Docetaxel and Prednisone in Treating Patients With Hormone-Refractory Metastatic Prostate Cancer

A Phase III Trial Comparing Docetaxel Every Third Week to Biweekly Docetaxel Monotherapy in Metastatic Hormone Refractory Prostate Cancer Patients - PROSTY Trial

RATIONALE: Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which schedule of docetaxel and prednisone is more effective in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying two different schedules of docetaxel and prednisone to compare how well they work in treating patients with metastatic prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: prednisone

Detailed Description

OBJECTIVES:

Primary

• Compare the time to treatment failure in patients with hormone-refractory metastatic prostate cancer treated with two different schedules of docetaxel in combination with prednisone.

Secondary

• Compare overall survival of patients treated with these regimens.
• Compare the response rate in patients treated with these regimens.
• Compare the safety of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.
• Compare the need for epoetin beta in patients treated with these regimens.
• Determine the effect of epoetin beta on hemoglobin response rate, transfusion rate, and quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center and WHO performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive docetaxel IV over 1 hour on days 1 and 15 and oral prednisone once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive docetaxel IV over 1 hour on day 1 and prednisone once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients who experience anemia (hemoglobin < 11 g/dL) receive epoetin beta subcutaneously once weekly during chemotherapy.

Quality of life is assessed at baseline, every 6 weeks during study treatment, at completion of study treatment, and then every 2 months thereafter.

After completion of study treatment, patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 360 patients (180 per treatment arm) will be accrued for this study within 4 years.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, FIN-00029
    • Helsinki University Central Hospital
  • Kajaani, Finland, 87140
    • Kainuu Central Hospital
  • Kokkola, Finland, 67200
    • Keski-Pohjanmaa Central Hospital
  • Kotka, Finland, 48210
    • Kymenlaakso Central Hospital
  • Lahti, Finland, 15850
    • Tampere University Hospital
  • Oulu, Finland, FIN-90014
    • Oulu University Hospital
  • Pori, Finland, 28500
    • Satakunta Central Hospital
  • Tampere, Finland, 33521
    • Tampere University Hospital
  • Turku, Finland, FIN-20521
    • Turku University Central Hospital
• Ireland
  • Cork, Ireland
    • Bons Secours Hospital
  • Cork, Ireland
    • Mercy University Hospital
  • Dublin, Ireland, 9
    • Beaumont Hospital
  • Dublin, Ireland, 7
    • Mater Misericordiae University Hospital
  • Dublin, Ireland, 24
    • Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
  • Dublin, Ireland, 8
    • St. James's Hospital
  • Galway, Ireland
    • Galway University Hospital
  • Limerick, Ireland, 0009
    • Mid-Western Cancer Centre at Mid-Western Regional Hospital
• Sweden
  • Karlstad, Sweden, 65185
    • Karlstad central Hospital
  • Stockholm, Sweden, S-171 76
    • Karolinska University Hospital - Solna

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 or cytologically confirmed adenocarcinoma of the prostate

  • Metastatic disease by imaging or clinical examination
• Hormone-refractory disease, defined as prostate-specific antigen (PSA) level > 10 µg/L AND rising between 2 sequential measurements
• Testosterone within castration levels by orchiectomy or medical castration comprising luteinizing hormone-releasing hormone (LHRH) analogues

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 11.0 g/dL
• Platelet count ≥ 100,000/mm^3

Hepatic

• ALT and AST ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin normal
• Alkaline phosphatase ≤ 6 times ULN (unless due to the presence of extensive bone disease)
• No serious liver disease

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No ischemic or thromboembolic cardiac disease
• No myocardial infarction within the past 12 months
• No other serious cardiac disease

Pulmonary

• No pulmonary emboli

Immunologic

• No active infection

• No autoimmune disease, including any of the following:

  • Lupus
  • Scleroderma
  • Rheumatoid polyarthritis

Other

• No active peptic ulcer
• No unstable diabetes mellitus
• No contraindication to corticosteroids
• No other malignant disease within the past 5 years except basalioma
• No functional iron deficiency (i.e., transferrin saturation < 20%) that cannot be treated with iron supplementation
• No other serious illness or medical condition

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 2 months since prior recombinant human epoetin alfa or any other erythropoiesis-stimulating drug

Chemotherapy

• At least 3 weeks since prior estramustine

Endocrine therapy

• See Disease Characteristics
• At least 3 weeks since prior antiandrogen treatment

• Concurrent chemical castration with LHRH allowed provided patient has begun treatment prior to study entry

  • No initiation of chemical castration therapy during study treatment

Radiotherapy

• No prior radiotherapy to > 25% of bone marrow
• No prior radioisotope therapy
• Concurrent local palliative radiotherapy for pain allowed

Surgery

• See Disease Characteristics
• At least 4 weeks since prior surgery

Other

• No other prior cytostatic treatment

• Concurrent bisphosphonates allowed provided patient has begun treatment prior to study entry

  • No initiation of bisphosphonates during study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive docetaxel IV over 1 hour on days 1 and 15 and oral prednisone once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: docetaxel; Given in 3- or 4- week courses; Drug: prednisone; Given in 3- or 4- week courses
Experimental: Arm II; Patients receive docetaxel IV over 1 hour on day 1 and prednisone once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: docetaxel; Given in 3- or 4- week courses; Drug: prednisone; Given in 3- or 4- week courses

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time to treatment failure (TTF)

Secondary Outcome Measures

Outcome Measure
Response rate
Overall survival
Safety
Quality of life every 6 weeks until TTF
Use of epoetin beta

Collaborators and Investigators

• Sponsor: Tampere University
• Investigators: Principal Investigator: Pirkko Kellokumpu-Lehtinen, Tampere University Hospital

Publications and helpful links

General Publications

• Kellokumpu-Lehtinen PL, Harmenberg U, Joensuu T, McDermott R, Hervonen P, Ginman C, Luukkaa M, Nyandoto P, Hemminki A, Nilsson S, McCaffrey J, Asola R, Turpeenniemi-Hujanen T, Laestadius F, Tasmuth T, Sandberg K, Keane M, Lehtinen I, Luukkaala T, Joensuu H; PROSTY study group. 2-Weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. Lancet Oncol. 2013 Feb;14(2):117-24. doi: 10.1016/S1470-2045(12)70537-5. Epub 2013 Jan 4.
• Hervonen P, Joensuu H, Joensuu T, Ginman C, McDermott R, Harmenberg U, Nyandoto P, Luukkaala T, Hemminki A, Zaitsev I, Heikkinen M, Nilsson S, Luukkaa M, Lehtinen I, Kellokumpu-Lehtinen PL. Biweekly docetaxel is better tolerated than conventional three-weekly dosing for advanced hormone-refractory prostate cancer. Anticancer Res. 2012 Mar;32(3):953-6. Erratum In: Anticancer Res. 2012 Sep;32(9):4169. multiple author names corrected.

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: November 18, 2005
• First Submitted That Met QC Criteria: November 18, 2005
• First Posted (Estimate): November 21, 2005

Study Record Updates

• Last Update Posted (Estimate): June 26, 2013
• Last Update Submitted That Met QC Criteria: June 25, 2013
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: stage IV prostate cancer; recurrent 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; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Docetaxel; Prednisone
• Other Study ID Numbers: AVENTIS-FIN-1-2003; CDR0000442891 (Registry Identifier: PDQ (Physician Data Query)); FINNISH-URO-OGS-1-2003; PROSTY-FIN-1-2003; ICORG-06-14-Prosty; EU-20891