Randomized Phase II Trial of Docetaxel With or Without PSA-TRICOM Vaccine in Patients With Castrate-Resistant Metastatic Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- Docetaxel
- Conditions
- Hormone-Resistant Prostate Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 10
- Locations
- 14
- Primary Endpoint
- Overall Survival
- Status
- Terminated
- Last Updated
- 8 years ago
Overview
Brief Summary
This randomized phase II trial studies how well docetaxel and prednisone with or without vaccine therapy works in treating patients with hormone-resistant prostate cancer that has spread to other parts of the body. Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Vaccines made from an antigen may help the body build an effective immune response to kill tumor cells. It is not yet known whether docetaxel and prednisone are more effective with or without vaccine therapy in treating prostate cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the overall survival in patients treated with PSA-TRICOM (fowlpox-PSA-TRICOM vaccine and rilimogene-galvacirepvec) and docetaxel chemotherapy versus docetaxel chemotherapy only. SECONDARY OBJECTIVES: I. To evaluate the time to radiographic progression after beginning docetaxel chemotherapy in patients previously treated with PSA-TRICOM vaccine versus those not treated with this vaccine. II. To compare objective responses (according to Response Evaluation Criteria in Solid Tumors \[RECIST\]) between the two treatment groups in those patients with measurable disease. III. To evaluate prostate-specific antigen (PSA) response rates (decline \>= 50%) in patients treated with PSA-TRICOM and docetaxel chemotherapy versus docetaxel chemotherapy only. IV. To evaluate immune responses elicited in patients treated before and after docetaxel chemotherapy. V. To evaluate the association between development of prostate antigen-specific immune responses and time to progression and overall survival. VI. To evaluate the association of predicted survival (by Halabi nomogram) with actual survival in patients treated with PSA-TRICOM vaccine versus those not treated with this vaccine. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A (vaccine and chemotherapy): Patients receive rilimogene-galvacirepvec subcutaneously (SC) on day 1 of course 1 and fowlpox-PSA-TRICOM vaccine SC on days 15, 29, 43, and 57 of course 1. Beginning on day 85 (day 1 of course 2), patients receive docetaxel intravenously (IV) over 1 hour on day 1 and prednisone orally (PO) twice daily (BID) on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. ARM B (chemotherapy): Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient must have histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
- •Patient must have metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (computed tomography \[CT\] of abdomen/pelvis, bone scintigraphy)
- •Patient must have castrate-resistant disease, defined as follows:
- •Patient must have received standard of care androgen deprivation treatment (ADT) before trial entry (surgical castration versus gonadotropin-releasing hormone \[GnRH\] analogue or antagonist treatment); subjects receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study
- •Patient must have been treated previously with a nonsteroidal antiandrogen, with evidence of subsequent disease progression; subjects must be off use of anti-androgen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to randomization; subjects who demonstrate an anti-androgen withdrawal response, defined as a \>= 25% decline in PSA within 4-6 week of stopping a nonsteroidal antiandrogen are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal
- •Patient must have castration levels of testosterone (\< 50 ng/dL) within 4 weeks prior to randomization
- •Patient must have progressive disease while receiving ADT as defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria:
- •PSA: at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, and each value \>= 2.0 ng/mL
- •Measurable disease: \>= 50% increase in the sum of the cross products of all measurable lesions or the development of new measurable lesions by RECIST criteria version 1.1; the greatest diameter of a target lesion must be at least 1.0 cm by CT scan (1.5 cm in shortest axis for lymph nodes)
- •Non-measurable (bone) disease: the appearance of two or more new areas of uptake on bone scan consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or magnetic resonance imaging \[MRI\])
Exclusion Criteria
- Not provided
Arms & Interventions
Arm A (vaccine therapy and chemotherapy)
Patients receive rilimogene-galvacirepvec SC on day 1 of course 1 and fowlpox-PSA-TRICOM vaccine SC on days 15, 29, 43, and 57 of course 1. Beginning on day 85 (day 1 of course 2), patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Docetaxel
Arm A (vaccine therapy and chemotherapy)
Patients receive rilimogene-galvacirepvec SC on day 1 of course 1 and fowlpox-PSA-TRICOM vaccine SC on days 15, 29, 43, and 57 of course 1. Beginning on day 85 (day 1 of course 2), patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm A (vaccine therapy and chemotherapy)
Patients receive rilimogene-galvacirepvec SC on day 1 of course 1 and fowlpox-PSA-TRICOM vaccine SC on days 15, 29, 43, and 57 of course 1. Beginning on day 85 (day 1 of course 2), patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Prednisone
Arm A (vaccine therapy and chemotherapy)
Patients receive rilimogene-galvacirepvec SC on day 1 of course 1 and fowlpox-PSA-TRICOM vaccine SC on days 15, 29, 43, and 57 of course 1. Beginning on day 85 (day 1 of course 2), patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Recombinant Fowlpox-PSA(L155)/TRICOM Vaccine
Arm A (vaccine therapy and chemotherapy)
Patients receive rilimogene-galvacirepvec SC on day 1 of course 1 and fowlpox-PSA-TRICOM vaccine SC on days 15, 29, 43, and 57 of course 1. Beginning on day 85 (day 1 of course 2), patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Rilimogene Galvacirepvec
Arm B (docetaxel, prednisone)
Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Docetaxel
Arm B (docetaxel, prednisone)
Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm B (docetaxel, prednisone)
Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Prednisone
Outcomes
Primary Outcomes
Overall Survival
Time Frame: Assessed every 3 months for 2 years, and then every 6 months for 3 years
Overall survival is defined as the time from randomization to death or the date of last known alive.