Clinical Trials /

OMO-1 in Solid Malignancies

NCT03138083

Description:

This is a modular, first time in patient, open-label, multicentre study of OMO-1, administered orally, alone and in combination with anti-cancer treatments, in patients with locally advanced, unresectable or metastatic solid malignancies.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: OMO-1 in Solid Malignancies
  • Official Title: A Modular, Multi-arm, Multi-part, First Time in Patient Study to Evaluate the Safety and Tolerability of OMO-1, Alone and in Combination With Anti-cancer Treatments, in Patients With Locally Advanced, Unresectable or Metastatic Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: OMO1.01.02
  • NCT ID: NCT03138083

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
OMO-1JNJ-38877618Multiple Ascending Dose

Purpose

This is a modular, first time in patient, open-label, multicentre study of OMO-1, administered orally, alone and in combination with anti-cancer treatments, in patients with locally advanced, unresectable or metastatic solid malignancies.

Detailed Description

      The study will consist of a number of study modules - the first of which is Module 1.

      Combination study modules will consist of a Part A (dose finding) and an optional Part B
      (cohort expansion). The option to start Part B and add further modules will be the decision
      of the safety review committee, based on emerging preclinical anti-tumour data and, safety
      and tolerability information from the study as a whole. A substantial protocol amendment
      with relevant preclinical and emerging clinical data will be put in place before starting a
      new combination module.

      The initial dosing schedule and/or sequence of OMO-1 in each module may be subsequently
      changed between patient cohorts in response to emerging safety, pharmacokinetic (PK) and
      pharmacodynamic (PDc) findings. The maximum tolerated dose (MTD) of OMO-1 for individual
      modules may therefore differ based on the emerging safety profile for each combination.

      Once a minimally biologically active dose (MBAD) of OMO-1 for a module has been identified
      from Part A of that module, the safety review committee may decide to commence Part B. This
      may include cohort expansions of specific patient groups to explore preliminary anti-tumour
      activity or the effect of food or particular drug combinations on drug PK.

      For all modules, Part A cohorts (dose escalation) may be expanded by up to 12 additional
      patients at doses (at or above the MBAD) that have been confirmed to be tolerated. These
      patients will have mandatory serial biopsies to assess the tumour for relevant PDc
      biomarkers, and to explore further the tolerability, safety and PK activity at these doses.

      In all combination modules, the dose of each combination agent investigated will not exceed
      their current recommended dose. The starting dose of OMO-1 in combination modules will not
      exceed the one currently tolerated in Module 1 (monotherapy). For cohorts in which OMO-1 is
      dosed in combination with cytotoxic chemotherapy, dosing will not continue once the cycles
      of chemotherapy have been completed.
    

Trial Arms

NameTypeDescriptionInterventions
Multiple Ascending DoseExperimentalmultiple ascending dose of OMO-1 (bid) in all comer patients up to a maximally tolerated or maximally feasible dose
  • OMO-1
biopsyExperimentalpaired biopsies in patients selected for MET dependent tumours at minimally biologically active doses and above
  • OMO-1
Monotherapy dose extensionExperimentalMonotherapy Extension of maximal tolerable or maximal feasible dose
  • OMO-1

Eligibility Criteria

        Inclusion Criteria:

          -  Aged at least 18 years

          -  Provision of signed and dated, written informed consent.

          -  Histological or cytological confirmation of locally advanced, unresectable or
             metastatic solid malignancy not considered by the Investigator to be appropriate for
             further conventional treatment.

          -  Performance status: Eastern Co-operative Oncology Group (ECOG) ≤1 and life expectancy
             ≥3 months.

          -  Ability to swallow and retain oral medication.

          -  Adequate organ functions.

          -  Females of child-bearing potential:

               -  Must use a highly effective method contraceptive measures during the study and
                  for 1 month after the last dose of OMO 1.

               -  Must not be breast feeding.

               -  Must have a negative pregnancy test prior to start of dosing.

          -  Sexually active male patients must be willing to use barrier contraception

        In addition to the main core eligibility criteria, module specific eligibility criteria
        include:

        Module 1:

        Patient recruited into the sequential biopsy cohorts of Part A:

        At least 1 lesion suitable for biopsy. Tumours that are MET gene amplified and/or mutated.
        No prior therapy with a selective MET inhibitor.

        Patients recruited into Part B cohorts:

        Tumours that are MET gene amplified and/or mutated. At least one lesion, not previously
        irradiated, that can be accurately measured at baseline.

        No prior therapy with a selective MET inhibitor. No history of other malignancy (except
        non-melanoma skin carcinoma and carcinoma-in-situ of the uterine cervix) within 5 years
        prior to the first dose of OMO-1.

        No metastasis limited to the bone only.

        Exclusion Criteria:

          1. Patients receiving other cancer therapy, or another investigational product
             Bisphosphonates and granulocyte-colony stimulating factor (GCSF) are acceptable.
             Hormone replacement therapy (HRT) and stable treatment of >6 months with luteinizing
             hormone releasing hormone (LHRH) analogues are acceptable.

          2. Patients who have received radiotherapy within 1 week of the first dose of OMO-1.

          3. Patients receiving metformin.

          4. Patients receiving medication that may have aldehyde oxidase (AO) inhibitory activity
             e.g. Raloxifene

          5. Patients with prior splenectomy.

          6. Patients with a history of human immunodeficiency virus (HIV) infection, persistent
             hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) or Epstein-Barr
             Virus (EBV) infection.

          7. Patients with current, or a history of uveitis.

          8. Patients with any known uncontrolled inter-current illness including ongoing or
             active infections, symptomatic congestive heart failure, conditions that could
             adversely be affected by hypertension or tachycardia, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements.

          9. Patients with a history or clinical evidence of neoplastic central nervous system
             (CNS) involvement if not stable for 9 weeks prior to the first dose of OMO-1.

         10. Patients with major and/or planned surgery within 12 weeks of the first dose of
             OMO-1.

         11. Patients with pleural effusions and/or ascites, due to malignancy, requiring
             paracentesis every 2 weeks or more frequently.

         12. Patients with any known severe allergies (e.g., anaphylaxis) to any active or
             inactive ingredients in OMO-1.

         13. Patients with abnormal urinary function and outflow obstruction.

             In addition, the following are criteria for exclusion from the optional exploratory
             genetic research:

         14. Patients with previous allogenic bone marrow transplant.

         15. Patients with non-leukocyte depleted whole blood transfusion within 120 days of the
             date of the genetic sample collection.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:baseline until 28 days after last administration of OMO-1
Safety Issue:
Description:Physical examination and ophthalmological examination, vital signs; electrocardiogram (ECG); pregnancy test; haematology; clinical chemistry; urinalysis; plasma/renal makers; tumour markers; ECOG performance status; dose-limiting toxicity (DLT); adverse events (AEs). dose-limiting toxicity (DLT); adverse events (AEs).

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:baseline until 28 days after last administration of OMO-1
Safety Issue:
Description:Objective response rate (ORR) by RECIST 1.1 - the proportion of patients with a confirmed reduction in tumour burden of a predefined amount (this will include short lived responses).
Measure:Percentage change in tumour size
Time Frame:baseline until 28 days after last administration of OMO-1
Safety Issue:
Description:Percentage change in tumour size will be determined for patients with measurable disease at baseline and is derived at each visit by the percentage change from baseline in the sum of the diameters of target lesions. The best percentage change in tumour size will be the patient's value representing the largest decrease (or smallest increase) from baseline in tumour size.
Measure:Maximal OMO-1 plasma concentration Cmax
Time Frame:Day1 and Day21
Safety Issue:
Description:
Measure:Area under the OMO-1 plasma concentration curve (AUC)
Time Frame:Day1 and Day21
Safety Issue:
Description:
Measure:'Proof of mechanism' and 'proof of principle' pharmacodynamic biomarkers, including markers of tumour cell proliferation and apoptosis.
Time Frame:Baseline, day 3 and week 18 (end of treatment)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Octimet Oncology N.V.

Trial Keywords

  • Mesenchymal-epithelial transition factor (MET) inhibitor

Last Updated

May 8, 2017