Clinical trial NCT00728663: Docetaxel and Cetuximab in Treating Patients With Metastatic Prostate Cancer
Official title: Docetaxel and Cetuximab in Patients With Docetaxel-resistant Hormone-refractory Prostate Cancer (HRPC). A Multicenter Phase II Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
recurrent prostate cancer
stage IV prostate cancer
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2008-08-06
Enrollment: 35
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: at 12 weeks
measure: Progression-free survival (PFS)
timeFrame: at 24 weeks
Secondary outcomes:
measure: Adverse events
timeFrame: All AEs will be assessed according to NCI CTCAE v3.0.
measure: Prostate-specific antigen (PSA) response (30% and 50% PSA response)
timeFrame: 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)
measure: Tumor assessment of measurable disease according to RECIST criteria
timeFrame: after 12 weeks of treatment, or earlier if clinically indicated
measure: Tumor assessment of bone lesions
timeFrame: at 12 weeks
measure: Overall survival
timeFrame: calculated from registration until death.
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Saint Claraspital AG
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Biel
country: Switzerland
facility: Spitalzentrum Biel
city: Bruderholz
country: Switzerland
facility: Kantonsspital Bruderholz
city: Cham
country: Switzerland
facility: AndreasKlinik Cham Zug
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Freiburg
country: Switzerland
facility: Kantonsspital Freiburg
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Liestal
country: Switzerland
facility: Kantonsspital Liestal
city: Luzerne
country: Switzerland
facility: Kantonsspital, Luzerne
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Regionalspital
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zurich
country: Switzerland
facility: Onkozentrum
city: Zurich
country: Switzerland
facility: Klinik Hirslanden
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Kantonsspital Graubuenden
name: Richard Cathomas, MD
role: STUDY_CHAIR
affiliation: Kantonsspital Graubuenden
name: Roger von Moos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cantonal Hospital of St. Gallen
name: Silke Gillessen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cathomas R, Rothermundt C, von Moos R, et al.: Cetuximab in combination with docetaxel in patients (pts) with metastatic castration resistant (mCRPC) and docetaxel-refractory prostate cancer: A multicenter phase II trial (SAKK 08/07). [Abstract] J Clin Oncol 28 (Suppl 15): A-4666 , 2010.
citation: Cathomas R, Rothermundt C, Klingbiel D, Bubendorf L, Jaggi R, Betticher DC, Brauchli P, Cotting D, Droege C, Winterhalder R, Siciliano D, Berthold DR, Pless M, Schiess R, von Moos R, Gillessen S; Swiss Group for Clinical Cancer Research SAKK. Efficacy of cetuximab in metastatic castration-resistant prostate cancer might depend on EGFR and PTEN expression: results from a phase II trial (SAKK 08/07). Clin Cancer Res. 2012 Nov 1;18(21):6049-57. doi: 10.1158/1078-0432.CCR-12-2219. Epub 2012 Sep 12.