Docetaxel and Prednisone With or Without Vaccine in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01145508
First received: June 15, 2010
Last updated: July 22, 2014
Last verified: January 2014
  Purpose

This randomized phase II trial is studying giving docetaxel and prednisone together with or without vaccine therapy to see how well it works in treating patients with metastatic hormone-resistant prostate cancer. 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 or by stopping them from dividing. Vaccines made from an antigen may help the body build an effective immune response to kill tumor cells. It is not yet known giving docetaxel and prednisone together is more effective with or without vaccine therapy in treating prostate cancer.


Condition Intervention Phase
Adenocarcinoma of the Prostate
Castrate-resistant Metastatic Prostate Cancer
Biological: PSA-TRICOM vaccine
Biological: fowlpox-PSA-TRICOM vaccine
Drug: Docetaxel
Drug: Prednisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Docetaxel With or Without PSA-TRICOM Vaccine in Patients With Castrate-Resistant Metastatic Prostate Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Assessed every 3 months for 2 years, and then every 6 months for 3 years ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization to death or the date of last known alive.


Enrollment: 10
Study Start Date: August 2010
Estimated Study Completion Date: January 2017
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (vaccine and chemotherapy)
Patients receive vaccinia-PSA(L155)-TRICOM vaccine subcutaneously (SC) on day 1 and fowlpox-PSA(L155)-TRICOM vaccine SC on days 15, 29, 43, and 57. Beginning on day 85, patients receive chemotherapy in a 21-day cycle. Docetaxel is administered intravenously (IV) over 1 hour on day 1. Prednisone is given orally (PO) twice daily on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Biological: PSA-TRICOM vaccine
Given SC
Other Names:
  • Recombinant Vaccinia-PSA(L155)-TRICOM (NSC 717170)
  • Recombinant Vaccinia-PSA(L155)-TRICOM
  • rV-PSA(L155)-TRICOM
  • Vaccinia-PSA(3A)-TRICOM
  • rV-PSA(3A)-TRICOM
  • PROSTVAC-V/TRICOM
Biological: fowlpox-PSA-TRICOM vaccine
Given SC
Other Names:
  • Recombinant Fowlpox-PSA(L155)-TRICOM
  • rF-PSA(L155)-TRICOM
  • Fowlpox-PSA(3A)-TRICOM
  • rF-PSA(3A)-TRICOM
  • PROSTVAC-F/TRICOM
Drug: Docetaxel
Given IV
Other Names:
  • RP56976
  • Taxotere
Drug: Prednisone
Given PO
Other Names:
  • Deltasone
  • Orasone
  • Medicorten
  • Panasol-S
  • Liquid-Pred
Active Comparator: Arm B (chemotherapy)
Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO twice daily on days 1-21. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Docetaxel
Given IV
Other Names:
  • RP56976
  • Taxotere
Drug: Prednisone
Given PO
Other Names:
  • Deltasone
  • Orasone
  • Medicorten
  • Panasol-S
  • Liquid-Pred

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the overall survival in patients treated with PSA-TRICOM 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 RECIST) between the two treatment groups in those patients with measurable disease.

III. To evaluate 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: This is a multicenter study. Patients are stratified according to disease progression (prostate-specific antigen (PSA) vs radiographic criteria), extraskeletal metastases (yes vs no), and prior bisphosphonate (yes vs no). Patients are randomized to 1 of 2 treatment arms.

ARM A (vaccine and chemotherapy): Patients receive vaccinia-PSA(L155)-TRICOM vaccine subcutaneously (SC) on day 1 of course 1 and fowlpox-PSA(L155)-TRICOM vaccine SC on days 15, 29, 43, and 57. Beginning on day 85, patients receive chemotherapy in a 21-day cycle. Docetaxel is administered intravenously (IV) over 1 hour on day 1. Prednisone is given orally (PO) twice daily on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 cycles 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 twice daily on days 1-21. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection to measure frequency of PSA-specific T-cells and other biomarkers of immune response.

After completion of study therapy, patients are followed up every 3-6 months for 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate

    • Evidence of metastatic disease by the presence of soft tissue and/or bone metastases on computed tomography (CT) scan of the abdomen and/or pelvis, or bone scintigraphy
  • Castrate-resistant disease defined by the following:

    • Must have received standard-of-care androgen-deprivation treatment (ADT) (e.g., surgical castration, gonadotropin-releasing hormone [GnRH], or antagonist treatment). Patients on concurrent gonadotropin-releasing hormone (GnRH) analogue or antagonist must continue on this treatment throughout this study
    • Must have been treated with nonsteroidal antiandrogen with evidence of subsequent disease progression
    • Must have castration levels of testosterone (< 50 ng/dL) within 4 weeks of randomization
  • Progressive disease while receiving ADT, defined by any 1 of the following:

    • At least 2 consecutive rises in serum prostate-specific antigen (PSA) (each value ≥ 2.0 ng/mL) obtained at a minimum of 1-week intervals
    • Measurable disease with ≥ 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 ≥ 1 cm by CT scan (1.5 cm in shortest axis for lymph nodes)
    • Non-measurable (bone) disease consisting of ≥ 2 new areas of uptake by bone scan consistent with metastatic disease compared to previous imaging during castration therapy; ambiguous results must be confirmed by other imaging modalities (e.g., X-ray, CT scan, or magnetic resonance image [MRI])
  • ECOG performance status 0-1
  • White blood cell (WBC) count ≥ 2,000/mm^3
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 2.0 mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 times upper limit of normal (ULN)
  • Total bilirubin < institutional ULN
  • At least 4 weeks since any prior treatment and recovered
  • Fertile patients must agree to use effective contraception before, during, and for ≥ 4 months after completion of study therapy

Exclusion criteria:

  • Presence of visceral metastases
  • Alkaline phosphatase (IU/L) > 2X institutional upper limit of normal
  • Lactate dehydrogenase (LDH) (U/L) > 2X institutional upper limit of normal
  • Other concurrent investigational agents or anticancer therapy other than androgen-deprivation treatment
  • Prior anticancer vaccine
  • Treatment with any of the following within 4 weeks of randomization or while on study:

    • systemic corticosteroids (excluding prednisone and dexamethasone administered as part of study protocol)

      • inhaled, intranasal, or topical corticosteroids allowed
      • steroid eye drops are contraindicated for 2 weeks prior to vaccination and for at least 4 weeks after vaccinia vaccination
    • PC-SPES
    • Saw palmetto
    • Megestrol
    • Ketoconazole
    • 5-α-reductase inhibitors

      • Patients on 5-α-reductase inhibitors for > 28 days may continue these agents throughout the study
      • May not start therapy with 5-α-reductase inhibitors during study therapy
    • Diethyl stilbestrol
    • Any other hormonal agent or supplement with possible anticancer activity
  • Prior external-beam radiation therapy with 4 weeks of randomization
  • Prior radiotherapy to > 30% of bone marrow
  • Prior surgery within 4 weeks of randomization
  • Prior chemotherapy within 6 months of randomization

    • Prior and/or concurrent bisphosphonates allowed
  • Prior chemotherapy for metastatic prostate cancer
  • Known infection with HIV 1 or HIV 2, HTLV-1, hepatitis B, or hepatitis C, or any other potentially immunosuppressive infection

    • Patients must have negative serologic testing for HIV, hepatitis B surface antigen, and hepatitis C
  • History of autoimmune disease requiring active immunosuppressive therapy or ≥ grade 2 organ dysfunction as a result of known autoimmune disease

    • Patients must have antinuclear antibody (ANA) titer < 1:320
  • Prior splenectomy
  • Other active malignancy except nonmelanoma skin cancer, carcinoma in situ of the bladder, or other adequately treated cancer that has been free of recurrence for ≥ 3 years
  • Allergy to eggs
  • Intolerance or allergic reactions to docetaxel or compounds of similar chemical or biologic composition
  • History of allergic or intolerable reaction to vaccinia virus vaccination (e.g., smallpox)
  • Close contact with persons with the following conditions for patients or close household contacts of patients within 3 weeks after potential vaccinia immunization:

    • History of eczema, active eczema or other acute, chronic, or exfoliative skin conditions, including Darier's disease (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or open wounds)
    • Pregnant or nursing women
    • Children under 3 years of age
    • Immunodeficient or immunosuppressed persons (e.g., HIV, or treated for other diseases with immunosuppressive agents)
    • Any other moderate or severe acute illness until the illness resolves
  • Brain metastases
  • History of recent (within 6 months) stroke, myocardial infarction, unstable angina, New York Heart Association class II-IV congestive heart failure or significant cardiomyopathy requiring treatment
  • Treatment with strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) within 2 weeks of beginning docetaxel through its discontinuation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01145508

Locations
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Hematology and Oncology Associates
Chicago, Illinois, United States, 60611
Hematology Oncology Associates of Illinois-Highland Park
Highland Park, Illinois, United States, 60035
Presence Saint Mary's Hospital
Kankakee, Illinois, United States, 60901
North Shore Hematology Oncology
Libertyville, Illinois, United States, 60048
Illinois Cancer Specialists-Niles
Niles, Illinois, United States, 60714
Hematology Oncology Associates of Illinois - Skokie
Skokie, Illinois, United States, 60076
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
New York University Langone Medical Center
New York, New York, United States, 10016
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Study Chair: Douglas G McNeel, MD University of Wisconsin, Madison
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01145508     History of Changes
Other Study ID Numbers: NCI-2011-02048, NCI-2011-02048, E1809, U10CA021115
Study First Received: June 15, 2010
Results First Received: April 25, 2014
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
docetaxel
PSA-TRICOM vaccine
castrate-resistant metastatic prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Docetaxel
Prednisone
Metronidazole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on October 19, 2014