A Neoadjuvant Study of Androgen Ablation Combined With Cyclophosphamide and GVAX Vaccine for Localized Prostate Cancer

NCT01696877 | Completed Phase 1 Results DMC

• 2 other identifiers: J1265NA_00073453
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to see if an investigational prostate cancer vaccine, called GVAX, can safely be given together with a single intravenous injection of a drug called cyclophosphamide to men that will undergo surgery to remove their cancerous prostate glands who have also received standard hormonal therapy.

Conditions

Prostate Cancer Adenocarcinoma in Situ

Outcome Measures

Primary Outcomes (1)

• Intraprostatic CD8+ T Cell Infiltration

  CD8+ T cell infiltration (quantified as log\[CD8 density\]) into the prostate from harvested prostate glands in men with localized prostate cancer receiving neoadjuvant Androgen deprivation therapy alone (2 weeks prior to surgery), or cyclophosphamide and GVAX followed by Androgen deprivation therapy, (with cyclophosphamide/GVAX administered 4 weeks prior to prostatectomy, and Androgen deprivation therapy administered 2 weeks prior to prostatectomy).

  2 years

Secondary Outcomes (7)

• Intraprostatic CD4+ T Cell and Treg Infiltration

  2 years

• Quantification of Tissue Androgen Concentrations

  2 years

• Quantification of Markers of Apoptosis

  2 years

• Pathological Complete Responses

  2 years

• Serum Antibodies to Prostate-associated Antigens

  2 years

Study Arms (2)

Degarelix

ACTIVE COMPARATOR

Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3.

Drug: degarelix acetate

Cyclophosphamide, GVAX and Degarelix

EXPERIMENTAL

Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg.

Drug: degarelix acetate; Drug: Cyclophosphamide; Drug: GVAX

Interventions

degarelix acetate DRUG

Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow.

Also known as: Firmagon

Cyclophosphamide, GVAX and Degarelix; Degarelix

Cyclophosphamide DRUG

Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders.

Also known as: Cytoxan, Neosar

Cyclophosphamide, GVAX and Degarelix

GVAX DRUG

GVAX is granulocytemacrophage -colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer

Also known as: granulocytemacrophage -colony stimulating factor -secreting cell-based (PC3/LNCaP)immunotherapy

Cyclophosphamide, GVAX and Degarelix

Eligibility Criteria

• Age: 21 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs
• Initial prostate biopsy is available for central pathologic review, and is confirmed to show at least 2 positive cores and a maximum Gleason sum of ≥ 7
• Radical prostatectomy has been scheduled at Johns Hopkins Hospital
• Age ≥ 21 years
• Eastern Cooperative Oncology Group performance status 0-1, or Karnofsky score ≥ 70%
• Adequate bone marrow, hepatic, and renal function:
• White Blood Count \> 3,000 cells/mm3
• Absolute neutrophil count \> 1,500 cells/mm3
• Hemoglobin \> 9.0 g/dL
• Platelet count \> 100,000 cells/mm3
• Serum creatinine \< 2.0 mg/dL
• Serum bilirubin \< 2 mg/dL
• Alanine aminotransferase \< 2 × upper limit of normal (ULN)
• Aspartate aminotransferase \< 2 × ULN
• Alkaline phosphatase \< 2 × ULN

You may not qualify if:

• Presence of known lymph node involvement or distant metastases
• Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors
• Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate cancer
• Prior immunotherapy/vaccine therapy for prostate cancer
• Previous or concurrent use of cyclophosphamide
• Concomitant treatment with other hormonal therapy or 5a-reductase inhibitors
• Current use of systemic corticosteroids or use of corticosteroids within 4 weeks of enrollment (inhaled corticosteroids for asthma or Chronic obstructive pulmonary disease are permitted)
• Use of experimental agents for prostate cancer within the past 3 months
• Known allergy to cyclophosphamide or G-colony stimulating factor /granulocytemacrophage-colony stimulating factor
• Known hypersensitivity to materials of bovine origin (e.g. fetal bovine serum), or other components of GVAX which include Dimethyl sulfoxide and hydroxyethyl starch as well as small amounts of porcine trypsin and DNase
• History or presence of autoimmune disease requiring systemic immunosuppression (including but not limited to: inflammatory bowel disease, systemic lupus erythematosus, vasculitis, rheumatoid arthritis, scleroderma, multiple sclerosis, hemolytic anemia, Sjögren syndrome, and sarcoidosis)
• Other concurrent malignancies, with the exception of non-melanoma skin cancers and superficial bladder cancer
• Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or psychiatric illnesses that would make the patient a poor study candidate
• Known prior or current history of HIV and/or hepatitis B/C

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• David H. Koch Charitable Foundation: collaborator
• BioSante Pharmaceuticals: collaborator

Study Sites (1)

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Interventions

acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Emmanuel S. Antonarakis, M.D., principal investigator
• Organization: Johns Hopkins University

eantona1@jhmi.edu

443-287-0553

Study Officials

• Emmanual Antonarakis, M.D

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2012
• First Posted: October 1, 2012
• Study Start: January 18, 2013
• Primary Completion: August 1, 2017
• Study Completion: December 18, 2018
• Last Updated: March 28, 2019
• Results First Posted: November 1, 2018

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)