Docetaxel and Cetuximab in Treating Patients With Metastatic Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of prostate cancer by blocking blood flow to the tumor. Giving docetaxel together with cetuximab may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects of giving docetaxel together with cetuximab and to see how well it works in treating patients with metastatic prostate cancer.

Detailed Description
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OBJECTIVES: To assess the efficacy and safety of docetaxel and cetuximab in patients with docetaxel-resistant hormone-refractory prostate cancer OUTLINE: This is a multicenter study. Patients receive cetuximab IV once weekly and docetaxel IV on day 1 (3-week courses) or on days 1, 8, and 15 (4-week courses). Treatment repeats every 3 weeks for up to 8 courses or every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

Official Title
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Docetaxel and Cetuximab in Patients With Docetaxel-resistant Hormone-refractory Prostate Cancer (HRPC). A Multicenter Phase II Trial

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Metastatic adenocarcinoma of the prostate Must have received one of the following treatment schedules for at least 12 weeks prior to study therapy: Docetaxel 75 mg/m^2 on day 1 of a 21-day course Docetaxel 35 mg/m^2 on days 1, 8, and 15 of a 28-day course Must demonstrate hormone-resistance, defined as tumor progression after orchiectomy or during treatment with hormonal agents (i.e., luteinizing hormone-releasing hormone [LHRH] agonists) Elevated prostate-specific antigen (PSA) > 2 ng/mL and PSA progression after at least 12 weeks treatment with docetaxel/prednisone, within 90 days after discontinuation of docetaxel/prednisone treatment, under continued hormonal treatment (i.e., LHRH agonists or orchiectomy), and meets 1 of the following criteria for PSA progression: PSA increase of ≥ 25% above the nadir PSA increase of ≥ 25% above the baseline if no decrease has been observed The increase is a minimum of 2 ng/mL, and it is confirmed 1 week later No presence or history of CNS metastases PATIENT CHARACTERISTICS: WHO performance status 0-2 Neutrophils ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT ≤ 2.5 times ULN Creatinine clearance ≥ 30 mL/min Patient compliance and geographic proximity allow proper staging and follow-up Peripheral neuropathy < grade 2 No prior malignancy within the past 5 years with the exception of localized nonmelanoma skin cancer or Ta or Tis bladder cancer No known hypersensitivity to trial drugs or any of their components No serious underlying medical condition that, in the judgment of the investigator, would preclude the patient's ability to participate in the trial (e.g., active autoimmune disease, uncontrolled or acute severe infection, or uncontrolled diabetes) No psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, or interfering with oral drug intake compliance PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 2 weeks since prior radiotherapy More than 6 weeks since prior treatment with antiandrogens (i.e., flutamide or bicalutamide) No prior chemotherapy other than docetaxel for metastatic prostate cancer No other concurrent experimental drugs or other anticancer therapy Concurrent bisphosphonates and LHRH agonists allowed provided these medications started at least 2 months prior to study therapy No treatment in a clinical trial within the past 30 days No prior treatment with drugs interacting with epidermal growth factor receptor (i.e., cetuximab, panitumumab, gefitinib, erlotinib hydrochloride, or multi-tyrosine kinase inhibitors) No concurrent drugs that, according to the Swissmedic-approved product information, are contraindicated for use with the trial drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm: Cetuximab and Docetaxel<br>Cetuximab: 400 mg/m2 initial dose on day 1, then 250 mg/m2 weekly starting on day 8 and Docetaxel: 75 mg/m2 day 1 of a 21 day cycle or 35 mg/m2 day 1,8,15 of a 28 day cycle --- for max. 24 weeks or until progression or unacceptable toxicity --- | Biological: cetuximab<br>* Cetuximab: 400 mg/m2 initial dose on day 1, then 250 mg/m2 weekly starting on day 8 --- for max. 24 weeks or until progression or unacceptable toxicity ---<br>* Other names: Erbitux;Drug: docetaxel<br>* 75 mg/m2 day 1 of a 21 day cycle or 35 mg/m2 day 1,8,15 of a 28 day cycle --- for max. 24 weeks or until progression or unacceptable toxicity ---<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | at 12 weeks | 
| Progression-free survival (PFS) |  | at 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | All AEs will be assessed according to NCI CTCAE v3.0. | 
| Prostate-specific antigen (PSA) response (30% and 50% PSA response) |  | is defined as a decrease in PSA level of at least 50% (compared to baseline PSA) confirmed after 3-4 weeks (according to the PSA working group consensus criteria) | 
| Tumor assessment of measurable disease according to RECIST criteria |  | after 12 weeks of treatment, or earlier if clinically indicated | 
| Tumor assessment of bone lesions |  | at 12 weeks | 
| Overall survival |  | calculated from registration until death. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, recurrent prostate cancer, stage IV prostate cancer