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)

Bavarian Nordic

Status and phase: Completed; Phase 3

Conditions: Prostate Cancer Metastatic

Treatments: Drug: GM-CSF; Biological: PROSTVAC-F; Biological: Placebo; Biological: PROSTVAC-V; Other: GM-CSF Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01322490

BNIT-PRV-301

Details and patient eligibility

About

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.

Full 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

Enrollment: 1,297 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,297 participants in 3 patient groups, including a placebo group

PROSTVAC-V/F-TRICOM + GM-CSF

Experimental group

Description:

* PROSTVAC-V-TRICOM * PROSTVAC-F-TRICOM * GM-CSF

Treatment:

Biological: PROSTVAC-V

Biological: PROSTVAC-F

Drug: GM-CSF

PROSTVAC-V/F-TRICOM + GM-CSF placebo

Experimental group

Description:

* PROSTVAC-V-TRICOM * PROSTVAC-F-TRICOM * GM-CSF placebo

Treatment:

Biological: PROSTVAC-V

Biological: PROSTVAC-F

Other: GM-CSF Placebo

Placebo Control

Placebo Comparator group

Description:

PROSTVAC V/F Placebo + GM-CSF Placebo

Treatment:

Other: GM-CSF Placebo

Biological: Placebo