Clinical Trials /

Study to Evaluate the Safety and Tolerability of EP0042

NCT04581512

Description:

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).

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Safety and Tolerability of EP0042
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: EP0042-101
  • NCT ID: NCT04581512

Conditions

  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
EP0042EP0042

Purpose

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 Arms

NameTypeDescriptionInterventions
EP0042Experimental
  • EP0042

Eligibility Criteria

        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

        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 -α-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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period.
Time Frame:First cycle of treatment (28 Days)
Safety Issue:
Description:Incidence of dose-limiting toxicities (DLT)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ellipses Pharma

Last Updated

October 5, 2020