Clinical Trials /

A Phase 1, Open-Label, Dose-Escalation Study of NEV801, Administered to Patients With Advanced Cancers

NCT02797795

Description:

This study is a first-in-human, multicenter, open-label, nonrandomized, dose-escalation trial to be conducted in 2 sequential parts: - Part A (Dose Escalation) in subjects with advanced malignancies - Part B (Dose Confirmation) in subjects with tumor type(s) to be determined by results of Part A

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1, Open-Label, Dose-Escalation Study of NEV801, Administered to Patients With Advanced Cancers
  • Official Title: A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Pharmacokinetics, and Clinical Effects of Intravenously Administered NEV801 in Subjects With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: NEV801-01
  • NCT ID: NCT02797795

Conditions

  • Advanced Cancer
  • Solid Tumors

Interventions

DrugSynonymsArms
NEV801NEV801

Purpose

This study is a first-in-human, multicenter, open-label, nonrandomized, dose-escalation trial to be conducted in 2 sequential parts: - Part A (Dose Escalation) in subjects with advanced malignancies - Part B (Dose Confirmation) in subjects with tumor type(s) to be determined by results of Part A

Detailed Description

      In Part A, subjects will be treated with a 30-minute intravenous (IV) infusion of NEV801 on
      Days 1, 8, 15, and 22 of continuous 28-day cycles. The starting dose of NEV801 will be 20
      mg/m2/dose, and the NEV801 dose will be escalated in successive cohorts of 3 subjects per
      dose level. In Part B, up to 3 expansion cohorts of up to 12 subjects each, defined by tumor
      type, will be enrolled at or below the MTD (i.e., the RP2D) of NEV801. In both parts,
      subjects who tolerate the drug and who do not experience progressive disease may continue to
      receive NEV801 at the discretion of the Investigator for up to 12 cycles. Subjects who
      tolerate the drug and experience clinical benefit will be eligible for further treatment in
      an extension protocol or through another means to be determined by the Sponsor.
    

Trial Arms

NameTypeDescriptionInterventions
NEV801ExperimentalPart A - Dose escalation and de-escalation for the determination of the Maximum tolerated dose. All subjects will receive NEV801 intravenously on days 1, 8, 15 and 22 during each 28-day cycle. Part B - Subjects will receive NEV801 at or below the highest tolerable dose from Part A.
  • NEV801

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female at least 18 years of age

          2. Willing and able to provide written informed consent and comply with the requirements
             of the study

          3. Pathologically confirmed advanced malignancy for which standard therapy proven to
             provide clinical benefit does not exist or is no longer effective

          4. Part A only: Evaluable disease, measurable either on physical examination or by
             imaging according to RECIST v1.1 or by informative tumor marker(s)

          5. Part B only: Selected tumor type(s), as determined by results of Part A

          6. Part B only: Measurable disease, using RECIST v1.1

          7. ECOG performance status of 0 or 1

        Exclusion Criteria:

          1. Receipt of more than 5 prior regimens of cytotoxic chemotherapy (unless prior approval
             is granted by the Sponsor)

          2. Any chemotherapy, immunomodulatory drug therapy, antineoplastic hormonal therapy,
             immunosuppressive therapy, corticosteroids > 20 mg/day prednisone or equivalent
             (unless administered to prevent contrast material reactions during radiographic
             procedures), or growth factor treatment (e.g., erythropoietin) within 14 days before
             first NEV801 dose

          3. Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of
             alopecia, that has not resolved to ≤ Grade 1, according to the NCI CTCAE v4.03

          4. Radiotherapy within 28 days before the first NEV801 dose

          5. Use within 7 days of the first NEV801 dose, or anticipated use, of agents that are
             strong inhibitors of CYP3A4, CYP1A2 and CYP2D6 enzymes (unless approved by the
             Sponsor) - see Section 5.6 for a list of strong CYP3A4, CYP1A2 and CYP2D6 inhibitors

          6. Use of any investigational agents within 28 days of the first NEV801 dose

          7. Major surgery within 28 days before the first NEV801 dose

          8. Life expectancy < 12 weeks

          9. Uncontrolled congestive heart failure (New York Heart Association Classification 3 or
             4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral
             artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3
             months before the first NEV801 dose

         10. History of or ongoing cardiac dysrhythmias requiring treatment, atrial fibrillation of
             any grade, or persistent prolongation of the QT corrected by the Fridericia formula
             (QTcF) interval to > 450 msec for males or > 470 msec for females

         11. Previous malignancy other than non-squamous-cell carcinoma of skin or carcinoma in
             situ of the uterine cervix (unless the tumor was treated with curative intent more
             than 2 years before the first NEV801 dose)

         12. Active bacterial, viral, or fungal infection requiring systemic therapy.

         13. Known HIV infection or AIDS-related illness

         14. Known active viral hepatitis

         15. Presence of genetic polymorphism of UGT1A1 leading to reduced glucuronidation

         16. Pregnant or lactating female

         17. Women of childbearing potential, unless they agree to use 2 contraceptive methods
             which, in the opinion of the Investigator, are effective and adequate for that
             subject's circumstances while on study drug and for 3 months afterward

         18. Men who partner with a woman of childbearing potential, unless they agree to use 2
             effective contraceptive methods (i.e., a condom, female partner using oral,
             injectable, or barrier method) while on study drug and for 3 months afterward

         19. Any severe, acute, or chronic medical or psychiatric condition, or laboratory
             abnormality that may increase the risk associated with study participation or NEV801
             administration; that may interfere with the informed consent process or with
             compliance with the requirements of the study; or that may interfere with the
             interpretation of study results and, in the Investigator's opinion, would make the
             subject inappropriate for entry into this study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:12 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Observe any antitumor effects of NEV801
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Neovia Oncology Ltd.

Last Updated

March 11, 2019