A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer (Prospect)

• ClinicalTrials.gov Identifier: NCT01322490
• Recruitment Status: Completed
• First Posted: March 24, 2011
• Results First Posted: August 8, 2019
• Last Update Posted: September 4, 2019
• Sponsor: Bavarian Nordic
• Information provided by (Responsible Party): Bavarian Nordic

Tracking Information

• First Submitted Date: March 23, 2011
• First Posted Date: March 24, 2011
• Results First Submitted Date: July 16, 2019
• Results First Posted Date: August 8, 2019
• Last Update Posted Date: September 4, 2019
• Actual Study Start Date: November 28, 2011
• Actual Primary Completion Date: September 25, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 9, 2019)

Overall Survival [ Time Frame: Randomization through the date of death due to any cause. Subjects were followed up for approximately 6 years from the first subject randomized to the completion of the study. ]

The time between the date of randomization and the date of death due to any cause. Subjects who did not experience death or the competing events of "definite" loss to follow-up or withdrawal of consent were right censored at the date of last contact. OS was calculated using the formula: OS = Date of death/competing event/censoring - date of randomization + 1.

Original Primary Outcome Measures (submitted: March 23, 2011)

Overall survival [ Time Frame: Survival will be assessed over the life of the study or approximately 5 years. ]

Overall survival will be measured for all patients until the required number of events per comparison arm is reached (approximately 534 events per comparison arm).

Current Secondary Outcome Measures (submitted: August 9, 2019)

Number of Subjects Alive Without Event at 6 Months [ Time Frame: Randomization through Week 25/End of Treatment visit. ]

A binary assessment that was performed for the 6-months timepoint for the categories of radiographic progression, pain progression, initiation of chemotherapy or death. Subjects without an event prior to 6-months were evaluated at 6-months. Subjects without event by 6-months and were not evaluated at 6-months were assumed to have had an event and analyzed as such. Progression events were defined as: (1) Two new lesions on bone scan, new metastases on CT scans, or an increased size of nodal lesions per RECIST 1.1. Bone or CT scans occurring prior to calendar month 6 were used to determine radiographic progression. (2) Introduction of scheduled opioid narcotics for cancer-related pain control. (3) Initiation of chemotherapy for prostate cancer was assessed as collected on progression forms as well as in cancer treatment and concomitant medications logs. (4) Death.

Original Secondary Outcome Measures (submitted: March 23, 2011)

Proportion of event-free patients compared with placebo [ Time Frame: Events will be measured at baseline and 6 months ]

This endpoint will measure the proportion of patients receiving PROSTVAC with or without GM-CSF who remain event-free (radiological progression, pain progression, initiation of chemotherapy, or death) at 6 months compared to placebo.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer
• Official Title: A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer
• Brief Summary: The purpose of this study is to determine whether PROSTVAC alone or in combination with GM-CSF is effective in prolonging overall survival in men with few or no symptoms from metastatic, castrate-resistant prostate cancer.

Detailed Description

BNIT-PRV-301 is a randomized, placebo-controlled, multi-center, global Phase 3 efficacy trial of PROSTVAC in men with asymptomatic or minimally symptomatic, metastatic, castrate-resistant prostate cancer. It is a 3-arm study and will evaluate overall survival in two separate comparisons, PROSTVAC plus adjuvant dose GM-CSF versus controls, and PROSTVAC without GM-CSF versus controls.

