Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Arsenic Trioxide in Treating Patients With Stage IV Prostate Cancer That Has Not Responded to Previous Hormone Therapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	Any age	NCI	AECM-1199908270 NCI-T99-0077, AECM-CCRC-9929, NCT00004149, T99-0077

Objectives

1. Determine the efficacy of arsenic trioxide in patients with metastatic stage IVA or IVB hormone-refractory prostate cancer.
2. Determine the toxicity of this drug in this patient population.
3. Assess, in a preliminary manner, the effect of this drug on pain control in these patients.
4. Assess the potential value of serial quantitative prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) mRNA determinations in RNA from peripheral blood mononuclear cells as surrogate markers of disease response in patients treated with this drug.
5. Assess the pharmacokinetics and pharmacodynamics of this drug in these patients.
6. Assess the feasibility of using pretreatment bone marrow evaluation of PSA and PMSA mRNA levels and pi class glutathione S-transferase expression (i.e., eliminate glutathione levels) as potential correlates of disease response in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Diagnosis of stage IVA or IVB hormone-refractory prostate cancer
  • Evidence of metastatic disease by physical exam, bone scan, abdominal or pelvic CT scan, or chest X-ray
  • Must have failed at least 2 prior hormonal therapy regimens (e.g., luteinizing hormone-releasing hormone [LHRH] agonist plus antiandrogen and antiandrogen withdrawal)
  • Must have 2 successive increases in serum prostate-specific antigen (PSA) levels to at least 10 ng/mL measured at least 2 weeks apart
  • Must have castrate testosterone levels (no greater than 50 ng/dL) due to prior orchiectomy or continuing LHRH agonist therapy



• Obstructive uropathy and/or hydronephrosis allowed if adequate renal function and urinary drainage

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas and 8 weeks for suramin) and recovered

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since prior antiandrogen therapy (6 weeks for bicalutamide) (if PSA is increased from baseline)
• At least 2 weeks since prior corticosteroid therapy and recovered

Radiotherapy:

• At least 2 weeks since prior radiotherapy (4 weeks for strontium chloride Sr 90) and recovered

Surgery:

• See Disease Characteristics
• Recovered from prior surgery

Other:

• Recovered from acute toxicity of prior therapy
• At least 3 weeks since prior bisphosphonates
• No concurrent amphotericin B or other agent that prevents restoration of potassium or magnesium to normal levels and/or correction of QT interval to under 500 milliseconds

Patient Characteristics:

Age:

• Any age

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 2,500/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 9.0 g/dL

Hepatic:

• Bilirubin less than 2 mg/dL
• Transaminases less than 2.5 times upper limit of normal

Renal:

• See Disease Characteristics
• Creatinine less than 2 mg/dL
• Potassium between 4.0 and 5.5 mEq/L

  OR

• Magnesium between 1.5 and 2.5 mEq/L

Cardiovascular:

• No second-degree heart block without permanent pacemaker
• QT interval under 500 milliseconds

Other:

• No significant active infectious disease
• No grade 2 or greater peripheral neuropathy
• No other debilitating acute or chronic co-morbid medical, neurological, or psychiatric condition that would preclude study compliance

Expected Enrollment

A total of 17-37 patients will be accrued for this study within 12-24 months.

Outline

Patients receive arsenic trioxide IV over 2 hours on days 1-5 and 8-12 for one course. Treatment continues as biweekly infusions for at least 14 additional weeks in the absence of disease progression, unacceptable toxicity, or excessive increase in serum prostate-specific antigen.

Pain is assessed at baseline and then before each biweekly treatment.

Trial Contact Information

Trial Lead Organizations

Albert Einstein Cancer Center at Albert Einstein College of Medicine

Robert Gallagher, MD, Protocol chair		Ph: 718-430-2302 Email: rgallagher@acrom.yu.edu

Registry Information
Official Title		A Phase II Trial of Arsenic Trioxide in Advanced Hormone-Refractory Prostate Cancer
Trial Start Date		1999-09-27
Registered in ClinicalTrials.gov		NCT00004149
Date Submitted to PDQ		1999-10-08
Information Last Verified		2004-07-26
NCI Grant/Contract Number		CA13330

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