Prostvac in Patients With Biochemically Recurrent Prostate Cancer

• ClinicalTrials.gov Identifier: NCT02649439
• Recruitment Status: Completed
• First Posted: January 7, 2016
• Results First Posted: July 6, 2021
• Last Update Posted: November 14, 2022
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Ravi A. Madan, M.D., National Cancer Institute (NCI)

Study Description

Brief Summary:

Background:

Some people who have been treated for prostate cancer still have high prostate-specific antigen (PSA) levels. This may indicate cancer. These people have non-metastatic castration sensitive prostate cancer (nmCSPC) or biochemical recurrent prostate cancer. Researchers think the immune system can be taught to fight and kill cancer cells. They think an immunotherapy vaccine called prostvac could help reduce PSA levels in people with this type of prostate cancer.

Objective:

To test if prostvac can decrease tumor growth rate as measured by PSA compared to getting surveillance alone.

Eligibility:

Men ages 18 or older who have nmCSPC or biochemical recurrent prostate cancer

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Bone scan

Computed tomography (CT) scan, or magnetic resonance imaging (MRI) and positron emission tomography (PET) scan: They lie in a machine that takes pictures of the body.

Electrocardiogram: Soft electrodes are stuck to the skin to record heart signals.

Participants will be part of 1 of 2 arms: Arm A will get prostvac for 6 months. Arm B will have surveillance for 6 months followed by prostvac for 6 months.

During the prostvac period, participants will get prostvac as a shot under the skin on weeks 1, 3, and 5, and then monthly for a total of 5 months.

Participants will have follow-up visits at least every month until they recover from prostvac side effects or their cancer worsens. Visits may include repeats of screening tests.

Participants will be followed for up to 15 years. They will have a physical exam every year for the first 5 years. They will have phone calls once a year.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Biological: PROSTVAC -V; Biological: PROSTVAC-F	Phase 2

Detailed Description:

BACKGROUND

• Androgen deprivation therapy (ADT) and surveillance are treatment options for prostate cancer patients with biochemical progression after localized therapy (biochemically recurrent prostate cancer). The primary goal in these patients is to prevent morbidity from their cancer and to do so with limited toxicity.
• Prostvac (Prostvac; developed by the National Cancer Institute [NCI] and licensed to BN Immunotherapeutics, Mountain View, CA) is a novel candidate prostate cancer immunotherapy for the treatment of prostate cancer. It is a viral vector based therapeutic cancer vaccine that is administered via subcutaneous injections. In a randomized controlled Phase 2 trial, Prostvac therapy was associated with a prolongation of survival in men with metastatic castrate-resistant prostate cancer. A phase III trial recently completed accrual of patients in this same population.
• There is also rationale to use therapeutic cancer vaccines such as Prostvac in earlier stage prostate cancer patients to maximize the potential therapeutic effect of immune stimulating therapy.
• Analysis of previous trials using therapeutic cancer vaccines alone suggests that such therapies may alter tumor growth rate.

OBJECTIVE

Primary Objective:

-Determine if the therapeutic cancer vaccine prostvac can decrease tumor growth rate as measured by prostate-specific antigen (PSA) rise after 6 months compared to a group getting surveillance alone.

KEY ELIGIBILITY CRITERIA

• Histologically confirmed adenocarcinoma of the prostate
• Patients with negative computed tomography (CT) Scan and Tc-99m Bone Scan
• Patients with a PSA over 0.8 ng/ml for patients following radical prostatectomy or for patients following definitive radiation therapy: a rise in PSA of greater than or equal to 2 ng/mL above the nadir
• Patients with a PSA doubling time of 5-15 months
• No history of active autoimmune disease or history of organ compromising autoimmune disease
• Eastern Cooperative Oncology Group (ECOG) 0 -1

DESIGN

• Randomized study

• Accrual goal is 36 evaluable patients per arm; randomized 1:1 to:

  • Arm A: Prostvac for 6 months with an additional optional year of maintenance for eligible patients OR
  • Arm B: Surveillance for 6 months, then Prostvac for 6 months with an additional year of maintenance for eligible patients

