Chemotherapy, Hormone Therapy, and Radiation Therapy in Treating Patients With Locally Advanced Prostate Cancer

Phase II Study Of Neo-Adjuvant Paclitaxel, Estramustine And Carboplatin (TEC) Plus Androgen Ablation Prior To Radiation Therapy In Patients With Poor Prognosis Localized Prostate Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin or leuprolide may stop the adrenal glands from producing androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy, hormone therapy, and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying giving chemotherapy together with hormone therapy and radiation therapy in treating patients with locally advanced prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: estramustine; Drug: paclitaxel; Radiation: radiation therapy; Drug: leuprolide or goserelin acetate

Detailed Description

OBJECTIVES:

• Determine the feasibility and safety of paclitaxel, estramustine, carboplatin, and androgen ablation followed by radiotherapy in patients with poor-prognosis locally advanced prostate cancer.
• Determine the progression-free survival and time to prostate specific antigen failure in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive paclitaxel IV over 1 hour once weekly; oral estramustine three times a day, five days a week; and carboplatin IV over 1 hour once monthly. Treatment repeats every 4 weeks for 4 courses.

Patients also receive gonadotropin-releasing hormonal therapy comprising either goserelin subcutaneously or leuprolide intramuscularly once monthly. Treatment repeats every 4 weeks for 6 courses.

After the completion of chemotherapy, patients undergo radiotherapy once daily on weeks 17-24.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1.5 years.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
    • Washington, District of Columbia, United States, 20307-5001
      • Walter Reed Army Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Veterans Affairs Medical Center - Baltimore
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Cancer Center - University Campus
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Saint Luke's Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • Oswego, New York, United States, 13126
      • Oswego Hospital
    • Syracuse, New York, United States, 13210
      • Veterans Affairs Medical Center - Syracuse
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
    • Syracuse, New York, United States, 13215
      • Community General Hospital of Greater Syracuse
    • Syracuse, New York, United States, 13057
      • CCOP - Hematology-Oncology Associates of Central New York
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Kinston, North Carolina, United States, 28501
      • Lenoir Memorial Cancer Center
    • Wilson, North Carolina, United States, 27893-3428
      • Wilson Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis Cancer Center at Roper Hospital
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29601
      • Bon Secours St. Francis Health System
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical 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

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate with one of the following prognostic factors:

  • Tx N0, baseline prostate specific antigen (PSA) greater than 20 ng/mL, and Gleason score at least 7
  • T3b-4 N0, any baseline PSA, and any Gleason score
• No pelvic lymph node disease requiring pelvic radiotherapy
• No metastatic disease by bone scan, CT scan, or MRI

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 1.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No significant cardiovascular disease
• No New York Heart Association class III or IV congestive heart failure
• No active angina pectoris
• No myocardial infarction within the past 6 months
• No history of hemorrhagic or thrombotic cerebral vascular accident
• No deep vein thrombosis within the past 6 months

Pulmonary:

• No pulmonary embolism within the past 6 months

Other:

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy for prostate cancer
• No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy:

• No prior chemotherapy for prostate cancer
• No other concurrent anticancer chemotherapy

Endocrine therapy:

• No more than 6 weeks of prior androgen deprivation therapy
• No other concurrent anticancer hormonal therapy except steroids for adrenal failure and/or hormones for nondisease-related conditions (e.g., insulin for diabetes)

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy for prostate cancer
• No other concurrent anticancer radiotherapy

Surgery:

• At least 4 weeks since prior major surgery

Other:

• No prior alternative therapy (e.g., PC-SPES) for prostate cancer
• No concurrent alternative medicine (e.g., PC-SPES or saw palmetto) or large quantities of vitamins
• No other concurrent anticancer therapy

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: Neo-Adj ChemoTx + ablation prior to RT; Patients with localized high-risk prostate cancer were treated with 4 cycles (16 weeks) of continuous weekly paclitaxel at 80 mg/m^2 intravenously with estramustine at 280 mg orally 3 times a day for 5 days a week and carboplatin (area under the curve of 6) on Day 1 of every cycle followed by 3-dimensional conformal or intensity-modulated radiotherapy (total dose of 77.4 gray [Gy] in 1.8-Gy fractions). All patients received androgen deprivation therapy with either goserelin acetate at 3.6 mg subcutaneously or leuprolide acetate at 7.5 mg intramuscularly monthly for 6 months starting at Day 1 of therapy.

Drug: carboplatin; AUC=6 week one of each 4 week cycle; Drug: estramustine; 2 tablets tid PO 5 of 7 days per week each 4 week cycle; Drug: paclitaxel; 80 mg/sq m IV infusion over 1 hour weekly for ea 4 week cycle; Radiation: radiation therapy; 77.4 Gy in 1.8 Gy fractions; Drug: leuprolide or goserelin acetate; 7.5 mg IM injection once every 4 weeks for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	Patients were evaluated for acute toxicities defined as grade 3 or greater cardiovascular (including venous thrombosis), gastrointestinal, or genitourinary toxicity occurring during the period starting from treatment initiation until 90 days or less after the completion of radiotherapy. The same toxicity measures were monitored at >90 days after the completion of radiotherapy.	90 days and 1 year post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Prostate-specific Antigen Failure	PSA progression was defined in 2 ways. The CALGB PSA progression was defined as 2 consecutive rises in PSA with a rise of at least 0.2 ng/mL and above 1.0 ng/mL after radiation therapy; the date of PSA failure is taken as the midpoint between the last PSA before the rise and the first of the 2 PSAs that documented the rise. In addition, PSA progression was used according to the American Society for Therapeutic Radiology and Oncology 1996 (ASTRO) criteria and defined as 3 consecutive rises in PSA after radiation therapy. The date of PSA failure was taken as the midpoint between the time of the lowest PSA measure after irradiation and the first of the 3 consecutive rises.	PSA was measured every 4 weeks during chemotherapy, at least every 12 weeks post radiation for 2 years, and every 6 months thereafter until PSA failure date (Up to 5.5 years).
Progression-free Survival (PFS)	PFS was defined as the time between treatment initiation and the date of disease progression (PSA, bone, tumor) or death, whichever occurred first. PSA progression is defined as 2 consecutive rising PSAs (a rise of at least 0.2 ng/mL) above 1.0 ng/mL.	registration to progression, up to 5.5 years from registration

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: William K. Kelly, DO, Yale University

Publications and helpful links

General Publications

• Kelly WK, Halabi S, Elfiky A, Ou SS, Bogart J, Zelefsky M, Small E; Cancer Leukemia Group B. Multicenter phase 2 study of neoadjuvant paclitaxel, estramustine phosphate, and carboplatin plus androgen deprivation before radiation therapy in patients with unfavorable-risk localized prostate cancer: results of Cancer and Leukemia Group B 99811. Cancer. 2008 Dec 1;113(11):3137-45. doi: 10.1002/cncr.23910.

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: June 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: stage III prostate cancer; adenocarcinoma of the prostate
• 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; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Carboplatin; Paclitaxel; Leuprolide; Goserelin; Estramustine
• Other Study ID Numbers: CALGB-99811; U10CA031946 (U.S. NIH Grant/Contract); CDR0000068632 (Registry Identifier: NCI Physician Data Query)