Safety and Effectiveness Study of Docetaxel and ZD1839 Followed by Removal of the Prostate to Treat Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

Phase II Trial of Neoadjuvant Docetaxel and ZD 1839 (Iressa) Followed by Radical Prostatectomy in Patients With High Risk, Locally Advanced Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00242918
• Other study ID #: BRI 8847
• Secondary ID: GIA #161341839US
• Status: Completed
• Phase: Phase 2
• First received: October 20, 2005
• Last updated: February 3, 2012
• Start date: May 2003
• Est. completion date: November 2007

Study information

• Verified date: June 2006
• Source: Benaroya Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and effectiveness of the combination of docetaxel and ZD1839 on destroying prostate cancer before removal of the prostate.

Description:

It is recognized that there is a subset of patients who are at high risk for progression despite aggressive treatment of localized disease at the time of detection. The critical issue is in addressing micrometastatic disease that has already developed prior to diagnosis. This study utilizes daily doses of ZD1839 and weekly docetaxel for two cycles prior to radical prostatectomy.

ZD1839 has demonstrated antiproliferative activity against human tumor xenografts and in coadministration with cytotoxic agents against prostate cell lines (PC-3 and TSU-PRI). The combination of ZD1839 and docetaxel has been reported to be feasible with an acceptable toxicity profile.

This phase II, single center trial is specifically targeting those patients with high-risk adenosarcoma of the prostate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• prostate carcinoma: clinical stage T2b-3 or serum PSA>20 ng/ml or Gleason sum score 8-10.

• clinical T2 patients are eligible if endorectal coil MRI shows T3 disease, or Gleason 4+3 cancer in 5 or more biopsies (minimum of 10 biopsies total required)

• ECOG performance status of 0, 1 or 2

• adequate hematological, liver and renal function

• existing peripheral neuropathy < grade 1

• ability to tolerate oral medications.

Exclusion Criteria:

• Concurrent or prior treatment with radiation, cytotoxic, biologic therapy for prostate cancer

• any major surgery within four weeks

• prior hormonal therapy (except finasteride for obstructive voiding symptoms- -evidence of metastatic disease, confirmed by physical examination, computed tomography of the abdomen and pelvis within 45 days and by bone scan within 60 days of signing informed consent

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• docetaxel

• ZD1839

Locations

Country	Name	City	State
United States	Virginia Mason Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Benaroya Research Institute	AstraZeneca, Sanofi

Country where clinical trial is conducted

United States, 

References & Publications (10)

Barton J, Blackledge G, Wakeling A. Growth factors and their receptors: new targets for prostate cancer therapy. Urology. 2001 Aug;58(2 Suppl 1):114-22. Review. — View Citation

Dreicer R, Klein EA. Preliminary observations of single-agent docetaxel as neoadjuvant therapy for locally advanced prostate cancer. Semin Oncol. 2001 Aug;28(4 Suppl 15):45-8. — View Citation

Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin. 2001 Jan-Feb;51(1):15-36. Erratum in: CA Cancer J Clin 2001 Mar-Apr;51(2):144. — View Citation

Hussain M, Smith DC, El-Rayes BF, Du W, Vaishampayan U, Fontana J, Sakr W, Wood D. Neoadjuvant docetaxel and estramustine chemotherapy in high-risk/locallyadvanced prostate cancer. Urology. 2003 Apr;61(4):774-80. — View Citation

Oh WK, George DJ, Kaufman DS, Moss K, Smith MR, Richie JP, Kantoff PW. Neoadjuvant docetaxel followed by radical prostatectomy in patients with high-risk localized prostate cancer: a preliminary report. Semin Oncol. 2001 Aug;28(4 Suppl 15):40-4. — View Citation

Oh WK, Kantoff PW. Treatment of locally advanced prostate cancer: is chemotherapy the next step? J Clin Oncol. 1999 Nov;17(11):3664-75. Review. — View Citation

Picus J, Schultz M. Docetaxel (Taxotere) as monotherapy in the treatment of hormone-refractory prostate cancer: preliminary results. Semin Oncol. 1999 Oct;26(5 Suppl 17):14-8. — View Citation

Pienta KJ. Preclinical mechanisms of action of docetaxel and docetaxel combinations in prostate cancer. Semin Oncol. 2001 Aug;28(4 Suppl 15):3-7. Review. — View Citation

Simon R. Clinical trial designs for therapeutic cancer vaccines. Cancer Treat Res. 2005;123:339-50. Review. — View Citation

Sirotnak FM, Zakowski MF, Miller VA, Scher HI, Kris MG. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin Cancer Res. 2000 Dec;6(12):4885-92. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the combination of docetaxel and ZD1839 on pathologic complete response (pCR) in radical prostatectomy specimens. Pathological complete response is defined as no microscopic evidence of neoplastic cells in the resected specimen.
Secondary	Evaluate the toxicity of docetaxel and ZD1839 in patients with high risk, locally advanced prostate carcinoma prior to surgical resection
Secondary	Clinical Response
Secondary	Assessment of margin of positivity at surgical resection
Secondary	Evaluate PSA response from baseline and post treatment

External Links

•   Benaroya Research Institute at Virginia Mason is dedicated to discovering the causes of and cures for autoimmune and genetic diseases, to benefit patients with conditions such as diabetes, arthritis, and cancer.
•   Virginia Mason Medical Center is a private, non-profit organization offering a system of integrated health services.