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NeoplasmsPhase 1/2NCT03138083

OMO-1 in Solid Malignancies

A Phase 1/2 study testing OMO-1 in people with Neoplasms, run by Octimet Oncology N.V. at 11 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
OMO-1
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
11 sitesin 5 countries
Study dates
8 Aug 2017to 25 May 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Performance status: Eastern Co-operative Oncology Group (ECOG) ≤1 and life expectancy ≥3 months.
  • Ability to swallow and retain oral medication.
  • Adequate organ functions.
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  • 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

Who cannot join

  • Patients receiving other cancer therapy, or other investigational product apart from the combination agent(s) described in the relevant combination modules.
  • Patients who have received radiotherapy for the primary tumour within 1 week from the screening visit.
  • Patients receiving medications predominantly metabolized by CYP2B6.
  • Patients receiving cannabinoid substances.
  • Patients receiving St John's Wort.
  • Patients receiving medications that are known to have potent aldehyde oxidase (AO) inhibitory activity.
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  • Patients with prior splenectomy.
  • Patients testing positive for human immunodeficiency virus (HIV) infection, hepatitis B based on findings of persistent hepatitis B virus surface antigen (HBsAg) or other serology test, hepatitis C virus (HCV) or Epstein-Barr Virus (EBV) infection.
  • Patients with current, or a history of uveitis.
  • 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.
  • 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 study treatment.
  • Patients with major and/or planned surgery within 12 weeks of the first dose of study treatment.
  • Patients with any known severe allergies (e.g., anaphylaxis) to any active or inactive ingredients in OMO-1.
  • Patients with nephrolithiasis.
  • Patients with current, or a history of any seizure or seizure disorder. This includes receiving, or having received, seizure threshold-raising medication for the treatment of epilepsy.
  • In addition to the main core eligibility criteria, Module specific eligibility criteria include:
  • Module 1:
  • Patient recruited into the paired biopsy cohorts of Part A must have:
  • at least 1 lesion suitable for biopsy.
  • tumours that are MET gene amplified and/or mutated.
  • had no prior therapy with a selective MET inhibitor.
  • Patients recruited into Part B cohorts must have:
  • tumours that are MET gene amplified and/or mutated.
  • at least one lesion, not previously irradiated, that can be accurately measured at baseline.
  • had no prior therapy with a selective MET inhibitor.
  • no coinciding malignancy that would impact on survival.
  • no metastasis limited to the bone only.
  • Module 2:
  • Patients recruited into Part A and Part B cohorts must have:
  • tumours that are EGFR gene mutant that are currently progressing on treatment with a small molecule EGFR-TKI. Enrolment must be restricted to patients that are resistant to all relevant EGFR TKI therapy according to their tumour mutated status.
  • received the EGFR-TKI as monotherapy for at least 12 weeks.
  • tolerated their current dose of EGFR-TKI for at least 12 weeks.
  • tumours that are MET gene amplified.
  • had no prior therapy with a selective MET inhibitor.
  • had no prior EGFR-TKI treatment of >2 lines.
  • no past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
  • no significant GI disorders with diarrhoea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE Grade >1 diarrhoea of any aetiology at the enrolment.
  • no contra-indications (as per the relevant medication package insert) for therapy with the EGFR-TKI routinely used by their oncology unit.
  • In addition, patients recruited into Module 2 Part B cohorts must have:
  • at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with CT or MRI and which is suitable for accurate repeated assessment.
  • no coinciding malignancy that would impact on survival.
  • no metastasis limited to the bone only.

Trial locations and contacts

11 sites in 5 countries.

11 sites in 5 countries

United Kingdom4 sites

  • University College London Hospitals NHS Foundation Trust

    London

  • The Christie NHS Foundation Trust

    Manchester

  • The Newcastle Upon Tyne Hospitals NHS Foundation Trust

    Newcastle upon Tyne

  • University of Oxford, Department of Oncology

    Oxford

Other trials in United Kingdom

France3 sites

  • Institut Bergonie

    Bordeaux

  • Hôpital La Timone

    Marseille

  • lnstitut Gustave Roussy

    Villejuif

Other trials in France

Netherlands2 sites

  • Erasmus MC

    Rotterdam

  • UMCU Universitair Medisch Centrum Utrecht

    Utrecht

Other trials in Netherlands

United States1 site

  • Mary Crowley Cancer Research

    Dallas, Texas, 75251

Other trials in United States

Belgium1 site

  • University Hospital Antwerp

    Edegem

Other trials in Belgium

About this study

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

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.

Read the detailed description

The study will consist of a number of study modules. The initial Module 1 will evaluate OMO-1 as monotherapy to provide dose(s) and schedule(s) for further Modules of combination therapy.

