Randomized Phase II Trial of Doxil With or Without Dexamethasone for Metastatic Hormone Refractory Prostate Cancer

This study has been terminated.
(Slow accrual)
Sponsor:
Collaborator:
Ortho Biotech, Inc.
Information provided by:
University of Kentucky
ClinicalTrials.gov Identifier:
NCT00176293
First received: September 13, 2005
Last updated: January 7, 2008
Last verified: January 2008

September 13, 2005
January 7, 2008
October 2005
February 2007   (final data collection date for primary outcome measure)
Percentage of subjects with CR or PR [ Time Frame: evaluated after 2 courses then every other course ] [ Designated as safety issue: No ]
•% subjects with CR or PR: evaluated after 2 courses then every other course.
Complete list of historical versions of study NCT00176293 on ClinicalTrials.gov Archive Site
  • Hematologic toxicity [ Time Frame: evaluated @ baseline & 3/wk during treatment or until recovery ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with >/= Grade 3 hematopoietic & non-hematopoietic toxicities [ Time Frame: labs evaluated @ baseline & 3/wk during treatment or until recovery; toxicity evaluated through treatment or until resolved ] [ Designated as safety issue: Yes ]
  • Clinical non-hematologic & hematologic toxicity [ Time Frame: continuous throughout study ] [ Designated as safety issue: Yes ]
  • QOL [ Time Frame: baseline then every other cycle ] [ Designated as safety issue: No ]
  • Fraction delivered vs. intended Doxil [ Time Frame: each dose ] [ Designated as safety issue: No ]
  • Cytokines [ Time Frame: evaluated days 1, 5, 8 every other cycle ] [ Designated as safety issue: Yes ]
  • Survival [ Time Frame: evaluated through study ] [ Designated as safety issue: No ]
  • • Hematologic toxicity: evaluated @ baseline & 3/wk during treatment or until recovery.
  • • % subjects with >/= Grade 3 hematopoietic & non-hematopoietic toxicities: labs evaluated @ baseline & 3/wk during treatment or until recovery; toxicity evaluated through treatment or until resolved.
  • • Clinical non-hematologic & hematologic toxicity: evaluate incidence of stomatitis, diarrhea, palmar plantar erythrodysesthesia, # hospital days febrile neutropenia, transfusions & bleeding, # days outpatient antibiotics -all assessed through study.
  • • Survival & QOL: QOL evaluated at baseline then every other cycle; survival evaluated through study.
  • • Fraction delivered vs. intended Doxil: evaluate each dose.
  • • cytokines: evaluated days 1, 5, 8 every other cycle.
Not Provided
Not Provided
 
Randomized Phase II Trial of Doxil With or Without Dexamethasone for Metastatic Hormone Refractory Prostate Cancer
A Randomized Phase II Trial of Doxil With or Without Dexamethasone in Treatment of Patients With Metastatic Hormone Refractory Prostate Cancer

The primary objective of this study is to assess disease response to Doxil in patients with hormone refractory prostate cancer with or without dexamethasone pre-treatment.

Study Design:

We will perform an open labeled, parallel, randomized phase II study using a two-stage design to determine if there is sufficient anti-tumor activity in either arm to warrant further study. Assumptions made in this study: an unacceptable overall response rate is </= 10% & we will pursue further study if the overall response rate is >/= 30%. Fifteen patients will be randomized in the first phase (to both Arm 1 and Arm 2). No further patients will be accrued if <2/15 responses are noted in a given arm. Ten additional patients will be enrolled if >/= 2/15 responses are observed. If there are >/= 5/25 responses then further studies will be pursued with that regimen. We will determine the overall incidence & severity of toxicities in both arms.

Treatment:

Arm 1: Doxil: Dose: 50 mg/m2, IV (in the vein) on day 5 of each 28 day cycle. Arm 2: Doxil: Dose: 50 mg/m2, IV (in the vein) on day 5 of each 28 day cycle. Arm 1 only: Dexamethasone: Dose: 12 mg twice a day by mouth on days 1, 2, 3, 4, 5 of each 28 day cycle.

Number of Cycles for both Arm 1 & 2: until progression or unacceptable toxicity develops.

Primary Objectives:

To assess the anti-tumor activity of Doxil by assessing response rates in patients with hormone refractory prostate cancer with or without dexamethasone pre-treatment.

Secondary Objectives:

To assess and estimate in patients with hormone refractory prostate cancer treated with Doxil with or without pre-treatment dexamethasone: 1) overall survival 2) toxicity, 3) quality of life parameters, 4) dose intensity administered in both treatment groups.

