A Phase II Study of Ara-C (Cytarabine) in Men With Androgen Independent Prostate Cancer (SLAP)

This is a single-arm, open label phase II trial of the investigational agent, Ara-C (cytarabine), in patients diagnosed with hormone refractory prostate cancer whose disease has progressed on or deemed not suitable for standard chemotherapy with docetaxel. Ara-C appears to inhibit DNA synthesis and is cytotoxic to a wide variety of mammalian cells. Recent discoveries have suggested the role of gene fusions in the ETS family of transcription factors as important for the development of prostate cancer. Ara-C appears to block ETS genes, suggesting that it is worthwhile to explore Ara-C as a potential new treatment for patients with hormone refractory prostate cancer given that there is no standard of care for the proposed patient population. In this study, Ara-C will be administered intravenously for 2 days every 3 weeks (1 cycle). Treatment will be for 6 cycles if tolerated and may be continued in patients who are responding and do not have severe toxicity.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Cytarabine

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Biopsy-proven prostate cancer or clinical picture consistent with metastatic prostate cancer with high level of serum PSA (> 20ng/ml)
• At least 4 weeks after docetaxel treatment and have at least 2 consecutive rising PSAs measured at least 2 weeks apart
• Progression on or intolerance of docetaxel chemotherapy
• ECOG performance status ≤ 2
• Adequate organ and marrow function

Exclusion Criteria:

• Prior treatment with cytarabine
• Receiving any other investigational or anticancer agents
• Uncontrolled intercurrent illness
• Active malignancy at any other site excluding squamous cell or basal cell carcinomas of the skin
• Radiotherapy within the past 4 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cytarabine; eligible patients will receive cytarabine, starting at 075g/m2 and escalating to a maximum of 1.25g/m2, BID IV for 2 days every three weeks for 6 or more cycles if tolerated.	Drug: Cytarabine; Initially given at 1g/m2 bid for 2 days every 3 weeks over 2 hours. The dose will be escalated: level 1 - 1.25g/m2, level 2, 1.5g/m2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA response	PSA levels will be collected at screening, baseline, 2 weeks following study termination, and upon followup to determine PSA level response to treatment.	50% decline in PSA from baseline, confirmed by a second measurement ≥3 weeks later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain response	Patients will complete Present Pain Intensity (PPI) scale a baseline, every three weeks during treatment and at the end of study.	Baseline median PPI with no concomitant increase in analgesic score/pain
QOL response	Quality of Life (QOL) will be assessed with the Functional Assessment of Cancer Therapy - Prostate questionnaire, self administered by patients.	Baseline to two measurements obtained at least three weeks apart
PSA progression free survival	Time between randomization date and the date of PSA progression (>25% increase from baseline) or the date of death due to prostate cancer, whichever occurs first.	Baseline and the date of PSA progression or the date of death due to prostate cancer, whichever occurs first.
Measurable disease response	Radiological measurement of effect. Measurement at baseline, and every 3 cycles	Every 3 cycles (9 weeks)

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Anthony Joshua, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: May 28, 2007
• First Submitted That Met QC Criteria: May 29, 2007
• First Posted (Estimate): May 30, 2007

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Prostate; Phase II; Androgen independent; Second line; Androgen-independent prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cytarabine
• Other Study ID Numbers: SLAP41206