combination eribulin and pembrolizumab arm

Pembrolizumab DRUG

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).

Also known as: Keytruda

Arm 2 - Combination eribulin and pembrolizumab arm

Eligibility Criteria

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

You may qualify if:

• Provision of written informed consent prior to any study specific procedures and the ability to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations.
• Patients \> 18 years old who have a histologically confirmed tubo-ovarian carcinosarcoma or uterine carcinosarcoma with evidence of recurrence or progression. The component of sarcoma in the diagnostic pathology sample must be equal to or \> 5% of tumour.
• Must have Positron Emission Tomography (PET), Computerized Tomography CT, or Magnetic Resonance Imaging (MRI) -proven relapsed disease after completion of at least one line and not more than two lines of chemotherapy.
• Must have at least one evaluable measurable lesion (other than the lesion that will be used for biopsy) using standard techniques according to the Response Evaluation Criteria in Solid Tumours (RECIST v1.1) guidelines (Appendix 1).
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Appendix 5). Evaluation of ECOG is to be performed within 28 days prior to the first dose of the study intervention.
• Have adequate organ function as defined below (refer also Appendix 6).
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Platelets ≥100 x 109/L
• Haemoglobin (Hb) ≥90 g/L or ≥5.6 mmol/L (criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks).
• Creatinine ≤ 1.5 x Upper Limit Normal (ULN); OR Creatinine Clearance (CrCl) ≥ 30 mL/min (calculated per institutional standard) for participants with creatinine levels \>1.5 ULN (glomerular filtration rate, GFR, can also be used in place of creatinine or CrCl). (Patients with moderate renal impairment (CrCl 30-49ml/min) will receive a 25% reduced dose of eribulin).
• Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
• Alkaline phosphatase (ALP), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
• International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants Biological specimens must be collected within 28 days prior to the first dose of the study intervention (within 7 days, where indicated in the SoA).
• Available formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer and/or metastatic tumour from the up-front or secondary debulking surgery with adequate neoplastic cell content (\>30%).
• Must have disease amenable to biopsy and must be willing to undergo a paired biopsy for additional correlative analyses (the first biopsy to be performed within 28 days prior to the start of the study intervention and the second biopsy in the five-day window prior to Cycle 2 (post Cycle 1)). For patients that experience progression of their disease whilst on study, separate patient consent will be sought for additional biopsies of their tumour for research.

You may not qualify if:

• Prior line of treatment involving immunotherapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor. This criteria is applicable for both intervention arms as patients may cross-over from the non-immunotherapy arm during their study participation.
• Prior treatment with eribulin for any malignancy.
• Absence of a second disease site suitable for biopsy
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the first dose of the study intervention.
• Has active autoimmune disease (such as Systemic Lupus Erythematosus) that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• A POCBP who has a positive urine pregnancy test within 7 days prior to the first dose of the study intervention (see Appendix 7). If the urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior radiotherapy within 2 weeks of the start of the study intervention. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system disease.
• Known central nervous system malignancy or metastasis, including leptomeningeal metastasis or carcinomatous meningitis, unless adequately treated and patients are neurologically stable for at least one month prior to enrolment. Patients must be either off corticosteroids or on stable or decreasing dose of \< /=10 mg daily prednisone (or equivalent) within 28 days prior to the first dose of the study intervention. In the case of short-term use of systemic corticosteroids (less than 24 hours within 28 days) of greater than 10 mg daily of prednisone or an equivalent corticosteroid, the required washout period prior to starting the first dose of the study intervention is 7 days. Anticonvulsants are allowed to be continued except for those which interfere with the study interventions or are associated with liver toxicity. However, patients receiving anticonvulsants must be discussed with Study Chair or Acting Chair of Trial Management Committee (TMC) prior to their enrolment to the study.
• Symptomatic or clinically significant inflammatory bowel disease (Crohn's disease or ulcerative colitis).
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study intervention.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of the study intervention. Live vaccine or live-attenuated vaccine cannot be administered during treatment with the study intervention and for 30 days post discontinuation of the study intervention. Administration of killed vaccines is allowed.
• Has an active infection requiring systemic therapy.
• Has had an allogenic tissue/solid organ transplant.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Sponsors & Collaborators

• Australia New Zealand Gynaecological Oncology Group: lead
• Eisai Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (6)

Prince of Wales Hospital

Randwick, New South Wales, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

RECRUITING

Monash Health

Clayton, Victoria, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 8006, Australia

RECRUITING

Princess Margaret Hospital

Toronto, Ontario, Canada

RECRUITING

Imperial College London

London, United Kingdom

NOT YET RECRUITING

MeSH Terms

Interventions

eribulin; pembrolizumab

Study Officials

• Clare Scott, AM MB BS PhD

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clare Scott, AM MB BS PhD

CONTACT

+61 3 9345 2350; scottc@wehi.edu.au

John Andrews

CONTACT

+61 2 8071 4881; EPOCH@anzgog.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2022
• First Posted: November 17, 2022
• Study Start: May 22, 2023
• Primary Completion: March 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); GB (1); AU (4)