Study of Taxotere and Doxil to Treat Advanced Androgen-Independent Prostate Cancer

Phase I/II Study of Docetaxel (Taxotere) in Combination With Doxorubicin HCI Liposome Injection (Doxil) in Advanced Androgen-Independent Prostate Cancer (AIPC)

This clinical research study is being done because there is no effective treatment for advanced androgen-independent prostate cancer. This study will determine if the combination of medications (Taxotere and Doxil) are effective in this kind of cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Taxotere; Drug: Doxil

Detailed Description

Each cycle of treatment will consist of four weeks. The 2 types of medicines are given intravenously (in a vein). Doxil is given on the first day of each cycle. Taxotere is given once a week for the first 3 weeks of each cycle. This is followed by a week of rest until the next cycle starts. Treatment is given on an outpatient basis and hospitalization is not anticipated.

Prior to entry on this study, "screening" tests are performed to determine eligibility to participate. This will involve a complete history and physical examination, vital signs, pain assessment, blood tests including CBC (complete blood count), serum chemistry, and PSA (prostate specific antigen), x-rays (chest x-ray, possible plain films of bones if there are abnormal findings on bone scan for clarification), computerized tomography (CT) scans of the abdomen and pelvis, bone scans, a MUGA scan or 2-D echocardiogram, and a quality of life questionnaire.

After treatment starts the following tests are done to regularly monitor for beneficial and toxic effect of the treatment:

Every week: blood tests.

Every month: physical examination, weight, vital signs (blood pressure, respiration, temperature and heart rate) and PSA test.

Every 2 months: pain assessment, quality of life questionnaire, x-rays (chest x-ray and possible pain films of bones if positive findings are seen on bone scan), computerized tomography (CT) scans (abdomen and pelvis) and bone scans.

Participants may continue with any procedures that are part of their regular cancer care. It is anticipated that participants will be in the study for a minimum of 2 months and as long as they are benefiting from the treatment.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center

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:

• Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate.
• Androgen-independent disease progression, as shown by:
• A castrate testosterone level of < 40 ng/dl (this measurement is required only for patients treated with medical testicular suppression). If testicular suppression is achieved medically, treatment to maintain castrate levels of testosterone must be applied continuously.
• A PSA level of at least 4 ng/ml, and rising (with an absolute change of at least 1 ng/ml) on two consecutive measurements at least 2 weeks apart prior to study entry.
• Patients must be off anti-androgens such as flutamide (Eulexin) or nilutamide (Nilandron) for at least four weeks, and six weeks for bicalutamide (Casodex), without evidence of response; or have evidence of progression since anti-androgen withdrawal.
• None or one previous cytotoxic therapy is allowed. (For this study, a combination of agents given at the same period of time is considered one chemotherapy treatment)
• Age > 18 years of age.
• Life expectancy of greater than 12 weeks.
• ECOG performance status 0, 1 or 2 (Karnofsky >50%; see Appendix B).

• Patients must have adequate bone marrow function as defined below:

  • absolute neutrophil count > 1,500/ul
  • platelets > 100,000/ul
  • hemoglobin > 8 g/dl

• Patients must have adequate liver function as defined below:

  • total bilirubin normal, albumin > 3.0 g/dl, and no ascites
  • AST(SGOT) and ALT(SGPT) and Alkaline Phosphatase must be within the range allowing for eligibility
• Patients must have adequate renal function as defined by a creatinine < 2.5 mg/dl or a creatinine clearance > 30 mL/min (measured or estimated by the Cockroft formula) for patients with creatinine levels above 2.5 mg/dl
• Patients must have recovered from acute toxicities from chemotherapy or radiotherapy administered prior to entering this study. Alopecia may not be resolved and peripheral neuropathy (grade 1) may be present.
• Patients must have a MUGA scan or 2-d echocardiogram indicating an ejection fraction of > 50% within 42 days prior to first dose of study drug. The method used at baseline must be used for later monitoring.
• Patients with reproductive potential must use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment.
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients who have had two or more prior chemotherapy treatment(s) (For this study, a combination of agents given at the same period of time is considered one chemotherapy treatment).
• Patients receiving any other investigational agent(s).
• Patients with symptomatic brain metastases or actively receiving any therapy for brain metastasis (because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events).
• Active second malignancy in the last 5 years except for non-melanoma skin cancer or carcinoma-in-situ.
• History of cardiac disease, with New York Heart Association Class II or greater, or clinical evidence of congestive heart failure.
• History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCL, the components of Doxil, docetaxel or other drugs formulated with polysorbate 80.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

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: Taxotere and Doxil; Treatment will be repeated every 28 days. Taxotere is administered on days 1, 8 and 15 (rate: 1 hour). Dose levels 1, 2 and 3 (mg/m2 i.v.) are 25, 25 and 30, respectively. Treatment will be administered on an outpatient basis. Treatment will be repeated every 28 days. Doxil is administered on day 1 (rate: 1mg/min). Dose levels 1, 2 and 3 (mg/m2 i.v.) are 25, 30 and 30, respectively.

Drug: Taxotere; Treatment will be administered on an outpatient basis. Treatment will be repeated every 28 days. Taxotere is administered on days 1, 8 and 15 (rate: 1 hour). Dose levels 1, 2 and 3 (mg/m2 i.v.) are 25, 25 and 30, respectively.; Drug: Doxil; Treatment will be administered on an outpatient basis. Treatment will be repeated every 28 days. Doxil is administered on day 1 (rate: 1mg/min). Dose levels 1, 2 and 3 (mg/m2 i.v.) are 25, 30 and 30, respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose and Toxicity Profile	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Data not analyzed, PI left institution	7 years

Collaborators and Investigators

• Sponsor: University of Louisville
• Collaborators: James Graham Brown Cancer Center
• Investigators: Principal Investigator: Damian Laber, MD, James Graham Brown Cancer Center

Publications and helpful links

General Publications

• Laber DA, Eatrides J, Jaglal MV, Haider M, Visweshwar N, Patel A. A phase I/II study of docetaxel in combination with pegylated liposomal doxorubicin in metastatic castration-resistant prostate cancer. Med Oncol. 2020 Sep 26;37(10):95. doi: 10.1007/s12032-020-01420-7.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: April 4, 2007
• First Submitted That Met QC Criteria: April 4, 2007
• First Posted (Estimate): April 5, 2007

Study Record Updates

• Last Update Posted (Actual): October 30, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Prostate Cancer; Doxil; Taxotere; AIPC; Advanced Androgen-Independent Prostate Cancer; Androgen Independent
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: IRB# 575-03