Docetaxel and PROSTVAC for Metastatic Castration-Sensitive Prostate Cancer
Study Details
Study Description
Brief Summary
Background:
Metastatic castrate-sensitive prostate cancer is cancer that has spread beyond the prostate area. It can be controlled by lowering the amount of testosterone in the body. This is called androgen deprivation therapy (ADT). The vaccine PROSTVAC might help the immune system kill cancer cells. Researchers want to add PROSTVAC and docetaxel chemotherapy to ADT. They think this may work better against prostate cancer than ADT alone.
Objective:
To test if adding PROSTVAC and docetaxel to ADT works better against prostate cancer than ADT alone.
Eligibility:
Men ages 18 years and over with metastatic castrate-sensitive prostate cancer
Design:
Participants will be screened with:
Physical exam
Medical history
Blood tests
Possible CT, MRI, or bone scan: Participants lie in a machine. The machine takes pictures of the body.
Electrocardiogram: Soft electrodes are stuck to the skin to record heart signals.
Participants will have 2 optional tumor biopsies during the study.
Participants will join 1 of 2 groups. Both groups will get:
ADT
Docetaxel by vein
Steroids by mouth or vein before each docetaxel infusion
PROSTVAC injection
Both groups first have ADT. One to 4 months after, they have:
Group A:
Docetaxel every 3 weeks for 6 cycles
PROSTVAC 3 weeks after the last infusion
Booster injections 2 weeks later and then every 3 weeks, for 6 boosters total
Group B:
PROSTVAC
Booster 2 weeks later
Docetaxel hours later
Docetaxel and the booster every 3 weeks for 6 cycles
Participants will have a visit 4-5 weeks after the last treatment. They will then have visits every 12 weeks.
Participants will be followed for up to 15 years. This includes physical exams every year for 5 years.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Background:
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A phase III trial demonstrated that combining docetaxel and androgen deprivation therapy (ADT) significantly improved survival (57.6 vs 44.0 months (HR=0.56, (0.44-0.70), p <0.0001) for men with metastatic castration sensitive prostate cancer (mCSPC).
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PROSTVAC (developed by the National Cancer Institute [NCI] and licensed to Bavarian Nordic Immunotherapeutics, Mountain View, CA) is a therapeutic cancer vaccine for prostate cancer.
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Preclinical and clinical studies support the potential synergy in the combination of docetaxel and PROSTVAC. The potential to combine docetaxel with vaccine in mCSPC could improve upon the survival advantage that has been previously seen.
Objectives:
Primary
-To determine if PROSTVAC combined with docetaxel is able to induce greater antigen spreading (i.e. a broader immune response) with greater associated response score compared to docetaxel alone after 19 weeks.
Key Eligibility Criteria:
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Must have castrate sensitive prostate cancer (rising PSA and testosterone over 100) or is within 134 days of starting ADT (Arm A or B) or within 28 days of start ADT (Arm C)
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Histopathological confirmation of prostate cancer
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Patients must have metastatic disease
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Patients must have a performance status of 0 to 2 according to the ECOG criteria
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Patients must have adequate bone marrow, hepatic, and renal function
Design
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This is a randomized trial of ADT followed by simultaneous docetaxel 75 mg/m(2) q3 weeks x 6 cycles + PROSTVAC q3 weeks x 6 cycles versus ADT followed by sequential docetaxel 75 mg/m(2) q3 weeks x 6 cycles followed by PROSTVAC q3 weeks x 6 cycles in men with newly diagnosed mCSPC.
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Patients who have not started ADT or who have been on ADT 28 days or fewer will be assigned to treatment with PROSTVAC for 4 - 6 injections followed by docetaxel 75 mg/m2 q3 weeks x 6 cycles.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A/Sequential docetaxel followed by PROSTVAC Standard ADT followed by sequential docetaxel + prostvac |
Biological: PROSTVAC-V
It is a recombinant vaccinia virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 2x10(8) infectious units.
Biological: PROSTVAC-F
It is a recombinant fowlpox virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 1x10(9) infectious units.
Drug: Docetaxel
It is commercially available. It will be administered at 75 mg/m(2) intravenously.
|
| Experimental: B/ Combined docetaxel with PROSTVAC Standard ADT followed by combined docetaxel + prostvac |
Biological: PROSTVAC-V
It is a recombinant vaccinia virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 2x10(8) infectious units.
Biological: PROSTVAC-F
It is a recombinant fowlpox virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 1x10(9) infectious units.