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prostvac in Patients With Biochemically Recurrent Prostate Cancer
• Actual Study Start Date: December 22, 2015
• Actual Primary Completion Date: March 28, 2019
• Actual Study Completion Date: October 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: A/PROSTVAC treatment; PROSTVAC treatment for 6 months with an additional optional year of maintenance for eligible patients	Biological: PROSTVAC -V; Recombinant Vaccinia Virus Vector Vaccine of the Genus Orthopoxvirus; Biological: PROSTVAC-F; Recombinant Fowlpox Virus Vector Vaccine of the Genus Avipoxvirus
Experimental: B/ Delayed PROSTVAC treatment; Surveillance for 6 months followed by PROSTVAC treatment for 6 months with an additional year of maintenance for eligible patients	Biological: PROSTVAC -V; Recombinant Vaccinia Virus Vector Vaccine of the Genus Orthopoxvirus; Biological: PROSTVAC-F; Recombinant Fowlpox Virus Vector Vaccine of the Genus Avipoxvirus

Outcome Measures

Primary Outcome Measures :

1. Tumor Growth Rate as Measured by Prostate-specific Antigen (PSA) Rise After 6 Months When PROSTVAC is Initiated Compared to a Group on Surveillance for 6 Months [ Time Frame: 6 months ]
   Tumor growth rate was measured using the equation PSA (log growth rate) +/- SE (standard error).

Secondary Outcome Measures :

1. Effects of Vaccine on Prostate-specific Antigen (PSA) Growth Rate When PROSTVAC is Initiated After 6 Months on Surveillance [ Time Frame: After the participants in the Arm/Group "B/ Delayed PROSTVAC Treatment" received treatment for 6 months after their 6 month surveillance (e.g., 12 months total). ]
   Tumor growth rate was measured using the equation PSA (log growth rate) +/- SE (standard error).
2. Number of Participants With Prostate-specific Antigen (PSA) Specific T-Cells at Baseline and 6 Months [ Time Frame: Baseline and 6 months ]
   Normal PSA is 0 nanograms per milliliter (ng/mL). Above 0 ng/mL is considered an increase in tumor growth.

Other Outcome Measures:

1. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) [ Time Frame: Date treatment consent signed to date off study, approximately 55 months and 13 days for Arm/Group A, and 57 months and 22 days for Arm/Group B. ]
   Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
2. Median Late Change in Peripheral Blood Mononuclear Cells (PBMCs) in Refined Subsets Monocyte Nonclassical, Monocyte Nonclassical Programmed Death Ligand 1 (PD-L1+), and Monocyte PD-1+ After PROSTVAC [ Time Frame: Day 29 (Post vaccination) vs Pre (Baseline) ]
   Blood samples collected were analyzed by multicolor flow cytometry in PBMCs for refined subsets of Monocytes. Changes in levels of PBMC subsets was a descriptive result with median percent change and interquartile range reported. P values were calculated using the Mann Whitney Test.
3. Median Late Change in Peripheral Blood Mononuclear Cells (PBMCs) in Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8), Regulatory T-cells (Treg), Natural Killer (NK), and Myeloid-derived Suppressor Cells (MDSC) After PROSTVAC [ Time Frame: Day 29 (Post vaccination) vs Pre (Baseline) ]
   Blood samples collected were analyzed by multicolor flow cytometry in PBMCs for cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), Natural Killer (NK), myeloid-derived suppressor cell (MDSC) and Tregs. P values were calculated using the Mann Whitney Test.
4. Peripheral Blood Mononuclear Cells (PBMCs) in Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8), Regulatory T-cells (Treg), Natural Killer (NK), and Myeloid-derived Suppressor Cells (MDSC), and naïve CD4 and CD8 T Cells After PROSTVAC [ Time Frame: Baseline (Day 1) and one month (Day 29) after vaccine or surveillance (in the Delayed PROSTVAC group) ]
   Blood samples collected were analyzed by multicolor flow cytometry in PBMCs for cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), Natural Killer (NK), myeloid-derived suppressor cell (MDSC), Tregs, and naïve CD4 and naïve CD8 T cells. P values were calculated using the Wilcoxon signed rank test.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

• INCLUSION CRITERIA:
• Histopathological documentation of prostate cancer confirmed in either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, Walter Reed National Military Medical Center, Memorial Sloan Kettering Cancer Center (MSKCC), Dana-Farber Cancer Institute (DFCI) or Beth Israel Deaconess Medical Center (BIDMC) prior to enrollment. If no pathologic specimen is available, patients may enroll with a pathologists report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.

