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A Randomised Phase II Open-label Study With a Phase Ib Safety lead-in Cohort of ONCOS-102, an Immune-priming GM-CSF Coding Oncolytic Adenovirus, and Pemetrexed/Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma

Primary Purpose

To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With Chemotherapy

Status
Unknown status
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ONCOS-102
Pemetrexed/cisplatin (carboplatin)
Cyclophosphamide
Sponsored by
Targovax Oy
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With Chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Written informed consent.
  • Male or female, ≥18 years of age.
  • Histologically confirmed unresectable (advanced) malignant pleural mesothelioma in patients who are not candidates for curative surgery and for whom therapy with pemetrexed in combination with cisplatin or carboplatin is considered appropriate. This include:

    • patients who are naïve to chemotherapy,
    • and those who have already received pemetrexed in combination with cisplatin or carboplatin to which their tumour initially responded, but they have relapsed after at least 6 months.

The patient may be evaluated by a multidisciplinary consultation (according to hospital procedure), however the final decision about the inclusion of a patient is made by the principal investigator.

  • Measurable disease according to Response Evaluation in Solid Tumour (RECIST 1.1).
  • Tumour must be accessible to intratumoural (i.t.) injections and to tumour core needle biopsy or thoracoscopy for tissue sampling and immunohistochemistry analysis.
  • The patients must be eligible to receive the study specific chemotherapies, including cyclophosphamide, according to the SPCs and local practice.
  • Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance score 0 to 1.
  • Acceptable liver, renal, and haematological functions.
  • All women of childbearing potential must have a negative urine or serum pregnancy test at screening and all patients must agree to use barrier contraception (i.e. condom) during study treatment and for 2 months after the last virus treatment, 6 months after the last dose of pemetrexed/cisplatin/carboplatin and 12 months after the dose of cyclophosphamide.

Exclusion Criteria:

  • Receipt of oncolytic virus treatment, or vaccination with a vaccine containing live virus within 4 weeks before Day 1.
  • Use of significant immunosuppressive medication, including high dose corticosteroid (defined as the equivalent of >10 mg/day prednisone) within 4 weeks before Day 1.
  • Patients who participated in a study with an investigational drug or device within 4 weeks prior to Day 1.
  • Active bacterial, viral, or fungal infections, requiring systemic therapy.
  • Severe arrhythmia, heart failure, previous cardiac infarction, or acute inflammatory heart disease.
  • Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient, if included in this study.
  • Known infection with HIV, hepatitis B, or hepatitis C.
  • Known brain metastases.
  • History of organ transplant.
  • Females who are pregnant or breast feeding.
  • Unwillingness or inability to comply with the study protocol for any reason.
  • Patients with pre-existing hearing loss or neuropathy that may worsen due to potential neurotoxicity from cisplatin.
  • Patients with a history of hypersensitivity to cisplatin or carboplatin or pemetrexed or cyclophosphamide (or any of its metabolites).
  • Patients who are taking phenytoin for prophylactic use.
  • History of malignant tumour, unless the patient has been without evidence of disease for at least 3 years, or the tumour was a non-melanoma skin tumour, cervical carcinoma in situ, or prostatic carcinoma in situ.

Sites / Locations

  • Centre Georges-François Leclerc
  • CHU de Rennes - Pontchaillou
  • Hospital Universitario Quirón
  • Vall d'Hebron Univerity Hospital
  • Hospital Universitari de Girona Doctor Josep Trueta - Institut Català d'Oncologia
  • Hospital 12 de octubre
  • Hospital Universitario HM Sanchinarro

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ONCOS-102+cyclophosphamide+pemetrexed/cisplatin (carboplatin)

Pemetrexed/cisplatin (carboplatin)

Arm Description

ONCOS-102 will be administered in a priming cycle (Cycle 1) comprising injections on Days 1, 4, 8 and 36, followed by two treatment cycles at intervals of 6 weeks (Cycle 2, Day 78 and Cycle 3, Day 120). Pre-treatment with an i.v. bolus of cyclophosphamide (CPO) will be given 1 to 3 days before the first administration of ONCOS-102 (Cycle 1, Day 1) and before administration of Cycle 2 of ONCOS-102 (Day 78). Patients will also receive pemetrexed/cisplatin (carboplatin) in 21-day cycles starting on Day 22 and continuing as applicable during the study period of 6 cycles of pemetrexed/cisplatin (carboplatin) in combination with ONCOS-102.

Patients will be treated with pemetrexed/cisplatin (carboplatin) in 21-day cycles starting on Day 1, and continuing as applicable during the study period of 6 cycles of chemotherapy. Patients will be monitored regularly for immunological assessment (PBMCs) including Month 9 and Month 12 (i.e., after the end of study visit), and will be followed up for survival every 3 months until end of life.

Outcomes

Primary Outcome Measures

Number of patients with any (Serious and Non-Serious) Adverse Event measured to assess safety and tolerability

Secondary Outcome Measures

To determine and compare tumour-specific immunological activation in the peripheral blood in the experimental group and the control group. Number of patients in the respective arms with induction of Tumor specific CD8+ T Cells in PBMC
To determine and compare immunological activation in tumour mass in the experimental group and the control Group. Number of patients in the respective arms with infiltration of CD8+ T Cells into tumours
To determine and compare overall response rate in the experimental group and the control group by number of patients with PD, SD, PR and CR in the respective arms
To determine and compare progression-free survival (PFS) in the experimental group and the control group by median time to progression in the respective arms
To determine and compare overall survival (OS) in the experimental group and the control group
To analyse immunological activation by comparing patients with and without presence of tumour antigen recognizing CD8+ T cells
To analyse clinical outcome by time to event endpoints (OS and PFS)

Full Information

First Posted
July 13, 2016
Last Updated
October 6, 2020
Sponsor
Targovax Oy
Collaborators
Theradex
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1. Study Identification

Unique Protocol Identification Number
NCT02879669
Brief Title
A Randomised Phase II Open-label Study With a Phase Ib Safety lead-in Cohort of ONCOS-102, an Immune-priming GM-CSF Coding Oncolytic Adenovirus, and Pemetrexed/Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma
Official Title
A Randomised Phase II Open-label Study With a Phase Ib Safety lead-in Cohort of ONCOS-102, an Immune-priming GM-CSF Coding Oncolytic Adenovirus, and Pemetrexed/Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
June 2016 (undefined)
Primary Completion Date
May 2020 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Targovax Oy
Collaborators
Theradex

4. Oversight

5. Study Description

Brief Summary
The trial is an open-label, parallel group, multicentre trial that will recruit a total of 30 patients with malignant pleural mesothelioma. The trial will be conducted in 2 phases: a non-randomised safety phase and a randomised phase. The safety phase will consist of a lead-in cohort of 6 patients treated with ONCOS 102 and pemetrexed/cisplatin. The randomised phase will not commence until the DSMB has deemed the safety lead-in data appropriate for continuation. A total of 24 patients will be included in the randomised phase; 14 patients will be randomised to receive ONCOS 102 and pemetrexed/cisplatin, and 10 patients will receive pemetrexed/cisplatin alone. If cisplatin is seen to be too toxic after one or more cycles, the patient may change to carboplatin during the study. Furthermore, if treatment with cisplatin is deemed to be too toxic by the investigator due to age, presence of neurological toxicities or other relevant medical conditions, carboplatin can be administered from start of study. The trial's main objectives are determination of safety, immune activation, clinical response and the correlation between clinical outcome and the immunological data.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With Chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ONCOS-102+cyclophosphamide+pemetrexed/cisplatin (carboplatin)
Arm Type
Experimental
Arm Description
ONCOS-102 will be administered in a priming cycle (Cycle 1) comprising injections on Days 1, 4, 8 and 36, followed by two treatment cycles at intervals of 6 weeks (Cycle 2, Day 78 and Cycle 3, Day 120). Pre-treatment with an i.v. bolus of cyclophosphamide (CPO) will be given 1 to 3 days before the first administration of ONCOS-102 (Cycle 1, Day 1) and before administration of Cycle 2 of ONCOS-102 (Day 78). Patients will also receive pemetrexed/cisplatin (carboplatin) in 21-day cycles starting on Day 22 and continuing as applicable during the study period of 6 cycles of pemetrexed/cisplatin (carboplatin) in combination with ONCOS-102.
Arm Title
Pemetrexed/cisplatin (carboplatin)
Arm Type
Active Comparator
Arm Description
Patients will be treated with pemetrexed/cisplatin (carboplatin) in 21-day cycles starting on Day 1, and continuing as applicable during the study period of 6 cycles of chemotherapy. Patients will be monitored regularly for immunological assessment (PBMCs) including Month 9 and Month 12 (i.e., after the end of study visit), and will be followed up for survival every 3 months until end of life.
Intervention Type
Biological
Intervention Name(s)
ONCOS-102
Intervention Type
Drug
Intervention Name(s)
Pemetrexed/cisplatin (carboplatin)
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Primary Outcome Measure Information:
Title
Number of patients with any (Serious and Non-Serious) Adverse Event measured to assess safety and tolerability
Time Frame
6 months
Secondary Outcome Measure Information:
Title
To determine and compare tumour-specific immunological activation in the peripheral blood in the experimental group and the control group. Number of patients in the respective arms with induction of Tumor specific CD8+ T Cells in PBMC
Time Frame
6 months
Title
To determine and compare immunological activation in tumour mass in the experimental group and the control Group. Number of patients in the respective arms with infiltration of CD8+ T Cells into tumours
Time Frame
6 months
Title
To determine and compare overall response rate in the experimental group and the control group by number of patients with PD, SD, PR and CR in the respective arms
Time Frame
6 months
Title
To determine and compare progression-free survival (PFS) in the experimental group and the control group by median time to progression in the respective arms
Time Frame
6 months
Title
To determine and compare overall survival (OS) in the experimental group and the control group
Time Frame
Until death
Title
To analyse immunological activation by comparing patients with and without presence of tumour antigen recognizing CD8+ T cells
Time Frame
6 months
Title
To analyse clinical outcome by time to event endpoints (OS and PFS)
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent. Male or female, ≥18 years of age. Histologically confirmed unresectable (advanced) malignant pleural mesothelioma in patients who are not candidates for curative surgery and for whom therapy with pemetrexed in combination with cisplatin or carboplatin is considered appropriate. This include: patients who are naïve to chemotherapy, and those who have already received pemetrexed in combination with cisplatin or carboplatin to which their tumour initially responded, but they have relapsed after at least 6 months. The patient may be evaluated by a multidisciplinary consultation (according to hospital procedure), however the final decision about the inclusion of a patient is made by the principal investigator. Measurable disease according to Response Evaluation in Solid Tumour (RECIST 1.1). Tumour must be accessible to intratumoural (i.t.) injections and to tumour core needle biopsy or thoracoscopy for tissue sampling and immunohistochemistry analysis. The patients must be eligible to receive the study specific chemotherapies, including cyclophosphamide, according to the SPCs and local practice. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance score 0 to 1. Acceptable liver, renal, and haematological functions. All women of childbearing potential must have a negative urine or serum pregnancy test at screening and all patients must agree to use barrier contraception (i.e. condom) during study treatment and for 2 months after the last virus treatment, 6 months after the last dose of pemetrexed/cisplatin/carboplatin and 12 months after the dose of cyclophosphamide. Exclusion Criteria: Receipt of oncolytic virus treatment, or vaccination with a vaccine containing live virus within 4 weeks before Day 1. Use of significant immunosuppressive medication, including high dose corticosteroid (defined as the equivalent of >10 mg/day prednisone) within 4 weeks before Day 1. Patients who participated in a study with an investigational drug or device within 4 weeks prior to Day 1. Active bacterial, viral, or fungal infections, requiring systemic therapy. Severe arrhythmia, heart failure, previous cardiac infarction, or acute inflammatory heart disease. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient, if included in this study. Known infection with HIV, hepatitis B, or hepatitis C. Known brain metastases. History of organ transplant. Females who are pregnant or breast feeding. Unwillingness or inability to comply with the study protocol for any reason. Patients with pre-existing hearing loss or neuropathy that may worsen due to potential neurotoxicity from cisplatin. Patients with a history of hypersensitivity to cisplatin or carboplatin or pemetrexed or cyclophosphamide (or any of its metabolites). Patients who are taking phenytoin for prophylactic use. History of malignant tumour, unless the patient has been without evidence of disease for at least 3 years, or the tumour was a non-melanoma skin tumour, cervical carcinoma in situ, or prostatic carcinoma in situ.
Facility Information:
Facility Name
Centre Georges-François Leclerc
City
Dijon
Country
France
Facility Name
CHU de Rennes - Pontchaillou
City
Rennes
Country
France
Facility Name
Hospital Universitario Quirón
City
Barcelona
Country
Spain
Facility Name
Vall d'Hebron Univerity Hospital
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari de Girona Doctor Josep Trueta - Institut Català d'Oncologia
City
Girona
Country
Spain
Facility Name
Hospital 12 de octubre
City
Madrid
Country
Spain
Facility Name
Hospital Universitario HM Sanchinarro
City
Madrid
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

A Randomised Phase II Open-label Study With a Phase Ib Safety lead-in Cohort of ONCOS-102, an Immune-priming GM-CSF Coding Oncolytic Adenovirus, and Pemetrexed/Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma

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