Drug: Docetaxel
It is commercially available. It will be administered at 75 mg/m(2) intravenously.
|
| Experimental: C/ PROSTVAC prior to docetaxel Standard ADT followed by prostvac, then docetaxel |
Biological: PROSTVAC-V
It is a recombinant vaccinia virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 2x10(8) infectious units.
Biological: PROSTVAC-F
It is a recombinant fowlpox virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 1x10(9) infectious units.
Drug: Docetaxel
It is commercially available. It will be administered at 75 mg/m(2) intravenously.
|
Outcome Measures
Primary Outcome Measures
- Determine if PROSTVAC combined with docetaxel is able to induce greater antigen spreading (i.e. a broader immune response) with greater associated response score compared to docetaxel alone after 19 weeks. [2 years]
Response/efficacy.
Secondary Outcome Measures
- Compare response scores between both arms [39 weeks and 1 year]
patient's response scores will be compared between the two arms at 39 weeks and 1 year
- evaluate immunologic response between the two groups [39 weeks and 1 year]
Evaluate antigen-specific immune responses T-cell responses using nonparametric methods
Eligibility Criteria
Criteria
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INCLUSION CRITERIA:
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Documented histopathological confirmation of prostate cancer-from a CLIA certified laboratory.
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Patients must have metastatic disease, defined as at least one lesion on bone scan or at least one lesion that are measurable per RECIST 1.1. (Patients who have metastatic disease by these criteria prior to ADT, but then have changes after ADT that diminish the size of these lesions or changes on bone scan are still eligible.)
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Patients must have a performance status of 0 to 2 according to the ECOG criteria
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Patients must have adequate bone marrow, hepatic, and renal function with:
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ANC greater than or equal to 1500/microL, without CSF support
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Platelets greater than or equal to 100,000/microL
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AST(SGOT) less than or equal to 2.5 times upper limit of normal (ULN);
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ALT(SGPT) less than or equal to 2.5 times upper limit of normal (ULN);
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Total serum bilirubin less than or equal to 1.5 times upper limit of normal (ULN), OR in patients with Gilbert s syndrome, a total bilirubin less than or equal to 3.0)
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Serum albumin greater than or equal to 2.8 g/dL
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Lipase < 2.0 times the upper limit of normal and no radiologic or clinical evidence of pancreatitis
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Creatinine less than or equal to 1.5 times institutional upper limits of normal
OR
Creatinine clearance of greater than or equal to 50 ml/min/1.73 m(2) for patients with creatinine levels above institutional normal by 24-hour urine.
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Willing to travel to the NIH for follow-up visits
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18 years of age or older.
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Able to understand and sign informed consent.
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May have had up to 24 months of ADT (testosterone suppression therapy in the nonmetastatic setting) and are at least 12 months removed from treatment
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Men treated or enrolled on this protocol must also agree to use adequate contraception, prior to the study, for the duration of study participation, and 4 months after completion. Sexually active subjects and their female partners must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must also agree to use both a barrier method and a second method of birth control during the course on the study and for 4 months after the last dose of study drug(s). 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.
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Must have started ADT for metastatic disease within 134 days (for Arm A and B) or within 28 days (for Arm C).
EXCLUSION CRITERIA:
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Immunocompromised status due to:
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Human immunodeficiency virus (HIV) positivity.
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Active autoimmune diseases such as Addison s disease, Hashimoto s thyroiditis, systemic lupus erythematosus, Sj(SqrRoot)(Delta)gren 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 CNS, heart, lungs, kidneys, skin, and GI tract will be allowed.
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Other immunodeficiency diseases
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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, and topical creams for small body areas is allowed.
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Evidence of rising PSA on ADT
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Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with patient s ability to carry out the treatment program.
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Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto)
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History of allergic reactions attributed to compounds of similar chemical or biologic composition to poxviral vaccines (e.g., vaccinia vaccine)
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Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin).
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History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis
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Previous serious adverse reactions to smallpox vaccination
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Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the Day 1 vaccination: (a) children less than or equal to 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.
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Receipt of an investigational agent within 28 days (or 60 days for an antibody-based therapy) before the first planned dose of study drugs.
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Patients who test positive for HBV or HCV
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Uncontrolled hypertension (SBP>170/ DBP>105)
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Patients who have had prior chemotherapy for prostate cancer.
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The subject has had evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder).
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The subject has active brain metastases or epidural disease.
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Patients with greater than or equal to grade 2 peripheral neuropathy at baseline.
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Patients with history of splenectomy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | United States | 20892 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Ravi A Madan, M.D., National Cancer Institute (NCI)
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 160048
- 16-C-0048