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

NCT00176293 | Terminated Phase 2

• 1 other identifier: 04-GU-52-B
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

prostate; prostate cancer; doxil; dexamethasone; metastatic; hormone refractory

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects with CR or PR

  evaluated after 2 courses then every other course

Secondary Outcomes (7)

• Hematologic toxicity

  evaluated @ baseline & 3/wk during treatment or until recovery

• Percentage of 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

  continuous throughout study

• QOL

  baseline then every other cycle

• Fraction delivered vs. intended Doxil

  each dose

Study Arms (2)

1

EXPERIMENTAL

dexamethasone

Drug: dexamethasone; Drug: doxorubicin

2

NO INTERVENTION

Interventions

dexamethasone DRUG

oral dexamethasone, 12mg BID on days 1, 2, 3, 4, \& 5 of each 28-day cycle

Also known as: decadron

1

doxorubicin DRUG

Doxorubicin 50mg/m\^2 I.V. on day 5

Also known as: Doxil

1

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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®

Sponsors & Collaborators

• University of Kentucky: lead
• Ortho Biotech, Inc.: collaborator

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

Dexamethasone; Calcium Dobesilate; Doxorubicin; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• John Rinehart, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 15, 2005
• Study Start: October 1, 2005
• Primary Completion: February 1, 2007
• Study Completion: February 1, 2007
• Last Updated: April 21, 2015

Record last verified: 2015-04

Locations

US (1)