Patients will be randomized with equal probability into one of three double-blind arms. The intended interventions for randomized patients are:

1. (Arm V+G) PROSTVAC-V/F plus adjuvant dose GM-CSF
2. (Arm V) PROSTVAC-V/F plus GM-CSF placebo
3. (Arm P) Double placebo

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Prostate Cancer Metastatic

Intervention

• Biological: PROSTVAC-V
• Biological: PROSTVAC-F
• Drug: GM-CSF
• Other: GM-CSF Placebo
• Biological: Placebo
  PROSTVAC V/F Placebo

Study Arms

• Experimental: PROSTVAC-V/F-TRICOM + GM-CSF
  • PROSTVAC-V-TRICOM
  • PROSTVAC-F-TRICOM
  • GM-CSF
  Interventions:

  • Biological: PROSTVAC-V
  • Biological: PROSTVAC-F
  • Drug: GM-CSF
• Experimental: PROSTVAC-V/F-TRICOM + GM-CSF placebo
  • PROSTVAC-V-TRICOM
  • PROSTVAC-F-TRICOM
  • GM-CSF placebo
  Interventions:

  • Biological: PROSTVAC-V
  • Biological: PROSTVAC-F
  • Other: GM-CSF Placebo
• Placebo Comparator: Placebo Control
  PROSTVAC V/F Placebo + GM-CSF Placebo
  Interventions:

  • Other: GM-CSF Placebo
  • Biological: Placebo

• Publications *: Gulley JL, Borre M, Vogelzang NJ, Ng S, Agarwal N, Parker CC, Pook DW, Rathenborg P, Flaig TW, Carles J, Saad F, Shore ND, Chen L, Heery CR, Gerritsen WR, Priou F, Langkilde NC, Novikov A, Kantoff PW. Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2019 May 1;37(13):1051-1061. doi: 10.1200/JCO.18.02031. Epub 2019 Feb 28.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 9, 2019): 1297
• Original Estimated Enrollment (submitted: March 23, 2011): 1200
• Actual Study Completion Date: December 15, 2017
• Actual Primary Completion Date: September 25, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Men, ≥18years of age with documented asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer.

Documented progressive disease post surgical castration or during androgen suppression therapy, or during complete androgen blockade therapy and withdrawal. Documented by either criterion a (Radiological progression), OR criterion b (PSA progression).

1. Radiological progression defined as any new/enlarging bone metastases or new/enlarging lymph node disease, consistent with prostate cancer.

   OR

2. PSA progression defined by sequence of rising values separated by > 1 week (2 separate increasing values) over a threshold minimum of 2.0 ng/ml. (PCWG2 PSA eligibility criteria).

Chemotherapy naïve and Vaccinia-experienced (previous smallpox vaccination). Currently using a GnRH agonist or antagonist (unless surgically castrated).

Exclusion Criteria:

Cancer-related pain requiring scheduled opioid narcotics for control (as needed, ≤ 2x per week is allowed).

Metastasis to organ systems other than lymph nodes and/or bone. Estimated PSA doubling time of <1 month as established within 6 months of the anticipated first dose of vaccine or placebo.

Concurrent or prior Provenge (sipuleucel-T) immunotherapy for prostate cancer. Receipt of an investigational agent within 30 days (or 60 days for an antibody-based therapy) of the first planned dose of PROSTVAC-V/F.

History of prior malignancies other than prostate cancer within the past 3 years, excluding successfully resected basal or squamous cell carcinoma of the skin.

Congestive heart failure (NYHA Class II, III, or IV), unstable angina, ventricular or hemodynamically significant atrial arrhythmia, or cardiovascular disease such as stroke or myocardial infarction (current or within the past 6 months) Confirmed positive for HIV, hepatitis B, and /or hepatitis C. Immunodeficiency or splenectomy. History of or active autoimmune disease, persons with vitiligo are not excluded. Diabetics are not excluded if the condition is well controlled.

History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Denmark, Estonia, France, Germany, Iceland, Israel, Netherlands, Poland, Puerto Rico, Russian Federation, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT01322490
• Other Study ID Numbers: BNIT-PRV-301
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bavarian Nordic
• Original Responsible Party: Wayne Godfrey, MD; VP Clinical Development, BN ImmunoTherapeutics, Inc.
• Current Study Sponsor: Bavarian Nordic
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: James L. Gulley, MD; National Cancer Institute (NCI)
• Principal Investigator: Philip Kantoff, MD; Dana-Farber Cancer Institute

• PRS Account: Bavarian Nordic
• Verification Date: August 2019