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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05619913


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT05619913
Ethics application status
Date submitted
26/10/2022
Date registered
17/11/2022

Titles & IDs
Public title
EPOCH: Eribulin and Pembrolizumab in Ovarian/Uterine Carcinosarcoma
Scientific title
The EPOCH Study: Phase II Open Labelled Study Investigating the Use of Single Agent Eribulin and Eribulin in Combination With Pembrolizumab in Relapsed Tubo-ovarian or Uterine Carcinosarcoma
Secondary ID [1] 0 0
ANZGOG 1828/2021
Universal Trial Number (UTN)
Trial acronym
EPOCH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Carcinosarcoma 0 0
Uterine Carcinosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eribulin Mesylate
Treatment: Drugs - Pembrolizumab

Experimental: Arm 1 - Single agent eribulin arm - 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.

Experimental: Arm 2 - Combination eribulin and pembrolizumab arm - 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.


Treatment: Drugs: Eribulin Mesylate
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.

Treatment: Drugs: Pembrolizumab
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).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Clinical Benefit Rate (CBR) by RECIST v1.1 in combination therapy arm
Timepoint [1] 0 0
12 Weeks
Secondary outcome [1] 0 0
Clinical Benefit Rate (CBR) by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 in single agent therapy arm
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
Objective Response Rate (ORR) in both the single agent eribulin and combination eribulin/pembrolizumab arms
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Clinical Benefit Rate (CBR) by iRECIST (modified RECIST guidelines for use in cancer immunotherapy trials)
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Time to progression in the combination therapy arm
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
Progression free survival (PFS)
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Overall Survival (OS)
Timepoint [6] 0 0
Up to 4 years
Secondary outcome [7] 0 0
Adverse events
Timepoint [7] 0 0
Up to 4 years
Secondary outcome [8] 0 0
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)
Timepoint [8] 0 0
Up to 4 years
Secondary outcome [9] 0 0
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)
Timepoint [9] 0 0
Up to 4 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/05/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
- Randwick
Recruitment postcode(s) [2] 0 0
- Herston
Recruitment postcode(s) [3] 0 0
- Clayton
Recruitment postcode(s) [4] 0 0
8006 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Ontario
Country [2] 0 0
United Kingdom
State/province [2] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Australia New Zealand Gynaecological Oncology Group
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Merck Sharp & Dohme LLC
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clare Scott, AM MB BS PhD
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clare Scott, AM MB BS PhD
Address 0 0
Country 0 0
Phone 0 0
+61 3 9345 2350
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05619913

Additional trial details provided through ANZCTR
Accrual to date
4
Recruiting in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 156
Peter MacCallum Cancer Centre
Recruitment hospital [2] 158
Royal Brisbane & Womens Hospital
Recruitment hospital [3] 159
Prince of Wales Hospital
Recruitment hospital [4] 160
Monash Medical Centre - Clayton campus
Recruitment postcode(s) [1] 156
3000
Recruitment postcode(s) [2] 157
3175
Recruitment postcode(s) [3] 158
4029
Recruitment postcode(s) [4] 159
2031
Recruitment postcode(s) [5] 160
3168
Funding & Sponsors
Primary sponsor
Other Collaborative groups
Primary sponsor name
Australia New Zealand Gynaecological Oncology Group
Primary sponsor address
Level 6, Lifehouse, 119-143 Missenden Road, Camperdown NSW 2050
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 64
PETER MACCALLUM CANCER CENTRE HUMAN RESEARCH ETHICS COMMITTEE
Address [1] 64
305 Grattan Street Melbourne Victoria 3000 Australia
Country [1] 64
Australia
Date submitted for ethics approval [1] 64
Approval date [1] 64
02/10/2023
Ethics approval number [1] 64
 
Public notes

Contacts
Principal investigator
Title 401 0
Prof
Name 401 0
Clare Scott
Address 401 0
Country 401 0
Australia
Phone 401 0
+61 3 9345 2350
Fax 401 0
Email 401 0
[email protected]
Contact person for public queries
Title 402 0
Mr
Name 402 0
John Andrews
Address 402 0
Country 402 0
Australia
Phone 402 0
+61 2 8071 4881
Fax 402 0
Email 402 0
[email protected]
Contact person for scientific queries
Title 403 0
Name 403 0
Address 403 0
Country 403 0
Phone 403 0
Fax 403 0
Email 403 0