Study Design:

We will perform an open labeled, parallel, randomized phase II study using a two-stage design to determine if there is sufficient anti-tumor activity in either arm to warrant further study. Assumptions made in this study: an unacceptable overall response rate is </= 10% and we will pursue further study if the overall response rate is >/= 30%. The overall response rate for this study will be based on the total number of responses observed defined as: complete responses + partial responses (both by RECIST)+biochemical responses (in patients with no measurable target lesions a >/= 50% decrease in PSA for >/= 4 weeks). Fifteen patients will be randomized in the first phase (to both Arm 1 and Arm 2). No further patients will be accrued if <2/15 responses are noted in a given arm. Ten additional patients will be enrolled if >/= 2/15 responses are observed. If there are >/= 5/25 responses then further studies will be pursued with that regimen. We will determine the overall incidence and severity of toxicities in both arms.

Treatment:

Arm 1: Doxil: Dose: 50 mg/m2, IV. Frequency: day 5 of each 28 day cycle. Arm 2: Doxil: Dose: 50 mg/m2, IV. Frequency: day 5 of each 28 day cycle. Arm 1 only: Dexamethasone: Dose: 12 mg bid po. Frequency: days 1,2,3,4,5 of each 28 day cycle.

Number of Cycles for both Arm 1 and 2: until progression or unacceptable toxicity develops.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: dexamethasone
    oral dexamethasone, 12mg BID on days 1, 2, 3, 4, & 5 of each 28-day cycle
    Other Name: decadron
  • Drug: doxorubicin
    Doxorubicin 50mg/m^2 I.V. on day 5
    Other Name: Doxil
  • Experimental: 1
    dexamethasone
    Interventions:
    • Drug: dexamethasone
    • Drug: doxorubicin
  • No Intervention: 2
    Intervention: Drug: doxorubicin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
2
February 2007
February 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Patients with metastatic hormone refractory prostate cancer as defined by resistance to both ablative therapy (with either LHRH agonists or orchiectomy) & anti-androgens.
  2. Patients must have symptoms related to disease.
  3. Patients must have PS 0,1,2 (ECOG).
  4. Patients must have measurable disease (RECIST) or PSA > 5.
  5. Patients must have adequate organ function as defined as follows: leukocytes >/= 3,000/mm3, absolute neutrophil count >/= 1,500/mm3, hemoglobin >/= 8.0g/dl, platelets >/= 100,000/mm3, serum creatinine </= 2.5 mg/dl. Bilirubin must be </= 2 fold above ULN. Liver transaminases (SGOT and/or SGPT) may be up to 2.5 x institutional ULN if alkaline phosphatase is </= ULN or alkaline phosphatase may be up to 4 x ULN if transaminases are </= ULN.
  6. Patients must have a left ventricular ejection fraction (LVEF) 50% by echocardiogram
  7. Patients must have failed to respond to discontinuation of anti-androgens.
  8. No previous therapy with anti-androgens, corticosteroids or estrogens in the last 4 weeks.
  9. Previous radiation therapy is allowed if completed at least 4 weeks prior to study entry & therapy was cumulatively administered to </= 25% of bone marrow.
  10. Patients must be >18 years of age
  11. Patients must have an expected survival of at least 4 months.
  12. Patients must have the ability to understand & the willingness to sign a written informed consent document.
  13. Patients must be willing to use adequate contraceptive method during treatment and for 3 months after completing treatment.

Exclusion Criteria:

  1. Patients with previous history of cancer are excluded unless they have had curative treatment completed >/= 5 years prior to entry onto study or had 1 of the following: in situ carcinoma (any location), basal cell carcinoma, or non-metastatic squamous cell carcinoma of the skin.
  2. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, uncontrolled diabetes mellitus, or psychiatric illness/social situations that would limit compliance with study requirements or the ability to provide informed consent.
  3. Patients requiring any non study corticosteroids for any reason are excluded.
  4. Patients who have received previous chemotherapy.
  5. A history of cardiac disease with New York Heart Class II or greater, or clinical evidence of congestive heart failure.
  6. Patients may not be receiving any other investigational agents or have participated in any investigational drug study within 4 weeks preceding initiation of treatment.
  7. Major surgery within 4 weeks prior to study treatment start, or lack of complete recovery from major surgery.
  8. Patients with a lack of physical integrity of the upper gastrointestinal tract or those who have malabsorption syndrome or inability to swallow tablets.
  9. History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCL or the components of Doxil®
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00176293
04-GU-52-B
Not Provided
John Rinehart, M.D., Principal Investigator, University of Kentucky
University of Kentucky
Ortho Biotech, Inc.
Principal Investigator: John Rinehart, MD University of Kentucky
University of Kentucky
January 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP