Dendritic Cell (DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
Pawel Kalinski, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00970203
First received: September 1, 2009
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

This study will evaluate the feasibility, safety, and efficacy of intradermal vaccination of prostate cancer patients with alpha-type-1-polarized dendritic cells (DC1) loaded with apoptotic allogeneic tumor (LNCap). The study will target men with recurrent prostate cancer, who failed local therapy, have no measurable metastasis, but have a rising PSA with a doubling time of less than 10 months. The selection of this study group enables us to evaluate time to PSA progression, a highly relevant, clinical primary endpoint of efficacy in this two arm study. In order to facilitate infiltration of vaccination-induced T cells into tumor site(s) and to reduce tumor-specific tolerance, subjects will receive the vaccine in combination with limited androgen ablation (AA) with a LHRH analogue for 3 months. Subjects will be randomly assigned to one of two cohorts. In cohort A subjects will be first treated with limited AA alone for 3 months, and at the time of PSA relapse (PSA ≥ 1 ng/dL) will receive the DC vaccine in conjunction with AA. In cohort B, the sequence of treatment will be reversed. Efficacy will be estimated as the within-subject difference in time to PSA relapse following the combination treatment as compared to the AA alone, thus, each subject will serve as his own control. All subjects will commence the DC1-based vaccination 2 weeks prior to treatment with the LHRH analogue. Each subject will receive 1 intradermal (i.d.) dose of the vaccine at weeks 1, 5, 9, and 13 for a total of 4 doses. Additional courses of vaccination may be administered to subjects without evidence of disease progression every 3 months (±1 month) for up to 12 months depending on the number of doses originally produced and available after the 4 intended protocol doses. All doses of the vaccine will be administered intradermally (i.d.).


Condition Intervention Phase
Prostate Cancer
Biological: androgen ablation + dendritic cell vaccine
Biological: androgen ablation plus dendritic cell vaccine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Feasibility, Safety and Efficacy Evaluation of Alpha-Type 1 Dendritic Cell(DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With PSA Progression After Local Therapy for Prostate Cancer

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Ability to successfully generate and administer the alpha-DC1 vaccine [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    4 vaccine injections, 1 injection every 4 weeks

  • Assess the tolerability and toxicity of the alpha-DC1 vaccine [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    4 vaccine injections, 1 injection every 4 weeks

  • The effect of the DC1 vaccine on time to PSA progression compared to AA alone [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in PSA velocity prior to and following the proposed treatment. [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Evaluate (in all subjects) the vaccination-induced DTH responses to LNCap, the cell line vaccine, and to compare this with vaccination-induced responses to tumor-untreated antigen (KLH) [ Time Frame: Approximately 17 weeks ] [ Designated as safety issue: No ]
  • Evaluate the vaccination-induced changes of Th1/Th2 profiles of the responses to PAP and PSMA [ Time Frame: Approximately 18 to 24 months ] [ Designated as safety issue: No ]
  • Evaluate the CTL responses in blood to the whole LNCap cells (in all subjects) and (in all subjects who are HLA-A2 positive) the CTL responses to HLA-A2.1 restricted peptides derived from PAP and PSMA [ Time Frame: Approximately 18 to 24 months ] [ Designated as safety issue: No ]
  • Comprehensively evaluate the CD4+ and CD8+ T cell responses (fine specificity and Th1/Th2/Treg cytokine profile) to the previously-identified and novel immunogenic epitopes of PAP and PSMA, using the EPIMAX system [ Time Frame: Approximately 18 to 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: September 2009
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ablation followed by Ablation + vaccine
3 months of androgen ablation (AA) to be followed at PSA progression by 3 months of the combination of AA and alpha-type 1 dendritic cell vaccine (DC1)
Biological: androgen ablation + dendritic cell vaccine
androgen ablation (AA) to be followed at PSA progression by 3 months of the combination of AA alpha-type 1 dendritic cell vaccine (DC1)
Experimental: Ablation with vaccine followed by Ablation
3 months of the combination of AA and alpha-type 1 dendritic cell vaccine followed at PSA progression by 3 months of AA.
Biological: androgen ablation plus dendritic cell vaccine
3 months of the combination of AA and alpha-type 1 dendritic cell vaccine followed at PSA progression by 3 months of AA.

  Show Detailed Description

  Eligibility

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

Eligibility Criteria

  • Patients with histologically proven prostate cancer and tumors limited to the prostate (including seminal vesicle involvement, provided all visible disease was surgically removed) who have completed local therapy and have an elevated PSA after surgery or rising PSA after radiation therapy, as defined below.
  • Age 18 years or older
  • Histologically confirmed diagnosis of prostate cancer.
  • Previous treatment with definitive surgery or radiation therapy or both.
  • No evidence of metastatic disease on physical exam, CT/MRI/CXR (see Section 7.1 for radiologic imaging), and bone scan within 4 weeks prior to randomization.
  • Prior neoadjuvant/adjuvant hormonal, androgen deprivation therapy, or chemotherapy is allowed if it was last used > 12 months prior to first vaccination.
  • No therapy modulating testosterone levels (such as leuteinizing-hormone releasing-hormone agonists/antagonists and antiandrogens) is permitted within 12 months prior to first vaccination. Agents such as 5α-reductase inhibitors, ketoconazole, megestrol acetate, systemic steroids (replacement doses of steroids are allowed), PC-SPES, and Saw Palmetto are not permitted at any time during the period that the PSA values are being collected.
  • Hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150 ng/dL or > 6 nmol/L at the time of enrollment within 4 weeks prior to randomization.
  • All patients must have evidence of biochemical progression as determined by a reference PSA value followed by 1 confirmatory rising PSA value, higher than the previous value, obtained at least 2 weeks apart. All of these PSA values must be obtained at the same reference lab, and all must be done within 6 months prior to enrollment.
  • The most recent of the PSA values must be ≥ 2.0 ng/mL. This measurement must be obtained within 1 month prior to enrollment.
  • The PSA doubling time (PSA-DT) must be less than 12 months.
  • ECOG performance status 0 or 1.
  • Patients must have normal organ and marrow function as defined below:

    • Absolute neutrophil count > 1,500/µL
    • Platelets > 100,000/µL
    • Total bilirubin 1.5 x upper limit of normal (ULN)
    • SGOT (AST) and SGPT (ALT) < 2.5 x institutional ULN
    • Creatinine 1.5 x ULN
  • The effects of dendritic cell vaccines on the developing human fetus are unknown. For this reason men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.

Exclusion Criteria

  • Patients must not be receiving other investigational agents or concurrent anticancer therapy.
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients must not have active eczema, atopic dermatitis, or other exfoliative skin conditions (e.g., burns, impetigo, varicella zoster, severe acne, contact dermatitis, psoriasis, herpes or other open rashes or wounds).
  • Presence of an active acute or chronic infection, including urinary tract infection, HIV or viral hepatitis. HIV patients are excluded based on immunosuppression which may render them unable to respond to the vaccine; patients with chronic hepatitis are excluded because of concern that hepatitis could be exacerbated by the injections. If clinically indicate, HIV/viral hepatitis testing will be performed to confirm status.
  • Patients with a history of auto-immune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Patients receiving replacement thyroid hormone would be eligible.
  • No concurrent use of systemic steroids, except for local (topical, nasal, or inhaled) steroid use. Adrenal replacement doses of corticosteroids are allowed.
  • Subjects with concurrent additional malignancy (with exception of non-melanoma skin cancers and superficial bladder cancer or malignancy within last 3 years).
  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: NCT00970203

Contacts
Contact: Appleman Leonard, MD, PhD 412-648-6507 applemanlj@upmc.edu
Contact: Diana Long, R.N. (412) 647-8475 longdl@upmc.edu

Locations
United States, Pennsylvania
University of Pittsburgh Cancer institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Leonard J Appleman, MD, PhD    412-648-6507    applemanlj@upmc.edu   
Sub-Investigator: David Friedland, MD         
Sub-Investigator: Jodie Maranchie, MD         
Sponsors and Collaborators
Pawel Kalinski
Investigators
Principal Investigator: Appleman J Leonard, MD, PhD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Pawel Kalinski, Professor of Surgery, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00970203     History of Changes
Other Study ID Numbers: 06-070
Study First Received: September 1, 2009
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
Prostate
Androgen Ablation
PSA Progression

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014