A Phase I/II, Safety Clinical Trial of DCVAC/PCa and ONCOS-102 in Men With Metastatic Castration-resistant Prostate Cancer

Study Overview
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Brief Summary
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This clinical trial is to evaluate the safety of the combination of DCVAC/PCa with ONCOS-102 in men with castration-resistant advanced metastatic prostate cancer, who have progressed following initial therapy with either hormones (e.g. abiraterone and enzalutamide) or chemotherapy. Male patients with castration-resistant advanced metastatic prostate cancer, who have progressed following initial therapy with either All patients must have at least one readily accessible soft tissue/nodal tumor lesion (for intra-tumoral application of ONCOS-102 and biopsy.

Detailed Description
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Study Description: All patients who fulfill all eligibility criteria will undergo a leukapheresis procedure. ONCOS-102 administration will start within 3 weeks of leukapheresis at Week 5 (35 days since baseline +/- 2 days), and 3 further doses will be administered on a weekly basis Cyclophosphamide A priming bolus dose of CPO (300 mg/m2 intravenously) will be given 1-3 days before the first (Week 5) and the fifth (Week 14) of ONCOS-102 administration. DCVAC/PCa therapy will start 6 weeks after leukapheresis at Week 8. DCVAC/PCa will be administered subcutaneously in cycles, always on Day 1 (+/- 3 days) of the corresponding cycle.

Official Title
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A Phase I/II, Clinical Trial to Evaluate the Safety and Immune Activation of the Combination of DCVAC/PCa, and ONCOS-102, in Men With Advanced Metastatic Castration-resistant Prostate Cancer.

Conditions
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Castration-resistant Prostate Cancer

Intervention / Treatment
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* Biological: DCVac/PCa
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate Radiographically documented metastatic disease with evidence of disease progression Laboratory parameters per protocol Surgically or medically castrate Patients who have progressed following: a. at least initial therapy (chemotherapy or treatment with a hormonal agent known to impact survival such as abiraterone and enzalutamide); or b. one first-line chemotherapy regimen and one additional hormonal agent known to impact survival such as abiraterone and enzalutamide; or c. failure of two lines of chemotherapy; or d. failure of pre-chemotherapy abiraterone or enzalutamide and subsequent chemotherapy Exclusion Criteria: Patients with neuroendocrine or small cell cancer of the prostate 2. History of other malignant disease (with the exception of the primary prostate cancer and non-melanoma skin tumors) in the past 5 years Pre-defined co-morbidities Administration of experimental therapy within the last 4 weeks before start of screening Treatment with immunotherapy within the last 3 months before start of screening Treatment with radiopharmaceutical drugs within 8 weeks before start of screening Receipt of oncolytic virus treatment or vaccination with a live virus within 4 weeks of study start History of organ transplantation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label combination treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DCVac and ONCOS-102<br>ONCOS-102 is given intra-tumor up to 4 times, cyclophosphamide is given prior to the first dose of ONCOS-102 and at the fifth week of treatment DCVac is given sc every 21-28 days for up to 10 doses | Biological: DCVac/PCa<br>* Oncolytic adenovirus containing immunostimulatory cytokine granulocyte-monocyte colony-stimulating factor (GM-CSF). This is an experimental therapy. DCVac/Pca consists of activated autologous dendritic cells. This is an experimental therapy.<br>* Other names: ONCOS-102;Drug: Cyclophosphamide<br>* immunomodulatory medication given around the ONCOS-102 dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | PFS measured by modifications to the RECIST 1.1. PFS is defined as the time from the first dose of SoC therapy administered to tumor progression or death from any cause. | 96 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Defined as the time from Baseline visit to the date of death for any cause | 96 months | 
| Safety | Reports of adverse events, serious adverse events, lab abnormalities utilizing NCI CTCAE v.4.033 | 96 months | 
| Time to Progression-PSA | demonstrated by rising PSA as defined by the Prostate Cancer Workging Group2 | 96 months | 
| Radiographic Progression- free survival | composite assessment of progression of bone lesions, soft-tissue lesions or death due to any cause | 96 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Castrate-resistant