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

NCT00970203 | Completed Phase 2 Results DMC

• 1 other identifier: 06-070
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.).

Conditions

Cancer of Prostate; Cancer of the Prostate; Neoplasms, Prostate; Neoplasms, Prostatic; Prostate Cancer; Prostate Neoplasms; Prostatic Cancer

Keywords

Vaccine; Androgen Ablation; PSA Progression

Outcome Measures

Primary Outcomes (3)

• Percentage of Patients to Successfully Generate and Administer the Alpha-DC1 Vaccine

  The percentage of patients for which the alpha-DC1 vaccine was generated and for which 4 vaccine injections were administered (1 injection every 4 weeks).

  16 weeks

• Tolerability and Toxicity of the Alpha-DC1 Vaccine

  The percentage of patients who experienced vaccine related toxicity.

  16 weeks

• The Effect of the DC1 Vaccine on Time to PSA Progression Compared to AA Alone

  The mean difference between time to relapse on androgen ablation plus alpha DC-1 vaccine vs androgen ablation

  Approximately 18 months

Secondary Outcomes (5)

• Change in PSA Velocity Prior to and Following the Proposed Treatment.

  Approximately 18 months

• 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)

  Approximately 17 weeks

• Evaluate the Vaccination-induced Changes of Th1/Th2 Profiles of the Responses to PAP and PSMA

  Approximately 18 to 24 months

• 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

  Approximately 18 to 24 months

• 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

  Approximately 18 to 24 months

Study Arms (2)

Cohort A

EXPERIMENTAL

3 months of androgen ablation followed at PSA progression by 3 months of the combination of androgen ablation + DC1 vaccine AA: Lupron 22.5 mg or Zoladex 10.8 mg DC vaccine: intradermal (id) vaccine of 3-5 x 10e6 cells

Biological: androgen ablation (AA); Biological: DC1 vaccine

Cohort B

EXPERIMENTAL

3 months of the combination of androgen ablation + DC1 vaccine followed at PSA progression by 3 months of androgen ablation AA: Lupron 22.5 mg or Zoladex 10.8 mg DC vaccine: intradermal (id) vaccine of 3-5 x 10e6 cells

Biological: androgen ablation (AA); Biological: DC1 vaccine

Interventions

androgen ablation (AA) BIOLOGICAL

Lupron 22.5 mg or Zoladex 10.8 mg

Cohort A; Cohort B

DC1 vaccine BIOLOGICAL

3-5 x 10e6 cells total

Also known as: alpha dendritic cell 1 vaccine

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• University of Pittsburgh: collaborator

Study Sites (1)

University of Pittsburgh Cancer institute

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

Despite numerous attempts to obtain required data from the previous IND holder where the data is housed, including attempts to contact study PI and team, no responses were obtained and no data were available for this some Outcome Measures.

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

adrienne.groman@roswellpark.org

7168451300

Study Officials

• Leonard J Appleman, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2009
• First Posted: September 2, 2009
• Study Start: September 1, 2009
• Primary Completion: October 5, 2018
• Study Completion: October 5, 2019
• Last Updated: November 3, 2020
• Results First Posted: May 7, 2020

Record last verified: 2020-10

Locations

US (1)