Randomized Controlled Trial of ProstAtak® Immunotherapy During Active Surveillance for Prostate Cancer (ULYSSES)

Sponsor

Candel Therapeutics, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02768363

Collaborator

(none)

187

Enrollment

Locations

Arms

8.1

Patients Per Site

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness of ProstAtak® immunotherapy in patients undergoing active surveillance for localized prostate cancer. ProstAtak® involves the use of aglatimagene besadenovec (CAN-2409) to kill tumor cells and stimulate 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 been well tolerated in previous trials in patients with prostate cancer and other tumor types. Biochemical, pathologic and immune responses have been demonstrated in newly diagnosed and recurrent prostate cancer. 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 of care active surveillance evaluations.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Biological: aglatimagene besadenovec Biological: placebo Drug: valacyclovir	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

187 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized Controlled Trial Of AdV-tk + Valacyclovir Administered During Active Surveillance For Newly Diagnosed Prostate Cancer

Study Start Date :

May 1, 2016

Anticipated Primary Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ProstAtak® Patients randomized to the ProstAtak arm will receive two courses of aglatimagene besadenovec (CAN-2409) + valacyclovir	Biological: aglatimagene besadenovec Aglatimagene besadenovec will be delivered to the prostate via trans-rectal ultrasound guided injection followed by 14 days of oral prodrug, valacyclovir. The second aglatimagene besadenovec injection will be 2-3 weeks after the first followed by 14 days of valacyclovir. Other Names: AdV-tk CAN-2409 Drug: valacyclovir Oral prodrug to be given for 14 days starting the day after each aglatimagene besadenovec or placebo injection.
Placebo Comparator: Placebo Patients randomized to the placebo arm will receive two corresponding courses of placebo + valacyclovir	Biological: placebo Placebo will be delivered to the prostate via trans-rectal ultrasound guided injection followed by 14 days of oral prodrug, valacyclovir. The second placebo injection will be 2-3 weeks after the first followed by 14 days of valacyclovir. Drug: valacyclovir Oral prodrug to be given for 14 days starting the day after each aglatimagene besadenovec or placebo injection.

Arm

Intervention/Treatment

Active Comparator: ProstAtak®

Patients randomized to the ProstAtak arm will receive two courses of aglatimagene besadenovec (CAN-2409) + valacyclovir

Biological: aglatimagene besadenovec

Aglatimagene besadenovec will be delivered to the prostate via trans-rectal ultrasound guided injection followed by 14 days of oral prodrug, valacyclovir. The second aglatimagene besadenovec injection will be 2-3 weeks after the first followed by 14 days of valacyclovir.

Other Names:

AdV-tk

CAN-2409

Drug: valacyclovir

Oral prodrug to be given for 14 days starting the day after each aglatimagene besadenovec or placebo injection.

Placebo Comparator: Placebo

Patients randomized to the placebo arm will receive two corresponding courses of placebo + valacyclovir

Biological: placebo

Placebo will be delivered to the prostate via trans-rectal ultrasound guided injection followed by 14 days of oral prodrug, valacyclovir. The second placebo injection will be 2-3 weeks after the first followed by 14 days of valacyclovir.

Drug: valacyclovir

Oral prodrug to be given for 14 days starting the day after each aglatimagene besadenovec or placebo injection.

Outcome Measures

Primary Outcome Measures

Progression-free survival [Once all subjects have completed at least 3 years following randomization]

Secondary Outcome Measures

Biochemical response (change in PSA) [Assessed at each visit at 3, 6, 9 and 12 months then at least yearly]
Patient reported Health Related Quality of Life [Assessed at each visit at 3, 6, 9 and 12 months]
Time to radical treatment [5 years]
The safety profile will be characterized by collection of adverse event information and laboratory values during the treatment phase. [Assessed at each visit at 3, 6, 9 and 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria include:

Histologically confirmed adenocarcinoma of the prostate
Patients choosing active surveillance
Patients meeting definition of NCCN low risk, intermediate risk OR patients having only one NCCN high-risk feature
NCCN Low Risk is defined as having all of the following: PSA < 10 ng/ml, Gleason ≤ 6, T1-T2a
NCCN Intermediate Risk is defined as having at least one of the following and no high risk features: 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: High risk with more than 1 high risk factor; Locally advanced/very high risk=T3b-T4; Metastatic: N1 or M1
Patients must be planning and medically able to tolerate multiple transrectal ultrasound guided injections.
ECOG Performance status 0-2

Exclusion Criteria include:

Active liver disease, including known cirrhosis or active hepatitis
Patients on systemic corticosteroids (>10 mg prednisone per day) or other immunosuppressive drugs
Known HIV+ patients
Regional lymph node involvement or distant metastases
Other current malignancy (except squamous or basal cell skin cancers)
Other serious co-morbid illness or compromised organ function that, in the opinion of the investigator, would interfere with treatment or follow up
Prior treatment for prostate cancer except TURP. If prior TURP, patients must be deemed able to receive prostate biopsy and multiple intra-prostatic injections by the investigator
Patients taking 5-alpha-reductase inhibitors (e.g. finasteride, dutasteride)
Patients who had or plan to use ADT or have history of an orchiectomy.
Patients who are planning to undergo radical treatment for prostate cancer within 12 months.
Known sensitivity or allergic reactions to acyclovir or valacyclovir

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Foothills Urology	Golden	Colorado	United States	80401
2	Jesse Brown VA Medical Center	Chicago	Illinois	United States	60612
3	The University of Chicago	Chicago	Illinois	United States	60637
4	Southeast Louisiana Veterans Health Care System	New Orleans	Louisiana	United States	70119
5	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889
6	Kansas City VA Medical Center	Kansas City	Missouri	United States	64128
7	Sierra Nevada Health Care System VA	Reno	Nevada	United States	89502
8	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
9	Advanced Radiation Centers of New York (Integrated Medical Professionals)	North Hills	New York	United States	11042
10	Associated Medical Professionals of NY, PLLC	Syracuse	New York	United States	13210
11	Southwest Urology, Clinical Research Solutions	Middleburg Heights	Ohio	United States	44130
12	Oklahoma City VA Healthcare System	Oklahoma City	Oklahoma	United States	73104
13	VA Portland Health Care System	Portland	Oregon	United States	97239
14	Oregon Urology Insitute	Springfield	Oregon	United States	97477
15	Lancaster Urology	Lancaster	Pennsylvania	United States	17604
16	Allegheny Health Network-Triangle Urological Group	Pittsburgh	Pennsylvania	United States	15212
17	Ralph H. Johnson Veterans Affairs Medical Center	Charleston	South Carolina	United States	29401
18	San Antonio VA Healthcare System	San Antonio	Texas	United States	78229-4404
19	Woodland Center	The Woodlands	Texas	United States	77384
20	Texas Urology Specialists	Tomball	Texas	United States	77375
21	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia	United States	23249
22	Salem VA Medical Center	Salem	Virginia	United States	24153
23	Instituto Nacional de Ciencias Medicas y Nutrición, Salvador Subirán	Mexico City		Mexico