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

Sponsors and Collaborators:	University of Kentucky Ortho Biotech, Inc.
Information provided by:	University of Kentucky
ClinicalTrials.gov Identifier:	NCT00176293

Purpose

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.

Condition	Intervention	Phase
Prostate Cancer	Drug: dexamethasone Drug: doxorubicin	Phase II

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	A Randomized Phase II Trial of Doxil With or Without Dexamethasone in Treatment of Patients With Metastatic Hormone Refractory Prostate Cancer

Further study details as provided by University of Kentucky:

Primary Outcome Measures:

Percentage of subjects with CR or PR [ Time Frame: evaluated after 2 courses then every other course ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Enrollment:	2
Study Start Date:	October 2005
Study Completion Date:	February 2007
Primary Completion Date:	February 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental dexamethasone	Drug: dexamethasone oral dexamethasone, 12mg BID on days 1, 2, 3, 4, & 5 of each 28-day cycle Drug: doxorubicin Doxorubicin 50mg/m^2 I.V. on day 5
2: No Intervention	Drug: doxorubicin Doxorubicin 50mg/m^2 I.V. on day 5

Detailed Description:

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.

Eligibility

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

Criteria

Inclusion Criteria:

Patients with metastatic hormone refractory prostate cancer as defined by resistance to both ablative therapy (with either LHRH agonists or orchiectomy) & anti-androgens.
Patients must have symptoms related to disease.
Patients must have PS 0,1,2 (ECOG).
Patients must have measurable disease (RECIST) or PSA > 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.
Patients must have a left ventricular ejection fraction (LVEF) 50% by echocardiogram
Patients must have failed to respond to discontinuation of anti-androgens.
No previous therapy with anti-androgens, corticosteroids or estrogens in the last 4 weeks.
Previous radiation therapy is allowed if completed at least 4 weeks prior to study entry & therapy was cumulatively administered to </= 25% of bone marrow.
Patients must be >18 years of age
Patients must have an expected survival of at least 4 months.
Patients must have the ability to understand & the willingness to sign a written informed consent document.
Patients must be willing to use adequate contraceptive method during treatment and for 3 months after completing treatment.

Exclusion Criteria:

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.
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.
Patients requiring any non study corticosteroids for any reason are excluded.
Patients who have received previous chemotherapy.
A history of cardiac disease with New York Heart Class II or greater, or clinical evidence of congestive heart failure.
Patients may not be receiving any other investigational agents or have participated in any investigational drug study within 4 weeks preceding initiation of treatment.
Major surgery within 4 weeks prior to study treatment start, or lack of complete recovery from major surgery.
Patients with a lack of physical integrity of the upper gastrointestinal tract or those who have malabsorption syndrome or inability to swallow tablets.
History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCL or the components of Doxil®

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00176293

Locations

United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536

Sponsors and Collaborators

University of Kentucky

Ortho Biotech, Inc.

Investigators

Principal Investigator:

John Rinehart, MD

University of Kentucky

More Information

Responsible Party:	University of Kentucky ( John Rinehart, M.D., Principal Investigator )
Study ID Numbers:	04-GU-52-B
Study First Received:	September 13, 2005
Last Updated:	January 7, 2008
ClinicalTrials.gov Identifier:	NCT00176293
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Kentucky:

prostate
prostate cancer
doxil

dexamethasone
metastatic
hormone refractory

Study placed in the following topic categories:

Dexamethasone
Prostatic Diseases
Genital Neoplasms, Male
Urogenital Neoplasms

Genital Diseases, Male
Prostatic Neoplasms
Doxorubicin
Dexamethasone acetate

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Antibiotics, Antineoplastic
Glucocorticoids

Hormones
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Autonomic Agents
Therapeutic Uses
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009