A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT00942578|
Recruitment Status : Completed
First Posted : July 21, 2009
Results First Posted : October 11, 2018
Last Update Posted : October 11, 2018
- Prednisone and docetaxel have been used successfully in treating patients with prostate cancer, either when used alone or in combination with other agents. Researchers believe that these anticancer effects can be increased by giving them in this specific combination.
- A previous study at the National Cancer Institute combined docetaxel and prednisone with bevacizumab and thalidomide. The results of this study were promising; however, most patients in the study required a dose reduction of thalidomide because of its side effects.
- Lenalidomide, a drug similar to thalidomide, may have less severe side effects. Based on previous studies, lenalidomide is well tolerated in patients with solid tumors when used alone or in combination with docetaxel, and it may be a good substitute for thalidomide.
- To determine if lenalidomide is an appropriate and effective substitute for thalidomide in treating prostate cancer.
- To evaluate the safety and effectiveness of bevacizumab, lenalidomide, docetaxel, and prednisone as a prostate cancer treatment, and to study any side effects.
- Men 18 years of age and older who have been diagnosed with metastatic prostate cancer that has not responded to standard treatment, including surgical removal of the testicles or treatment with androgen (sex-hormone) suppressing drugs.
- Participants will have a complete medical history and physical examination before beginning the study.
- Patients will be treated with 21-day cycles with a combination of four drugs:
- (1) Docetaxel, which will be given into a vein for 60 minutes on the first day of each 21-day cycle. Patients will take dexamethasone (a steroid agent) before and after taking docetaxel.
- (2) Prednisone, which will be taken by mouth daily.
- (3) Bevacizumab, which will be given through a vein over 30 to 90 minutes on the first day of each 21-day cycle following the infusion of docetaxel.
- (4) Lenalidomide, which will be taken by mouth during the first 2 weeks of each 21-day cycle. The dose of lenalidomide may be adjusted if side effects develop.
- Patients will also receive enoxaparin, a subcutaneous injection administered daily, to prevent blood clots and/or pegfilgrastim, a subcutaneous injection on day 2 of each cycle, to improve white blood cell counts, as directed by researchers.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Prostate Cancer||Drug: Bevacizumab Drug: Lenalidomide Drug: Docetaxel Drug: Prednisone||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||63 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer|
|Actual Study Start Date :||July 16, 2009|
|Actual Primary Completion Date :||July 31, 2017|
|Actual Study Completion Date :||July 31, 2017|
Experimental: Single Arm - 4 Drug Combination
A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.
15 mg/kg cycle 1 day 1, repeated every 21 days
Other Name: Avastin
Once daily days 1-14 of every 21
Other Name: Revlimid
75 mg/m^2 intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)
Other Name: Taxotere
10 mg orally every day
Other Name: Deltasone
- Recommended Phase 2 Dose (RP2D) [ Time Frame: 3 weeks ]The RP2D is the dose at which there are no dose-limiting toxicities (defined as a ≥grade 3 hematological toxicity related to lenalidomide).
- Count of Participants With Dose-Limiting Toxicities (DLT) [ Time Frame: First 28 days of treatment. ]DLT is defined as a ≥grade 3 non-hematological toxicity related to lenalidomide.
- Median Time to Progression (TTP) [ Time Frame: median time of potential follow-up of 47.5 months ]TTP is evaluated from the on-study date until the date of progression or last follow-up after progression.
- Median Overall Survival of Patients Studied [ Time Frame: median time of potential follow-up of 47.5 months ]OS is evaluated from the on-study date until the date of death or last follow-up.
- Count of Participants With Changes in Circulating Apoptotic Endothelial Cells (CAEC) From Baseline After Drug Administration [ Time Frame: After drug administration, an average of 3 months ]The definition of an increase is any increase (any number greater than zero) in the percent CAEC among total peripheral blood mononuclear cells comparing each patient's percent CAEC among total peripheral blood mononuclear cells at baseline to each patient's percent CAEC among total peripheral blood mononuclear cells at cycle 3 day 1. The definition of a decrease is any decrease (any number less than zero) in the percent CAEC among total peripheral blood mononuclear cells comparing each patient's percent CAEC among total peripheral blood mononuclear cells at baseline to each patient's percent CAEC among total peripheral blood mononuclear cells at cycle 3 day 1.
- Changes in the Molecular Markers of Angiogenesis (i.e Serum VEGF) Before and After Administration of Docetaxel, Prednisone,Lenalidomide and Bevacizumab [ Time Frame: median time of potential follow-up of 47.5 months ]Serum and urine samples were collected before and after administration of Docetaxel, Prednisone, Lenalidomide and Bevacizumab to measure VEGF levels.
- Survival Based on Expression of Programmed Cell Death Protein 1 (PD-1) on Cluster of Differentiation 8 (CD8) + T Cells [ Time Frame: median time of potential follow-up of 47.5 months ]Expression of PD-1 on CD8 + T cells was evaluated by flow cytometry. High and low expression are based on the median values. Patients with a low expression of PD-1 proteins had better survival than those with a high expression.
- Survival Based on Expression of T Cell Immunoglobulin and Mucin Domain (TIM-3) on Cluster of Differentiation 8 (CD8) + T Cells [ Time Frame: 46.5 months ]Expression of TIM-3 on CD8 + T cells was evaluated by flow cytometry.
- Count of Participants With a Radiologic Response [ Time Frame: median time of potential follow-up of 47.5 months ]Radiologic response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 criteria. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
- Count of Participants With Prostatic Antigen-Specific (PSA) Declines [ Time Frame: median time of potential follow-up of 47.5 months ]PSA decline is defined as a ≥50% decline in measurable disease. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20 mm by chest x-ray, as ≥10 mm with computed tomography, or ≥10 mm with calipers by clinical exam.
- Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered the Four-Drug Combination [ Time Frame: Date treatment consent signed to date off study, approximately 93 months and 22 days. ]Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00942578
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Ravi A Madan, M.D.||National Cancer Institute (NCI)|