E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Asymptomatic or Minimally Symptomatic Metastatic, Castrate-Resistant Prostate Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Prostate Cancer in men who experience few or no symptoms and do not respond to treatment with hormones. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To ascertain whether the survival of subjects randomized to Arm V+G (PROSTVAC-V/F plus GM-CSF) or to Arm V (PROSTVAC-V/F) is superior to that from subjects randomized to Arm P (placebo control).
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E.2.2 | Secondary objectives of the trial |
To ascertain whether a greater proportion of subjects randomized to Arm V+G or to Arm V remain event-free at six months (or early termination) as compared to the subjects randomized to Arm P. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed Informed Consent 2. Men, ≥18 years of age with documented asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. 3. Castrate testosterone level < 50 ng/dl 4. 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). a. Radiological progression defined as any new/enlarging bone mestatases or new/enlarging lymph node disease, consistent with prostate cancer. OR b. 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). 5. Chemotherapy naïve. No prior chemotherapy for metastatic prostate cancer. Neo-adjuvant or adjuvant chemotherapy for primary prostate cancer is permissible if >3 years prior. 6. Vaccinia-experienced (previous smallpox vaccination). 7. ECOG Performance Score of 0 or 1. 8. Life expectancy ≥ 1 year. 9. Bone Marrow function: - Absolute neutrophil count ≥ 1,500/mm3 - Hemoglobin ≥ 10 g/dL - Platelet count ≥ 100,000/mm3 10. Hepatic Function: - AST and ALT ≤ 2.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN 11. Renal Function: - Creatinine ≤ 2.0 times ULN 12. Currently using a GnRH agonist or antagonist (unless surgically castrated) |
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E.4 | Principal exclusion criteria |
1. Cancer-related pain requiring scheduled opioid narcotics for control (as needed. ≤ 2x per week is allowed). 2. Metastasis to organ systems other than lymph nodes and/or bone. 3. LDH ≥ 2 times ULN. 4. Alkaline phosphatase ≥ 2 times ULN. 5. Estimated PSA doubling time of <1 month as established within 6 months of the anticipated first dose of vaccine or placebo. A minimum of 3 PSA level determinations, at least 2 weeks apart (over a 6 month time period), are required for assessment. 6. Concurrent or prior Provenge (sipuleucel-T) immunotherapy for prostate cancer 7. 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. There is no exclusion to previous experimental therapy provided dosing/treatment is completed at least 30 days prior to the first planned dose of vaccine unless otherwise noted. 8. History of prior malignancies other than prostate cancer within the past 3 years, excluding successfully resected basal or squamous cell carcinoma of the skin 9. 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). 10. Confirmed positive for HIV, hepatitis B, and /or hepatitis C. 11. Prior solid organ or bone marrow transplant 12. Immunodeficiency or splenectomy 13. Chronic immunosuppressive therapy within 30 days of screening. 14. Inflammatory eye disease requiring steroid treatment. 15. Chronic administration (defined as daily or every other day for continued use > 14 days) of systemic corticosteroids within 28 days of the first planned dose of PROSTVAC-V/F. Use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed. 16. History of or active autoimmune disease (e.g. autoimmune neutropenia, thrombocytopenia, or hemolytic anemia, systemic lupus erythematosis, Sjogren's syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, Addison's disease, Hashimoto's thyroiditis, or Graves disease). Persons with vitiligo are not excluded. Diabetics are not excluded if the condition is well controlled. 17. Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin), or GM-CSF. Subjects with a known or suspected allergy to radiological contrast agents are eligible, but this must be noted in the subject's medical history and in the chart notes. 18. History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis. 19. Previous adverse reactions to smallpox vaccination. 20. Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the Day 1 vaccination or until the vaccination site heals completely: (a) children ≤ 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV. 21. Any condition which, in the opinion of the investigator, would prevent full participation in this trial (including the Long-Term Follow- Up), or would interfere with the evaluation of the trial endpoints 22. Study personnel. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- the proportion of event-free subjects (radiological progression, pain progression, chemotherapy initiation, or death) at six months (or early termination) compared to placebo.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 97 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Chile |
Denmark |
Estonia |
France |
Germany |
Iceland |
Israel |
Netherlands |
Poland |
Puerto Rico |
Russian Federation |
Slovakia |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is defined as the last anticipated visit of the last patient enrolled. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |