Docetaxel and Prednisone With or Without Vaccine Therapy 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: October 7, 2013
Last verified: October 2013
  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
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Biological: rilimogene-galvacirepvec
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:
  • Median overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The method of Kaplan and Meier will be used to characterize overall survival, and the stratified log-rank test will be used to compare this endpoint between treatment arms.


Secondary Outcome Measures:
  • Time to radiographic progression [ Time Frame: From randomization to radiographic progression, assessed up to 5 years ] [ Designated as safety issue: No ]
    The method of Kaplan and Meier will be used to characterize TTP, and the log-rank test will be used to compare this endpoint across treatments.

  • Objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Exact binomial confidence intervals will be used to describe objective response rates in both arms. With the study design, there will be 90% power to distinguish the PSA response rate of 69% in Arm A vs. 45% in Arm B using Fisher's exact test at a one-sided type I error of 10%.

  • Prostate-specific antigen (PSA) response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Exact binomial confidence intervals will be used to describe PSA response rates. The PSA response rate in Arm B is expected to be 45%. With the study design, there will be 90% power to distinguish the PSA response rate of 69% in Arm A vs. 45% in Arm B using Fisher's exact test at a one-sided type I error of 10%.

  • Immune response [ Time Frame: At 12 weeks ] [ Designated as safety issue: No ]
    Exact binomial confidence intervals will be used to describe immune response rates in both arms. The proportion of patients with immune response will be compared between the two arms using Fisher's exact test. The study will also evaluate whether anti-tumor immune responses to PSA are expanded and other prostate associated antigens are generated or expanded following chemotherapy.


Estimated Enrollment: 144
Study Start Date: August 2010
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (vaccine therapy and chemotherapy)
Patients receive vaccinia-PSA(L155)-TRICOM vaccine SC on day 1 of course 1 and fowlpox-PSA(L155)-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 twice daily 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.
Biological: rilimogene-galvacirepvec
Given SC
Biological: fowlpox-PSA-TRICOM vaccine
Given SC
Drug: docetaxel
Given IV
Drug: prednisone
Given PO
Active Comparator: Arm II (docetaxel, prednisone)
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 courses in the absence of disease progression or unacceptable toxicity.
Drug: docetaxel
Given IV
Drug: prednisone
Given PO

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 (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 I (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 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 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 II (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 courses 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 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 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 the past 4 weeks
  • Progressive disease while receiving ADT, defined by any 1 of the following:

    • At least 2 consecutive rises in serum 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

      • The greatest diameter of a target lymph node must be ≥ 2 cm with conventional techniques or ≥ 1 cm by spiral CT scan
    • 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 MRI)
  • Presence of visceral metastases
  • No known brain metastases
  • Life expectancy ≥ 18 months by Halabi nomogram
  • ECOG performance status 0-2
  • WBC ≥ 2,000/mm^3
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 2.0 mg/dL
  • AST and ALT ≤ 1.5 times upper limit of normal
  • Total bilirubin normal
  • Fertile patients must agree to use effective contraception before, during, and for ≥ 4 months after completion of study therapy
  • No 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
  • No 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
  • No 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
  • No allergy to eggs
  • No known intolerance or allergic reactions to docetaxel or compounds of similar chemical or biologic composition
  • No known history of allergic or intolerable reaction to vaccinia virus vaccination (e.g., smallpox)
  • Patients or close household contacts of patients cannot have close contact with persons with the following conditions 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 infection, or treated for other diseases with immunosuppressive agents)
    • Any other moderate or severe acute illness until the illness resolves
  • None of the following conditions within the past 6 months:

    • Stroke
    • Myocardial infarction
    • Unstable angina
    • NYHA class II-IV congestive heart failure
    • Significant cardiomyopathy requiring treatment
  • At least 4 weeks since prior nonsteroidal antiandrogen (e.g., flutamide) (6 weeks for bicalutamide or nilutamide)
  • More than 4 weeks since prior and no concurrent therapy with any of the following:

    • Other systemic corticosteroids

      • Inhaled, intranasal, or topical corticosteroids allowed
      • No steroid eyedrops at least 2 weeks before and 4 weeks after protocol 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
  • More than 4 weeks since prior external-beam radiation therapy
  • At least 4 weeks since any prior treatment and recovered
  • More than 4 weeks since surgery
  • More than 6 months since prior chemotherapy

    • Prior and/or concurrent bisphosphonates allowed
  • More than 2 weeks since prior and no concurrent CYP3A4 substrates, inhibitors, or inducers
  • No prior chemotherapy for metastatic prostate cancer
  • No prior radiotherapy to > 30% of bone marrow
  • No prior anticancer vaccine
  • No prior splenectomy
  • No other concurrent investigational agents or anticancer therapy other than androgen-deprivation treatment
  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
Principal Investigator: Douglas McNeel Eastern Cooperative Oncology Group
  More 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, CDR0000675173, E1809, E1809, U10CA021115
Study First Received: June 15, 2010
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Prednisone
Docetaxel
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 20, 2014