Phase II Metronomic Dosing, Etoposide, Cyclophosphamide, D0 Prostate Cancer

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier:
NCT00176605
First received: September 13, 2005
Last updated: April 18, 2014
Last verified: April 2014
  Purpose

Based on data supporting the use of cyclophosphamide and etoposide both as single agents in combination and a Phase I study showing acceptable toxicity with a chronic dosing regimen, we propose a Phase II clinical trial. This protocol establishes a model that will test the hypothesis that the use of etoposide and cyclophosphamide early in the course of prostate cancer progression, when fewer tumor cells are present, will have greater anti-tumor activity. We plan to treat patients with stage D0 prostate cancer to assess toxicity and anti-tumor activity.


Condition Intervention Phase
Prostate Cancer
Drug: Etoposide
Drug: Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Metronomic Dosing of Etoposide and Cyclophosphamide in Patients With Stage D0 Prostate Cancer.

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • PSA Response Rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The PSA response rate is the percentage of patients who have a PSA response. A PSA response will be considered a PSA decline of at least 50% must be confirmed by a second PSA value four or more weeks later. The reference PSA for these declines should be a PSA measured within 2 weeks prior to the initiation of therapy. Patients may not demonstrate clinical or radiographic evidence of disease progression during this period.


Secondary Outcome Measures:
  • Toxicities Related to Chronic Administration of Etoposide and Cyclophosphamide in Patients With Stage D0 Prostate Cancer. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    All patients who receive one dose of protocol therapy will be evaluable for toxicity. A total of 15 patients received at least one dose of protocol therapy. Adverse events are described in Adverse Event section.


Enrollment: 15
Study Start Date: May 2005
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 (Etoposide + Cyclophosphamide)
Therapy will be divided into 4 cycles. Each cycle will be composed of 6 weeks of therapy. Total duration of therapy is 24 weeks. Administration of etoposide (50 mg po qd) and cyclophosphamide (50 mg po qd) will alternate in 21 day intervals. Starting with etoposide, patients will receive 21 days of therapy, upon completion of etoposide therapy patients will then receive 21 days of cyclophosphamide therapy. Therapy will continue in this alternating manner for 24 weeks. Week 1 of each cycle, begins with etoposide; Week 4 of each cycle, begins with cyclophosphamide.
Drug: Etoposide
50 mg per day of Etoposide orally for 21 consecutive days. Etoposide will be alternated with oral cyclophosphamide. The drug is administered at night just prior to bed. Week 1 of each cycle will begin with etoposide.
Drug: Cyclophosphamide
50 mg per day of cyclophosphamide orally for 21 consecutive days. Cyclophosphamide will be alternated with oral etoposide. The drug is taken 2 hours after breakfast. The patient will be asked to increase hydration throughout the day. Recommendation is at least 6, 8oz glasses of water or other non-caffeinated beverage. Week 4 of the each cycle will begin with cylcophosphamide. Chronic administration of cyclophosphamide at this dose has been well tolerated

  Eligibility

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

Inclusion Criteria

  • Patients with histologically proven prostate cancer and tumors limited to the prostate (including seminal vesicle involvement, provided all visible disease was surgically removed) that have completed local therapy and have an rising PSA value, as defined in Section 5.1.5.
  • Prior androgen ablation therapy is allowed as long as the patient completed therapy at least 1 year prior to entry into this study. The patient must be fully recovered from such therapy and must not have demonstrated progression while on androgen ablation therapy.
  • Primary treatment to the prostate (surgery and/or radiation) must have been completed at least 3 months prior to entry into this study and the patient must be fully recovered from such therapy.
  • Patients must have a negative CT of the chest, abdomen and pelvis and bone scan. The scans must be completed within 4 weeks prior to the date of starting therapy.
  • PSA value for patients enrolled must be > 2 ng/ml with a doubling time of £ 12 months. PSA value > 2 ng/ml must be documented by two measurements at least four weeks apart. The final PSA measurement before study entry must be obtained within one week prior to therapy. This will be considered the baseline PSA. (Note: The website http://www.mskcc.org/mskcc/html/10088.cfm may be used to access a prostate normogram calculator.)
  • The following lab values must be obtained within 4 weeks prior to therapy:
  • ANC ≥1500/mm³,
  • Hemoglobin ≥ 10 g/dl
  • Platelet count ≥ 100,000/mm³
  • Serum creatinine ≤ 1.5 mg/dL
  • Total bilirubin ≤ 1.5 mg/dL
  • Liver function tests (SGOT, SGPT) ≤ 1.5 times the upper limit of the institution's normal range.
  • Men ≥ 18 years of age.
  • An estimated life expectancy of at least 6 months.
  • ECOG performance status ≤ 2.
  • Able to give informed, written consent.
  • Men must consent to using effective contraception (barrier method- latex condom) while on treatment and for 4 weeks after discontinuation of treatment.

Exclusion Criteria

  • Patients with active infections or known infection with HIV (HIV testing will not be performed as part of this study).
  • Any coexisting medical condition including uncontrolled cardiac, hepatic, renal or psychiatric disease defined as ³ Grade 3 (CTCAE Version 3).
  • Concurrent use of other investigational agent.
  • Patients that have previously received more than 2 months of therapy with any of the agents used in this study.
  • PSA value < 2 ng/ml.
  • Prior chemotherapy in the past 5 years.
  • Use of androgen ablation therapy within 1 year, or history of progression on androgen ablation therapy.
  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: NCT00176605

Locations
United States, New Jersey
Central Jersey Oncology Center
East Brunswick, New Jersey, United States, 08816
Robert Wood Johnson University Hospital/CINJ at Hamilton
Hamilton, New Jersey, United States, 08690
Morristown Memorial Hospital
Morristown, New Jersey, United States, 07962
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
Saint Peter's University Hospital
New Brunswick, New Jersey, United States, 08903
UMDNJ/Robert Wood Johnson Medical School
Newark, New Jersey, United States, 07103
Overlook Hospital
Summit, New Jersey, United States, 070901
Sponsors and Collaborators
Rutgers, The State University of New Jersey
Bristol-Myers Squibb
Investigators
Principal Investigator: Mark Stein, MD Rutgers, The State University of New Jersey
  More Information

No publications provided

Responsible Party: Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier: NCT00176605     History of Changes
Obsolete Identifiers: NCT00227643
Other Study ID Numbers: 080408, P30CA072720, 0220044931, CDR0000443482
Study First Received: September 13, 2005
Results First Received: September 17, 2013
Last Updated: April 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Rutgers, The State University of New Jersey:
prostate cancer
recurrent prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Cyclophosphamide
Etoposide phosphate
Etoposide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014