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

Rutgers The State University of New Jersey

Status and phase: Completed; Phase 2

Conditions: Prostate Cancer

Treatments: Drug: Cyclophosphamide; Drug: Etoposide

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00176605

080408

0220044931 (Other Identifier)

P30CA072720 (U.S. NIH Grant/Contract)

CDR0000443482

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

15 participants in 1 patient group

Arm 1 (Etoposide + Cyclophosphamide)

Experimental group

Description:

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.

Treatment:

Drug: Etoposide

Drug: Cyclophosphamide