Phase 2 N=73 Treatment

Docetaxel, Thalidomide, Prednisone, and Bevacizumab to Treat Metastatic Prostate Cancer

Prostatic Neoplasms

Bottom Line

View on ClinicalTrials.gov: NCT00089609 ↗

Enrolled (actual)

Serious AEs

71.2%

Results posted

Nov 2012

Primary outcome: Primary: Number of Participants Who Had a Prostate-specific Antigen (PSA) Response — 52 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Docetaxel (Drug); Thalidomide (Drug); Prednisone (Drug); bevacizumab (Biological); polymorphism analysis (Genetic); immunoenzyme technique (Other); laboratory biomarker analysis (Other); pharmacological study (Other)
Age: Adult, Older Adult · 18+ yrs
Sex: Male
Sponsor: National Cancer Institute (NCI)
Primary completion: Dec 2011

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants Who Had a Prostate-specific Antigen (PSA) Response	52	—
PRIMARY Immune Response	—	—
SECONDARY Number of Participants With Adverse Events	60; 13	—
SECONDARY Time to Progression Using Bubley Criteria	18.3	—
SECONDARY Disease Progression by Clinical and Radiographic Criteria Without the Use of Prostate-Specific Antigen (PSA)	2; 19; 11; 1	—
SECONDARY Number of Participants Who Died After a Follow Up of 34 Months Following Treatment	38	—
SECONDARY Plasma Concentrations of Docetaxel and Thalidomide and Clinical Activity or Toxicity	—	—
SECONDARY Number of Participants With a Significant Increase in Circulating Apoptotic Endothelial Cell (CAEC) Level	14; 0	.02 sig
SECONDARY Analyze the Patients Genotype With Regard to Cytochrome P450 2C19 Polymorphism and Correlate That With Pharmacokinetics and Efficacy	—	—
SECONDARY Usefulness of Dynamic Magnetic Resonance Imaging (MRI) to Monitor the Progression of Bony and Soft Tissue Disease in Metastatic Prostate Cancer	—	—
SECONDARY Changes in the Molecular Markers of Angiogenesis (Including, But Not Limited to Serum and Urine Vascular Endothelial Growth Factor (VEGF)) Before and After Administration of Docetaxel, Prednisone, Thalidomide and Bevacizumab	—	—

Summary

This is a Phase II study of docetaxel, bevacizumab, prednisone and thalidomide in patients with androgen independent metastatic prostate cancer who are previously untreated with chemotherapy. The primary objective of this study is to determine if the combination of docetaxel, thalidomide and bevacizumab is able to be associated with a sufficiently high proportion of patients with a prostate-specific antigen (PSA) response to be worthy of further investigation in metastatic prostate cancer. We will also be looking at multiple secondary endpoints. These will include possible pharmacokinetic interactions among the study agents, potential correlation between patient genotype and efficacy of treatment. We will also be looking for circulating tumor cells in blood before and after treatment. Additionally we will be monitoring the tolerability of the regimen and survival duration as endpoints as well. We hope to use this trial to build on the promising results seen in our thalidomide/docetaxel protocol where there was a significant PSA decline and a trend toward survival benefit.

Eligibility Criteria

INCLUSION CRITERIA:

Androgen-independent metastatic adenocarcinoma of the prostate defined as progressive metastatic disease while on gonadotropin releasing hormone (GnRH) agonists or post surgical castration

Histopathological documentation of prostate cancer confirmed in the National Cancer Institute (NCI) Laboratory of Pathology at the National Institutes of Health, the Pathology Department at Walter Reed Medical Center or the Pathology Department at National Naval Medical Center, prior to starting this study. In addition, patients whose slides are lost or unavailable will be eligible for the study if they provide documentation of prostate cancer and if they meet criteria of clinically progressive prostate cancer as outlined in section 3.1.1.3.

Clinically progressive prostate cancer documented prior to entry. Progression must be documented by at least one of the following parameters:

Two consecutively rising prostate-specific antigen (PSA) levels. The first rising PSA must be a minimum of one week from a reference value. It is recognized that PSA fluctuations are such that the confirmatory PSA value might be less than the previous one. In these cases, that patient would still be eligible provided the next PSA was greater than the first rising PSA value. Patients must have PSA greater than or equal to 5.0.
At least one new lesion on bone scan.
Progressive measurable disease.

Patients must have undergone bilateral surgical castration or must continue on GNRH agonist.

Those patients receiving an anti-androgen agent and are entering the trial due to a rise in PSA must demonstrate a continued rise in PSA 4 weeks after stopping flutamide and 6 weeks after stopping bicalutamide or nilutamide.

Patients may not have received any chemotherapy for metastatic prostate cancer

Age greater than or equal to 18 years

Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

Life expectancy of greater than 3 months

Patients must have adequate organ and marrow function as defined below:

Leukocytes- greater than or equal to 3,000/microliter

Absolute neutrophil count- greater than or equal to 1,500/microliter

Platelets- greater than or equal to 100,000/microliter

Hemoglobin- greater than or equal to 8.0g/L - transfusions acceptable

Total bilirubin- less than or equal to 1.5 times the institutional upper limits of normal

Aspartate aminotransferase (AST)serum glutamic oxaloacetic transaminase(SGOT) and alanine aminotransferase (ALT)serum glutamic pyruvic transaminase(SGPT) - less than or equal to 2.5 times the institutional upper limits of normal

Creatinine or Creatinine clearance- less than or equal to 1.5 times the institutional upper limits of normal or greater than or equal to 40 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.

Recovered from any toxicity from surgery or radiotherapy

Must be willing to travel from their home to the National Institutes of Health (NIH) for follow-up visits

Able and willing to follow instructions and conform to protocol.

Patients may have had no other active malignancy within the past 2 years with the exception of non-melanoma skin cancer and superficial bladder carcinoma

No history of myocardial infarction within the past 6 months, uncontrolled congestive heart failure (CHF) or uncontrolled angina pectoris

Patients must agree to use adequate contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 2 months after completion.

Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA

Present clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) brain scan.

Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), unstabl

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Data sourced from ClinicalTrials.gov (NCT00089609). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.