• Biochemical progression after definitive radiation or surgery defined as follows:

  • For patients following definitive therapy: a rise in prostate-specific antigen (PSA) of greater than or equal to 2ng/mL above the nadir (per Radiation Therapy Oncology Group (RTOG)-American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria).
  • For patients following radical prostatectomy: rising PSA after surgical procedure. (Patients must have a PSA greater than or equal to 0.8 ng/ml)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 1 (Karnofsky greater than or equal to 80%).
• Patients must have a PSA doubling time of 5-15 months.
• Patients must have a rising PSA as confirmed by 3 values done at least 1 week apart and over no less than 1 month.
• Recovery from acute toxicity related to prior therapy, including surgery and radiation, or no toxicity greater than or equal to grade 2.
• Negative computed tomography (CT) scan/magnetic resonance imaging (MRI) and bone scan for metastatic prostate cancer.

• Hematological eligibility parameters (within 16 days before starting therapy)

  • Granulocyte count greater than or equal to 1000/mm^3
  • Platelet count greater than or equal to 100 000/mm^3
  • Hemoglobin (Hgb) greater than or equal to 10g/dL

• Biochemical eligibility parameters (within 16 days before starting therapy):

  --Hepatic function: bilirubin less than or equal to 1.5mg/dL (OR in patients with Gilbert's syndrome normal.

• No other active malignancies within the past 36 months (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder) or life-threatening illnesses, in the opinion of the investigator
• Willing to travel to the National Institutes of Health (NIH), MSKCC, DFCI, BIDMC for follow-up visits.
• 18 years of age or older.
• Able to understand and sign informed consent.
• Baseline testosterone greater than or equal to 100 ng/dl
• PSA less than or equal to 30 ng/mL.
• The effects PROSTVAC on the developing human fetus are unknown. For this reason, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study therapy and at least one month post therapy. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.

EXCLUSION CRITERIA:

• Immunocompromised status due to:

  • Human immunodeficiency virus (HIV) positivity.
  • Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed.
  • Other immunodeficiency diseases
  • Splenectomy
• Chronic administration (defined as daily or every other day for continued use > 14 days) of corticosteroids deemed systemic by investigator within 28 days before the first planned dose of PROSTVAC. Use of inhaled steroids, nasal sprays, intra-articular injections and topical creams for small body areas is allowed.
• Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with patient s ability to carry out the treatment program.
• Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (eg phytoestrogens and saw palmetto)
• History of prior chemotherapy
• History of prior immunotherapy within the last 3 years
• Major surgery within 4 weeks prior to enrollment (Day 1 visit).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to poxviral vaccines (e.g., vaccinia vaccine)
• Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin).
• History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis
• Previous serious adverse reactions to smallpox vaccination
• Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the Day 1 vaccination: Day 1 vaccination: (a) children less than or equal to 3 years of age, (b) pregnant or nursing women, (c) individuals with current or extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV.
• Receipt of an investigational agent within 28 days (or 56 days for an antibody-based therapy) before the first planned dose of study drugs.
• Patients who test positive for hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Uncontrolled hypertension (systolic blood pressure (SBP)>170/ DBP>105)
• Recruitment Strategies

This study will be listed on available websites (www.clinicaltrials.gov,

https://ccr.cancer.gov/clinical-trials-search-start) and participants will be recruited from the current patient population at NIH.

Contacts and Locations

Locations

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02115

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10021

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ravi A Madan, M.D.; National Cancer Institute (NCI)

  Study Documents (Full-Text)

Documents provided by Ravi A. Madan, M.D., National Cancer Institute (NCI):

Study Protocol and Statistical Analysis Plan  [PDF] May 30, 2018

Informed Consent Form  [PDF] June 12, 2018

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

• Responsible Party: Ravi A. Madan, M.D., Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02649439
• Other Study ID Numbers: 160035; 16-C-0035
• First Posted: January 7, 2016
• Results First Posted: July 6, 2021
• Last Update Posted: November 14, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ravi A. Madan, M.D., National Cancer Institute (NCI):

Vaccine; PSA; Surveillance; Immunotherapy

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases