To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With ChemotherapyPhase 1/2NCT02879669
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
A Phase 1/2 study testing ONCOS-102, Pemetrexed/cisplatin (carboplatin) and Cyclophosphamide in people with To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With Chemotherapy, run by Targovax Oy at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With Chemotherapy
- What is being tested?
- ONCOS-102, Pemetrexed/cisplatin (carboplatin) and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Jun 2016to 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
- 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.
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Spain5 sites
Hospital Universitario Quirón
Barcelona
Vall d'Hebron Univerity Hospital
Barcelona
Hospital Universitari de Girona Doctor Josep Trueta - Institut Català d'Oncologia
Girona
Hospital 12 de octubre
Madrid
Hospital Universitario HM Sanchinarro
Madrid
France2 sites
Centre Georges-François Leclerc
Dijon
CHU de Rennes - Pontchaillou
Rennes
About this study
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.
- Conditions
- To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With Chemotherapy
- Being tested
- ONCOS-102, Pemetrexed/cisplatin (carboplatin), Cyclophosphamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ONCOS-102Biological
Pemetrexed/cisplatin (carboplatin)Drug
CyclophosphamideDrug
| Study group | Role | What they receive |
|---|---|---|
| ONCOS-102+cyclophosphamide+pemetrexed/cisplatin (carboplatin) | Experimental | 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. Receives: Biological: ONCOS-102; Drug: Pemetrexed/cisplatin (carboplatin); Drug: Cyclophosphamide |
| Pemetrexed/cisplatin (carboplatin) | Active comparator | 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. Receives: Drug: Pemetrexed/cisplatin (carboplatin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with any (Serious and Non-Serious) Adverse Event measured to assess safety and tolerability
Measured: 6 months
Secondary outcomes (7)
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
Measured: 6 months
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
Measured: 6 months
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
Measured: 6 months
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
Measured: 6 months
To determine and compare overall survival (OS) in the experimental group and the control group
Measured: Until death
To analyse immunological activation by comparing patients with and without presence of tumour antigen recognizing CD8+ T cells
Measured: 6 months
To analyse clinical outcome by time to event endpoints (OS and PFS)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2016 (estimated)
- Study startJun 2016
- Primary completionMay 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With ChemotherapyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Targovax Oy
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Theradex
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02879669
- Sponsor's protocol ID
- ONCOS C719
- Other IDs
- 2015-005143-13, 2015
- Status last verified
- Oct 2020
- First submitted
- 13 Jul 2016
- Last updated
- 8 Oct 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02879669
- Acronym / sponsor ID
- ONCOS C719
- Conditions
- To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With Chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Targovax OyIndustry (pharma, biotech, devices)
- Collaborators
- Theradex
- Study start
- Jun 2016
- Primary completion
- May 2020 (actual)
- First posted
- 26 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ONCOS-102+cyclophosphamide+pemetrexed/cisplatin (carboplatin) | Experimental | Biological: ONCOS-102, Drug: Pemetrexed/cisplatin (carboplatin), Drug: CyclophosphamideONCOS-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. |
| Pemetrexed/cisplatin (carboplatin) | Active comparator | Drug: Pemetrexed/cisplatin (carboplatin)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- 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).
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ONCOS-102 | Biological | ONCOS-102+cyclophosphamide+pemetrexed/cisplatin (carboplatin) |
| Pemetrexed/cisplatin (carboplatin) | Drug | ONCOS-102+cyclophosphamide+pemetrexed/cisplatin (carboplatin), Pemetrexed/cisplatin (carboplatin) |
| Cyclophosphamide | Drug | ONCOS-102+cyclophosphamide+pemetrexed/cisplatin (carboplatin) |
Primary outcome
Number of patients with any (Serious and Non-Serious) Adverse Event measured to assess safety and tolerability
Time frame: 6 months
7 secondary outcomes
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
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
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
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
To determine and compare overall survival (OS) in the experimental group and the control group
Time frame: Until death
To analyse immunological activation by comparing patients with and without presence of tumour antigen recognizing CD8+ T cells
Time frame: 6 months
To analyse clinical outcome by time to event endpoints (OS and PFS)
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ONCOS-102, Pemetrexed/cisplatin (carboplatin) and Cyclophosphamide in people with To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With Chemotherapy, run by Targovax Oy at 7 sites in 2 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 12 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Spain, France. 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?
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?
Number of patients with any (Serious and Non-Serious) Adverse Event measured to assess safety and tolerability (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Oct 2020.