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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

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ClinicalTrials.gov Identifier: NCT02879669
Recruitment Status : Recruiting
First Posted : August 26, 2016
Last Update Posted : September 18, 2018
Sponsor:
Collaborator:
Theradex
Information provided by (Responsible Party):
Targovax ASA ( Targovax Oy )

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. The trial's main objectives are determination of safety, immune activation, clinical response and the correlation between clinical outcome and the immunological data.

Condition or disease Intervention/treatment Phase
To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With Chemotherapy Biological: ONCOS-102 Drug: Pemetrexed/cisplatin (carboplatin) Drug: Cyclophosphamide Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : June 2016
Estimated Primary Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Experimental: ONCOS-102+cyclophosphamide+pemetrexed/cisplatin
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 in 21-day cycles starting on Day 22 and continuing as applicable during the study period of 6 cycles of pemetrexed/cisplatin in combination with ONCOS-102.
Biological: ONCOS-102
Drug: Pemetrexed/cisplatin (carboplatin)
Drug: Cyclophosphamide
Other Name: cisplatin

Active Comparator: Pemetrexed/cisplatin
Patients will be treated with pemetrexed/cisplatin 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.
Drug: Pemetrexed/cisplatin (carboplatin)



Primary Outcome Measures :
  1. Number of patients with any (Serious and Non-Serious) Adverse Event measured to assess safety and tolerability [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. To determine and compare overall survival (OS) in the experimental group and the control group [ Time Frame: Until death ]
  6. To analyse immunological activation by comparing patients with and without presence of tumour antigen recognizing CD8+ T cells [ Time Frame: 6 months ]
  7. To analyse clinical outcome by time to event endpoints (OS and PFS) [ Time Frame: 6 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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/cisplatin (and carboplatin in case of toxicity to cisplatin during treatment) is considered appropriate.

    • This includes patients who are naïve to chemotherapy,
    • and those who have already received pemetrexed/cisplatin 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 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02879669


Contacts
Contact: Sylvia Vetrhus, MSc.Pharm +4792201571 sylvia@targovax.com
Contact: Magnus Jäderberg, MD +447791443820 magnus.jaderberg@targovax.com

Locations
France
Centre Georges-François Leclerc Recruiting
Dijon, France
Contact: Nicolas Isambert, MD         
Spain
Hospital Universitario Quirón Recruiting
Barcelona, Spain
Contact: Santiago Viteri         
Hospital Universitari de Girona Doctor Josep Trueta - Institut Català d'Oncologia Recruiting
Girona, Spain
Contact: Joaquim Bosch         
Hospital 12 de octubre Recruiting
Madrid, Spain
Contact: Luis Paz-Ares, MD         
Hospital Universitario HM Sanchinarro Recruiting
Madrid, Spain
Contact: Javier de Castro, MD         
Sponsors and Collaborators
Targovax Oy
Theradex

Responsible Party: Targovax Oy
ClinicalTrials.gov Identifier: NCT02879669     History of Changes
Other Study ID Numbers: ONCOS C719
2015-005143-13 ( EudraCT Number )
First Posted: August 26, 2016    Key Record Dates
Last Update Posted: September 18, 2018
Last Verified: September 2018

Additional relevant MeSH terms:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Cisplatin
Cyclophosphamide
Carboplatin
Pemetrexed
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors