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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04581512




Registration number
NCT04581512
Ethics application status
Date submitted
16/09/2020
Date registered
9/10/2020
Date last updated
3/01/2024

Titles & IDs
Public title
Study to Evaluate the Safety and Tolerability of EP0042
Scientific title
A Modular, Multipart, Multi-arm, Open-label, Phase I/IIa Study to Evaluate the Safety and Tolerability of EP0042 Alone and in Combination With Anti-cancer Treatments in Patients With Advanced Malignancies
Secondary ID [1] 0 0
EP0042-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Chronic Myelomonocytic Leukemia 0 0
Myelodysplastic Syndromes 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EP0042

Experimental: EP0042 -


Treatment: Drugs: EP0042
EP0042 Oral 20 mg 50 mg capsules
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period.
Timepoint [1] 0 0
First cycle of treatment (28 Days)

Eligibility
Key inclusion criteria
General:

1. Male or female patients aged = 18 years of age, at the time of informed consent, with
histological or cytological confirmation of an advanced malignancy

2. Ability to understand and provide written informed consent before any study-specific
procedures, sampling, or analyses, including access to archival tumour tissue

3. Ability to swallow and retain oral medication

4. Sufficient life expectancy to allow the patient to complete at least 1 cycle (28 days)
of the treatment period.

5. ECOG Performance Status of 0, 1 or 2 at Screening

6. In the opinion of the investigator, all other relevant medical conditions must be
well-managed and stable for at least 28 days prior to first administration of study
drug

Part A (escalation phase) only:

7. Patients with pathologically confirmed/documented AML or MDS, as defined by the 2017
European LeukaemiaNet (ELN) recommendations, or CMML, as defined by World Health
Organization (WHO) criteria, who have relapsed from or are refractory to previous
therapy

Part B (Expansion cohort patients) only:

8. Patients with pathologically confirmed/documented AML, as defined by the 2017 European
LeukaemiaNet (ELN) recommendations, who either decline or are unsuitable for standard
therapy, or who are refractory to, or have relapsed after, initial treatment, with no
more than 3 prior lines of therapy. A prior line of therapy is defined as:

- Treatment to induce remission with anthracycline/cytarabine (eg '3+7'
daunorubicin 60 mg/m2 [3 days/cycle] plus cytarabine 100-200 mg/m2 [7
days/cycle], +/-midostaurin

- mylotarg and including CPX-351, FLAG-ida or similar intensive regimens).

- Low dose cytarabine or hypomethylating agents (azacitidine or decitabine)

- Treatment with single agent FLT3 inhibitors (quizartinib, gilteritinib,
crenolanib) for relapsed disease

- Transplantation (allogeneic) in active disease.

The following is not considered a prior line of therapy:

- Consolidation cycles including those with midostaurin or mylotarg or quizartinib

- Transplantation (allogeneic) given during remission. Other prior treatments may
be discussed with the Medical Monitor for consideration.

Approximately 20 evaluable patients will be included with FLT-3 ITD AML and
approximately 10 evaluable patients with FLT-3 wild type AML, both confirmed by local
laboratories within 28 days prior to dosing

Contraception:

9. Female patients should either be of non-child-bearing potential or must agree to use
highly effective methods of contraception from Screening until 6 months following
administration of the last dose of study drug

10. Male patients must use double barrier contraception from enrolment through treatment
and for 6 months following administration of the last dose of study drug
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with any of the following will not be included in the study:

Disease Under Study and Prior Anticancer Treatment:

1. Suspected brain and/or leptomeningeal metastases that are symptomatic or untreated or
that require current therapy

2. Acute promyelocytic leukaemia (FAB:M3)

3. Systemic anti-cancer therapy for the disease under study within 4 weeks of the first
dose of study treatment. (Concomitant hydroxyurea is acceptable and will be permitted
throughout the screening period and during first 2 cycles of study treatment)

4. Ongoing toxic manifestations of previous treatments that have not reduced to at least
CTCAE Grade 1. Exceptions to this are alopecia or certain Grade 2 treatment related
toxicities, which in the opinion of the Investigator should not exclude the patient.