Module 2 will evaluate OMO-1 in combination with small molecule EGFR-TKIs.

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.

For all modules, Part A cohorts 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 paired 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.

Conditions
Neoplasms
Being tested
OMO-1
Keywords
Mesenchymal-epithelial transition factor (MET) inhibitor
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OMO-1Drug

    Also called JNJ-38877618

    OMO-1 is a small molecule inhibitor of the enzymatic activity of the MET receptor tyrosine kinase

Study groups in NCT03138083
Study groupRoleWhat they receive
Module 1 Monotherapy Multiple Ascending DoseExperimentalMultiple ascending dose cohorts dosing OMO-1 (bid) monotherapy in all comer patients up to a maximally tolerated or maximally feasible dose
Receives: Drug: OMO-1
Module 1 Monotherapy Paired BiopsyExperimentalPaired biopsy cohort(s) dosing OMO-1 (bid) monotherapy in patients selected for MET dependent tumours at minimally biologically active doses and above
Receives: Drug: OMO-1
Module 1 Monotherapy Expansion Cohort(s)ExperimentalExpansion cohort(s) dosing OMO-1 (bid) monotherapy in patients selected for MET dependent tumours at recommended phase 2 dose (RP2D)
Receives: Drug: OMO-1
Module 2 Combination with EGFR-TKI Multiple Ascending DoseExperimentalMultiple ascending dose cohorts dosing OMO-1 (bid) in combination with EGFR-TKI in MET amplified patients up to a maximally tolerated or maximally feasible dose
Receives: Drug: OMO-1
Module 2 Combination with EGFR-TKI Paired BiopsyExperimentalPaired biopsy cohort(s) dosing OMO-1 (bid) in combination with EGFR-TKI in MET amplified patients at minimally biologically active doses and above
Receives: Drug: OMO-1
Module 2 Combination with EGFR-TKI Expansion CohortExperimentalExpansion cohort dosing OMO-1 (bid) monotherapy in combination with EGFR-TKI in MET amplified patients at recommended phase 2 (combination) dose (RP2D)
Receives: Drug: OMO-1

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of treatment-emergent adverse events including dose-limiting toxicities

    The proportion of patients with treatment-emergent (serious) adverse events including dose-limiting toxicity (DLT)

    Measured: Baseline (C1D1) until 28 days after last administration of OMO-1

  2. Incidence of clinically significant abnormal measurements in physical examination, ophthalmological examination, vital signs, electrocardiogram (ECG), pregnancy test, lab tests and ECOG performance status

    Physical examination and ophthalmological examination, vital signs; electrocardiogram (ECG); pregnancy test; haematology; clinical chemistry; urinalysis; plasma/renal makers; tumour markers; ECOG performance status

    Measured: Screening until 28 days after last administration of OMO-1

Secondary outcomes (5)

  1. Objective Response Rate

    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).

    Measured: Screening until 28 days after last administration of OMO-1

  2. Percentage change in tumour size

    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.

    Measured: Screening until 28 days after last administration of OMO-1

  3. Maximal OMO-1 plasma concentration Cmax

    Measurement of OMO-1 levels in plasma over time to calculate Cmax

    Measured: Baseline (C1D1) and D1 in even cycles (C) until end of treatment (Part A) ; Baseline and C2D1 (Part B)

  4. Area under the OMO-1 plasma concentration curve (AUC)

    Measurement of OMO-1 levels in plasma over time to calculate AUC

    Measured: Baseline (C1D1) and D1 in even cycles (C) until end of treatment (Part A) ; Baseline and C2D1 (Part B)

  5. 'Proof of mechanism' and 'proof of principle' pharmacodynamic biomarkers, including markers of tumour cell proliferation and apoptosis.

    Measurement of levels of 'Proof of mechanism' and 'proof of principle' pharmacodynamic biomarkers, including markers of tumour cell proliferation and apoptosis.

    Measured: Screening until end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2017
  2. Study start8 Aug 2017
  3. Primary completion25 May 2020
  4. Study completion25 May 2020

Why it stopped: strategic reasons (not due to lack of efficacy or safety issues)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
A modular, multi-arm, multi-part, first time in patient study
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03138083
Sponsor's protocol ID
OMO1.01.02
Status last verified
Jun 2020
First submitted
26 Apr 2017
Last updated
11 Jun 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing OMO-1 in people with Neoplasms, run by Octimet Oncology N.V. at 11 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United Kingdom, France, Netherlands, United States, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: strategic reasons (not due to lack of efficacy or safety issues)). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment-emergent adverse events including dose-limiting toxicities (time frame: Baseline (C1D1) until 28 days after last administration of OMO-1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03138083.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2020.

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