Phase 3 Study of ProstAtak® Immunotherapy With Standard Radiation Therapy for Localized Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of ProstAtak® immunotherapy in combination with radiation therapy for patients with intermediate-high risk localized prostate cancer. ProstAtak kills tumor cells and stimulates a cancer vaccine effect. Killing tumor cells in an immune stimulatory environment induces the body's immune system to detect and destroy cancer cells. ProstAtak has shown synergy with radiation without added toxicity and lower than expected recurrence rates in previous clinical trials. The hypothesis is that ProstAtak can lead to improvement in the clinical outcome for patients with prostate cancer. Participants will be randomized to the ProstAtak or control arm at a 2:1 ratio. Both arms receive standard external beam radiation therapy. Short-term androgen deprivation therapy may be given but is not required.

Official Title
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A Randomized Controlled Trial of ProstAtak® as Adjuvant to Up-front Radiation Therapy For Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: Aglatimagene besadenovec + valacyclovir
* Biological: Placebo + valacyclovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria include: Localized prostate cancer meeting the NCCN criteria of Intermediate Risk or patients having only one NCCN high-risk feature NCCN Intermediate Risk is defined as having at least one of the following: PSA 10-20 ng/ml, Gleason score =7, T2b-T2c High Risk with a single high risk feature is defined as having only one of the following: PSA>20 ng/ml, Gleason score 8-10, or T3a Excluded are those in the following risk groups: Low risk; High risk with more than 1 high risk factor; Locally advanced/very high risk=T3b-T4; Metastatic: N1 or M1 Planning to undergo standard prostate-only external beam radiation therapy ECOG Performance Status 0-2 Exclusion Criteria include: Liver disease, including known cirrhosis or active hepatitis Patients on systemic corticosteroids (>10mg prednisone per day) or other immunosuppressive drugs Known HIV+ patients Regional lymph node involvement or distant metastases Patients planning to receive whole pelvic irradiation Prior treatment for prostate cancer, except TURP or ADT. For ADT, it may only be given for a maximum of 6 months Patients who had or plan to have orchiectomy as the form of hormonal ablation Known sensitivity or allergic reactions to acyclovir or valacyclovir

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ProstAtak®<br>Aglatimagene besadenovec (CAN-2409) + valacyclovir + radiation therapy +/- ADT | Biological: Aglatimagene besadenovec + valacyclovir<br>* Patients will receive three courses of ProstAtak® each consisting of aglatimagene besadenovec injection + oral valacyclovir. AdV-tk injection will be delivered to the prostate via trans-rectal ultrasound guided injection as follows: The first injection will be given at least 15 days and not more than 8 weeks before starting radiation. The second injection will be 0-3 days before initiation of radiation therapy. The third injection will be 15-22 days after the 2nd injection. The prodrug, valacyclovir, will be administered at a fixed dose for 14 days after each AdV-tk injection. Standard external beam radiation therapy will be delivered to the prostate. Short-term androgen deprivation therapy (maximum of 6 months) is optional but must be decided before enrollment to allow for stratification.<br>* Other names: CAN-2409;|
| Placebo Comparator: Control<br>Placebo + valacyclovir + radiation therapy +/- ADT | Biological: Placebo + valacyclovir<br>* Patients will receive three courses each consisting of placebo injection + oral valacyclovir. Placebo injection will be delivered to the prostate via trans-rectal ultrasound guided injection as follows: The first injection will be given at least 15 days and not more than 8 weeks before starting radiation. The second injection will be 0-3 days before initiation of radiation therapy. The third injection will be 15-22 days after the 2nd injection. The prodrug, valacyclovir, will be administered at a fixed dose for 14 days after each placebo injection. Standard external beam radiation therapy will be delivered to the prostate. Short-term androgen deprivation therapy (maximum of 6 months) is optional but must be decided before enrollment to allow for stratification.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival defined as the time from randomization until the date of the first failure event will be compared for the ProstAtak® arm versus the placebo control arm. The analyses will be based on the intent to treat population. |  | Assessed at each visit every 6 months through year 5 until event occurs. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate cancer specific survival and overall survival will be compared for the ProstAtak® arm versus the placebo control arm. |  | Assessed at each visit every 6 months through year 5 after which long-term follow up of general health status will continue yearly. | 
| PSA nadir will be compared for the ProstAtak® arm versus the placebo control arm. |  | Assessed at each visit every 6 months through year 5. | 
| Patient reported Health Related Quality of Life outcomes will be collected using the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. The change in QOL over time will be compared for the ProstAtak® arm versus the placebo control arm. |  | Assessed at baseline and at 3, 6, 12, 18 and 24 months after completion of radiation. | 
| The safety profile will be characterized by collection of adverse event information and laboratory values during the treatment phase (until the completion of radiation). Data on late effects will be collected after radiation completion. |  | Assessed at each visit and continuously throughout the study. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, cytotoxicity, tumor vaccine, prostate cancer, radiotherapy