5. Transplantation (allogeneic or autologous) within last 90 days, or on active
immunosuppressive therapy for graft versus host disease in last 2 weeks Laboratory
Parameters

6. Patient with any out-of-range laboratory values defined as shown below. Haematology
evaluations must be performed =7 days from any blood or blood product transfusion and
=14 days from any dose of hematologic growth factor.

- Serum creatinine > 1.5 x upper limit of normal (ULN) and/or creatinine clearance
(calculated using Cockcroft-Gault formula, or measured) < 50 mL/min

7. Inadequate liver function as demonstrated by

- serum bilirubin =3 times the upper limits of normal range (ULN) or

- alanine aminotransferase (ALT) =3 times the ULN or

- aspartate aminotransferase (AST) =3 times the ULN or

- AST or ALT =5 times the ULN in the presence of liver involvement by leukaemia

Medical History and Concomitant Medications:

8. Confirmed QTcF > 470 msec on screening ECG or congenital long QT syndrome

9. Receiving an investigational anti-cancer treatment concurrently or within 14 days or
five half-lives of either the parent drug or any active metabolite prior to the start
of treatment with EP0042. Patients may receive hydroxyurea throughout the screening
period and during the first 2 cycles of study treatment.

10. Any evidence of severe or uncontrolled systemic or current unstable or uncompensated
respiratory or cardiac conditions which makes it undesirable for the patient to
participate in the study or which could jeopardize patient safety

11. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly
affecting gastrointestinal (GI) function, re-section of the stomach, extensive small
bowel re-section that is likely to affect absorption, symptomatic inflammatory bowel
disease, partial or complete bowel obstruction, or gastric restrictions and bariatric
surgery such as gastric bypass.

12. Known history of human immunodeficiency virus infection (HIV) (testing is not
required), active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
Testing for HBV or HCV status is not necessary unless clinically indicated or the
patient has a history of HBV or HCV infection

13. Hypersensitivity to EP0042 or D -a-Tocopherol polyethylene glycol succinate (TPGS)

14. Malignant disease other than that being treated in this study, with the following
exceptions:

- Malignancies that were treated curatively and have not recurred within 2 years
prior to study treatment

- Completely resected basal cell and squamous cell skin cancers

- Any malignancy considered to be indolent and that has never required therapy

- Completely resected carcinoma in situ of any type

15. Any medical condition that would, in the investigator's judgment, prevent the
patient's participation in the clinical study due to safety concerns, compliance with
clinical study procedures, or interpretation of study results

16. Any major surgical procedure (in the investigator's judgement) within 2 weeks of the
first dose of study drug (minimally invasive procedures such as bronchoscopy, tumour
biopsy, insertion of a central venous access device, and insertion of a feeding tube
are not considered major surgery and are not exclusionary)

17. Patients with a history of, or currently suffering from, severe psychiatric diseases
such as mania, manic depression or psychoses

18. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as
the state of a female after conception and until the termination of gestation)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Single group
Other design features
Phase
Phase 1/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
2/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2025
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
Netherlands
State/province [1] 0 0
Amsterdam
Country [2] 0 0
Netherlands
State/province [2] 0 0
Rotterdam
Country [3] 0 0
United Kingdom
State/province [3] 0 0
UK
Country [4] 0 0
United Kingdom
State/province [4] 0 0
London
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ellipses Pharma
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A research study looking at a new treatment for patients with advanced cancer, to investigate
different doses of the experimental study drug, EP0042, in order to determine a dose, which
is safe, well-tolerated and likely to be effective in treating AML (acute myeloid leukaemia).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04581512
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Taussig
Address 0 0
The Royal Marsden, UK
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Katie Stoddart
Address 0 0
Country 0 0
Phone 0 0
+44 (0) 2037430992
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04581512