A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 63
- Locations
- 1
- Primary Endpoint
- Count of Participants With Dose-Limiting Toxicities (DLT)
Study Overview
Brief Summary
Background:
- 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.
Objectives:
- 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.
Eligibility:
- 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.
Design:
- 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.
Detailed Description
Background:
The dual antiangiogenic therapy with bevacizumab and thalidomide in combination with docetaxel and prednisone (ATTP) is highly active in patients with metastatic castration resistant prostate cancer (mCRPC), associated with unprecedented results (90% patients had PSA declines of greater than or equal to 50% and 64% ORR in measurable disease).
Most patients in the ATTP trial required dose reduction due to thalidomide toxicities.
Lenalidomide, an analogue of thalidomide, possesses both antiangiogenesis and inhibition of TNF-alpha, but has a favorable toxicity profile. Lenalidomide is well tolerated in patients with solid tumors when used alone or in combination with docetaxel.
To preserve the efficacy of ATTP and to potentially reduce toxicity, lenalidomide may be a good substitute for thalidomide.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 100 Years (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Bevacizumab (Drug)
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.
Intervention: Lenalidomide (Drug)
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.
Intervention: Docetaxel (Drug)
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.
Intervention: Prednisone (Drug)
Outcomes
Primary Outcomes
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.
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).
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.
Secondary Outcomes
- Survival Based on Expression of T Cell Immunoglobulin and Mucin Domain (TIM-3) on Cluster of Differentiation 8 (CD8) + T Cells(46.5 months)
- Survival Based on Expression of Programmed Cell Death Protein 1 (PD-1) on Cluster of Differentiation 8 (CD8) + T Cells(median time of potential follow-up of 47.5 months)
- Count of Participants With a Radiologic Response(median time of potential follow-up of 47.5 months)
- Count of Participants With Prostatic Antigen-Specific (PSA) Declines(median time of potential follow-up of 47.5 months)
- 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(Date treatment consent signed to date off study, approximately 93 months and 22 days.)
- Median Overall Survival of Patients Studied(median time of potential follow-up of 47.5 months)
- Changes in the Molecular Markers of Angiogenesis (i.e Serum VEGF) Before and After Administration of Docetaxel, Prednisone,Lenalidomide and Bevacizumab(median time of potential follow-up of 47.5 months)
- Count of Participants With Changes in Circulating Apoptotic Endothelial Cells (CAEC) From Baseline After Drug Administration(After drug administration, an average of 3 months)
Investigators
Ravi A. Madan, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)