Trial Title:
EPOCH: Eribulin and Pembrolizumab in Ovarian/Uterine Carcinosarcoma
NCT ID:
NCT05619913
Condition:
Ovarian Carcinosarcoma
Uterine Carcinosarcoma
Conditions: Official terms:
Carcinosarcoma
Mixed Tumor, Mullerian
Uterine Neoplasms
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Eribulin Mesylate
Description:
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.
Arm group label:
Arm 1 - Single agent eribulin arm
Arm group label:
Arm 2 - Combination eribulin and pembrolizumab arm
Other name:
Halaven
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
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).
Arm group label:
Arm 2 - Combination eribulin and pembrolizumab arm
Other name:
Keytruda
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.
Detailed description:
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).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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.
2. 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.
3. 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.
4. 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).
5. 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.
6. 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).
7. 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%).
8. 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.
9. Willing to have blood samples collected for translational research
10. Must not be pregnant, not breastfeeding, and at least one of the following
conditions applies:
1. Not a person of childbearing potential (POCBP). OR
2. A POCBP who agrees to follow the contraceptive guidance during the treatment
period and for at least 4 months (120 days) after the last dose of the study
treatment.
Exclusion Criteria:
1. 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.
2. Prior treatment with eribulin for any malignancy.
3. Absence of a second disease site suitable for biopsy
4. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to the first dose of the study intervention.
5. 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.
6. 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.
7. 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.
8. 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.
9. Symptomatic or clinically significant inflammatory bowel disease (Crohn's disease or
ulcerative colitis).
10. 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.
11. 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.
12. Has an active infection requiring systemic therapy.
13. Has had an allogenic tissue/solid organ transplant.
14. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients.
15. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
16. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: no
testing for HIV is required unless mandated by local health authority.
17. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA > 25 international
units/mL is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is
required unless mandated by local health authority.
18. Has a known additional active malignancy that is likely to interfere with assessment
of response or tolerance to the study intervention.
19. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
patients' participation for the full duration of the study, or is not in the best
interest of the patient to participate, in the opinion of the treating Investigator.
20. Inability to attend or comply with treatment or follow-up scheduling.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Prince of Wales Hospital
Address:
City:
Randwick
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Dr Yen Chen Lee
Email:
YehChen.Lee@health.nsw.gov.au
Facility:
Name:
Royal Brisbane and Women's Hospital
Address:
City:
Herston
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Dr Jeff Goh
Facility:
Name:
Monash Health
Address:
City:
Clayton
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Dr Gwo Ho
Email:
breastgynae.oncresearch@monashhealth.org
Facility:
Name:
Peter MacCallum Cancer Centre
Address:
City:
Melbourne
Zip:
8006
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Prof Clare Scott
Email:
PCCTU.Gynae@petermac.org
Facility:
Name:
Princess Margaret Hospital
Address:
City:
Toronto
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Amit Oza, Dr
Email:
Amit.Oza@uhn.ca
Facility:
Name:
Imperial College London
Address:
City:
London
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Dr Iain McNeish
Start date:
May 22, 2023
Completion date:
December 2026
Lead sponsor:
Agency:
Australia New Zealand Gynaecological Oncology Group
Agency class:
Other
Collaborator:
Agency:
Eisai Inc.
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Australia New Zealand Gynaecological Oncology Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05619913
