Efficacy and Safety Study of Cetuximab or Cetuximab Plus Docetaxel to Treat Prostate Cancer Before Prostatectomy

A Randomized Study of Cetuximab or Cetuximab Plus Docetaxel Followed by Radical Prostatectomy for Patients With Adenocarcinoma of the Prostate

The purpose of this study is to differentiate between the administrations of Cetuximab alone vs. Cetuximab plus Docetaxel in the treatment of non-metastatic prostate cancer before the surgical removal of the prostate.

Study Overview

• Status: Terminated
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: cetuximab; Drug: docetaxel

Detailed Description

With the larger number of men who undergo screening with assays for serum prostate specific antigen, urologists continue to see considerable numbers of patients with locally advanced prostate disease. There is a higher risk of treatment failure in any patient with a tumor that extends through the prostate capsule, more aggressive pathology (Gleason score of 7 or higher), or patients with a PSA of greater than 10 ng/ml. The rationale for adding molecular targeted drugs such as Cetuximab (epithelial growth factor inhibitor), with or without chemotherapy such as Docetaxel, is that such therapy has the potential to demonstrate tumor shrinkage of the prostate and, in addition, micrometastatic cells. Cetuximab alone or Cetuximab plus Docetaxel utilizing the preprostatectomy model, with the adjuvant delivery of Cetuximab for 6 months, will provide data for the following points:

1. demonstration of a PSA response prior to prostatectomy;
2. demonstration whether a change in the natural history, with a delay in the onset of metastatic disease in patients with advanced local prostate cancer, can be achieved;
3. laboratory and tissue correlation to assess changes in proliferative, apoptosis, and pathologic parameters; and
4. metabolic imaging utilizing CT-PET with FDG to assess whether this will be a useful modality in exhibiting a response to therapy, compared with conventional radiographic imaging.

This will provide the basis for future development of neoadjuvant chemotherapy prior to prostatectomy.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Methodist Hospital

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:

• Histologic proof of prostatic adenocarcinoma without evidence of regional and/or distant metastasis, clinical stage T1c or T2a with high grade disease (Gleason's 8-10) on initial biopsy, or clinical stage T2b-T2c with Gleason's grade 7 or above with a PSA ≥ 10ng/ml, or clinical stage T3.
• Recent (< 6 weeks prior to study entry) negative bone scan and MRI of abdomen and pelvis.
• Appropriate surgical candidate for radical prostatectomy and a performance status of < 2 (Zubrod scale).
• Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count > 1,500 and platelet count of > 100,000, adequate hepatic function with a bilirubin < 1.5 mg % and SGPT < 2.5x the upper limits of normal, adequate renal function defined as serum creatinine < 1.5 x ULN.
• Patients must have normal coagulation profile (PT, PTT) and no history of substantial non-iatrogenic bleeding diatheses. Use of anticoagulants is limited to local use only (for control of central line patency).
• Patients must have no history of congestive heart failure or previous MI within the last 12 months.

Exclusion Criteria:

• Previous or current hormonal treatment, chemotherapy, radiation therapy, immunotherapy or other investigational status drug.
• Unable to tolerate transrectal ultrasound.
• Patients who are not appropriate surgical candidates for radical prostatectomy based on the evaluation of co-existent medical diseases and competing causes of death. Patients with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorder are not eligible. Patients with uncontrolled and symptomatic orthostatic hypotension or uncontrolled hypertension are not eligible.
• Patients who are HIV positive or have chronic hepatitis B or C infections are not eligible.
• Patients on oral steroid medications are not eligible.
• Patients with significant arteriosclerotic disease, as defined by a previous arterial bypass claudication limiting activity, or a history of cerebrovascular events within the last year (including TIA) are not eligible.
• Prior severe infusion reaction to a monoclonal antibody.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Data not available PI relocated; No verifiable data available, PI relocated	Drug: cetuximab; No verifiable data available, PI relocated; Other Names: Erbitux; Drug: docetaxel; No verifiable data available, PI relocated; Other Names: Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological response (prostate biopsy vs. prostatectomy specimen pathological evaluation): done pre-treatment vs. after prostatectomy at Week 10	No verifiable data available, PI relocated	during study
Clinical response: digital rectal exam pre-treatment and q 6 months after prostatectomy	No verifiable data available, PI relocated	during study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA response: tested q 3 weeks pre-prostatectomy and q 6 months post-prostatectomy	No verifiable data available, PI relocated	during study
Correlation with MRI and nuclear imaging: scans pre-treatment vs. Week 10 before surgery and yearly when PSA > 0.3	No verifiable data available, PI relocated	during study
Correlation with metabolic imaging (PET with FDG): scans pre-treatment vs. Week 10 before surgery	No verifiable data available, PI relocated	during study
Correlation with serum and plasma for antiangiogenic factors: tested q 3 weeks pre-prostatectomy	No verifiable data available, PI relocated	during study

Collaborators and Investigators

• Sponsor: The Methodist Hospital Research Institute
• Collaborators: Bristol-Myers Squibb; Eli Lilly and Company
• Investigators: Principal Investigator: Robert J Amato, DO, Baylor College of Medicine - Methodist Hospital

Publications and helpful links

General Publications

• Prewett M, Rockwell P, Rockwell RF, Giorgio NA, Mendelsohn J, Scher HI, Goldstein NI. The biologic effects of C225, a chimeric monoclonal antibody to the EGFR, on human prostate carcinoma. J Immunother Emphasis Tumor Immunol. 1996 Nov;19(6):419-27. doi: 10.1097/00002371-199611000-00006.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: March 14, 2007
• First Submitted That Met QC Criteria: March 14, 2007
• First Posted (Estimate): March 15, 2007

Study Record Updates

• Last Update Posted (Estimate): March 17, 2016
• Last Update Submitted That Met QC Criteria: March 15, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Prostate cancer; Neoadjuvant; Adenocarcinoma of the Prostate; Pre-Prostatectomy
• 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; Antineoplastic Agents, Immunological; Docetaxel; Cetuximab
• Other Study ID Numbers: HMRI IRB#0206-0027; E-VS-ET-2006 (Other Identifier: Principal Investigator)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO