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Combination Chemotherapy Plus Bevacizumab in Treating Patients With Metastatic Prostate Cancer

Primary Purpose

Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
estramustine phosphate sodium
docetaxel
bevacizumab
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinoma of the Prostate

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: Patients must have histologically documented adenocarcinoma of the prostate with progressive systemic (metastatic) disease despite castrate levels of testosterone due to orchiectomy or LHRH agonist (which must be continued); castrate levels of testosterone must be maintained At the time of enrollment, patients must have evidence of metastatic disease, either: Measurable disease (with any PSA) OR Non-measurable disease with PSA >= 5 ng/ml; patients with PSA >= 5 ng/ml only are not eligible DEFINITION OF MEASURABLE DISEASE/TARGET LESIONS Any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques: 1) physical exam for clinically palpable lymph nodes and superficial skin lesions, 2) chest X-ray for clearly defined lung lesions surrounded by aerated lung OR those lesions measured as >= 10 mm with a spiral CT scan or MRI Measurable lesions (up to a maximum of 10 in number) representative of all organs involved to be identified as target lesions; the sum of the longest diameters (LD) for all target lesions will be calculated and reported as baseline sum LD If measurable disease is confined to a solitary lesion then its neoplastic nature will need to be confirmed by histology Ultrasound may not be used to measure tumor lesions that are not easily accessible clinically DEFINITION OF NON-MEASURABLE DISEASE/NON-TARGET LESIONS Non-target lesions include all other lesions, including small lesions with longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan and truly non-measurable lesions, which include: Bone lesions Pleural or pericardial effusions, ascites CNS lesions, leptomeningeal disease Irradiated lesions, unless progression documented after RT Patients must have demonstrated evidence of progressive disease since the most recent change in therapy; progressive disease is defined as any one of the following (measurable disease, bone scan, or PSA progression): MEASURABLE DISEASE PROGRESSION: Objective evidence of increase > 20% in the sum of the longest diameters (LD) of target lesions from the time of maximal regression or the appearance of one or more new lesions BONE SCAN PROGRESSION: Appearance of one or more new lesions on bone scan attributable to prostate cancer along with a PSA >= 5 ng/ml will constitute progression PSA PROGRESSION: An elevated PSA (at least >= 5 ng/ml) which has risen serially from baseline on two occasions each at least one week apart. If the confirmatory PSA (#3) value is less (i.e., #3b) than screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression Failure despite standard androgen deprivation therapy Flutamide and megestrol acetate (any dose) must be discontinued at least 4 weeks prior to registration; bicalutamide and nilutamide must be discontinued at least 6 weeks prior to registration. If improvement following antiandrogen withdrawal is noted, progression must be established using the criteria above; primary testicular androgen suppression (e.g., with an LHRH analogue) should not be discontinued At least 4 weeks since any hormonal therapy, including ketoconazole, aminoglutethimide, systemic steroids (any dose), megestrol acetate (any dose) No prior cytotoxic chemotherapy, including estramustine or suramin No prior anti-angiogenesis agents, including thalidomide and bevacizumab >= 4 weeks since major surgery and fully recovered >= 4 weeks since any prior radiation and fully recovered >= 8 weeks since the last dose of strontium-89 or Samarium Patients receiving bisphosphonate therapy prior to initiating protocol treatment must have received bisphosphonates for at least 1 month and have progressive disease despite this therapy CTC (ECOG) performance status: 0-2 No myocardial infarction or significant change in anginal pattern within one year or current congestive heart failure (NYHA Class 2 or higher) No deep venous thrombosis or pulmonary embolus within one year. No need for full-dose oral or parenteral anticoagulation; daily prophylactic aspirin is allowed No clinically significant peripheral neuropathy Granulocytes >= 1500/ul Platelet count >= 100,000/ul Creatinine =< 1.5 x upper limit of normal Bilirubin =< 1.0 x upper limit of normal AST =< 1.5 x upper limits of normal Urinalysis =< 1 + protein on dipstick PSA >= 5 ng/ml (if non-measurable disease) Serum Testosterone =< 50 ng/ml for patients who have not had bilateral orchiectomy

Sites / Locations

  • Cancer and Leukemia Group B

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy, bevacizumab)

Arm Description

Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV over 1 hour followed by bevacizumab IV over 30-90 minutes on day 2. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Time to objective progression
The Kaplan-Meier method will be used to estimate the time to disease progression.
Response rates (PSA and objective)
Response rates will be analyzed using both objective (CR and PR) and serological parameters. The Kaplan-Meier method will be used to estimate the response (objective and PSA) duration.
Toxicity as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 2.0

Secondary Outcome Measures

Overall survival
The Kaplan-Meier method will be used to estimate the overall survival.
Duration of response
Duration of PSA response is the date from the first 50% decline (or 75% decline) in PSA to the date when the patient met the criteria for progressive disease.

Full Information

First Posted
May 6, 2001
Last Updated
June 4, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00016107
Brief Title
Combination Chemotherapy Plus Bevacizumab in Treating Patients With Metastatic Prostate Cancer
Official Title
A Phase II Study Of Estramustine, Docetaxel, And Bevacizumab (IND # 7921, NSC # 704865) In Men With Hormone Refractory Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
June 2001 (undefined)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Phase II trial to study the effectiveness of combination chemotherapy plus monoclonal antibody therapy in treating patients who have metastatic prostate cancer that has not responded to previous hormone therapy. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab may stop the growth of cancer cells by stopping blood flow to the tumor. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To determine time to objective progression, response rate (objective and PSA response) and duration of response in men with hormone refractory prostate cancer treated with estramustine, docetaxel and bevacizumab. II. To determine the toxicity of this regimen in men with hormone refractory prostate cancer. III. To study the relationship of baseline VEGF levels in urine and plasma and changes in these levels to response and duration of response to treatment with bevacizumab, docetaxel and estramustine. OUTLINE: Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV over 1 hour followed by bevacizumab IV over 30-90 minutes on day 2. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed at least every 3 months for 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemotherapy, bevacizumab)
Arm Type
Experimental
Arm Description
Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV over 1 hour followed by bevacizumab IV over 30-90 minutes on day 2. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
estramustine phosphate sodium
Other Intervention Name(s)
EM, Emcyt, Estracyt, Ro 22-2296/000
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
docetaxel
Other Intervention Name(s)
RP 56976, Taxotere, TXT
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Time to objective progression
Description
The Kaplan-Meier method will be used to estimate the time to disease progression.
Time Frame
From the initiation of treatment to the date of progressive disease, assessed up to 2 years
Title
Response rates (PSA and objective)
Description
Response rates will be analyzed using both objective (CR and PR) and serological parameters. The Kaplan-Meier method will be used to estimate the response (objective and PSA) duration.
Time Frame
Up to 2 years
Title
Toxicity as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 2.0
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
The Kaplan-Meier method will be used to estimate the overall survival.
Time Frame
Up to 2 years
Title
Duration of response
Description
Duration of PSA response is the date from the first 50% decline (or 75% decline) in PSA to the date when the patient met the criteria for progressive disease.
Time Frame
From the date of the first CR or PR to the date that the patient had progressive disease, assessed up to 2 years

10. Eligibility

Sex
Male
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically documented adenocarcinoma of the prostate with progressive systemic (metastatic) disease despite castrate levels of testosterone due to orchiectomy or LHRH agonist (which must be continued); castrate levels of testosterone must be maintained At the time of enrollment, patients must have evidence of metastatic disease, either: Measurable disease (with any PSA) OR Non-measurable disease with PSA >= 5 ng/ml; patients with PSA >= 5 ng/ml only are not eligible DEFINITION OF MEASURABLE DISEASE/TARGET LESIONS Any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques: 1) physical exam for clinically palpable lymph nodes and superficial skin lesions, 2) chest X-ray for clearly defined lung lesions surrounded by aerated lung OR those lesions measured as >= 10 mm with a spiral CT scan or MRI Measurable lesions (up to a maximum of 10 in number) representative of all organs involved to be identified as target lesions; the sum of the longest diameters (LD) for all target lesions will be calculated and reported as baseline sum LD If measurable disease is confined to a solitary lesion then its neoplastic nature will need to be confirmed by histology Ultrasound may not be used to measure tumor lesions that are not easily accessible clinically DEFINITION OF NON-MEASURABLE DISEASE/NON-TARGET LESIONS Non-target lesions include all other lesions, including small lesions with longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan and truly non-measurable lesions, which include: Bone lesions Pleural or pericardial effusions, ascites CNS lesions, leptomeningeal disease Irradiated lesions, unless progression documented after RT Patients must have demonstrated evidence of progressive disease since the most recent change in therapy; progressive disease is defined as any one of the following (measurable disease, bone scan, or PSA progression): MEASURABLE DISEASE PROGRESSION: Objective evidence of increase > 20% in the sum of the longest diameters (LD) of target lesions from the time of maximal regression or the appearance of one or more new lesions BONE SCAN PROGRESSION: Appearance of one or more new lesions on bone scan attributable to prostate cancer along with a PSA >= 5 ng/ml will constitute progression PSA PROGRESSION: An elevated PSA (at least >= 5 ng/ml) which has risen serially from baseline on two occasions each at least one week apart. If the confirmatory PSA (#3) value is less (i.e., #3b) than screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression Failure despite standard androgen deprivation therapy Flutamide and megestrol acetate (any dose) must be discontinued at least 4 weeks prior to registration; bicalutamide and nilutamide must be discontinued at least 6 weeks prior to registration. If improvement following antiandrogen withdrawal is noted, progression must be established using the criteria above; primary testicular androgen suppression (e.g., with an LHRH analogue) should not be discontinued At least 4 weeks since any hormonal therapy, including ketoconazole, aminoglutethimide, systemic steroids (any dose), megestrol acetate (any dose) No prior cytotoxic chemotherapy, including estramustine or suramin No prior anti-angiogenesis agents, including thalidomide and bevacizumab >= 4 weeks since major surgery and fully recovered >= 4 weeks since any prior radiation and fully recovered >= 8 weeks since the last dose of strontium-89 or Samarium Patients receiving bisphosphonate therapy prior to initiating protocol treatment must have received bisphosphonates for at least 1 month and have progressive disease despite this therapy CTC (ECOG) performance status: 0-2 No myocardial infarction or significant change in anginal pattern within one year or current congestive heart failure (NYHA Class 2 or higher) No deep venous thrombosis or pulmonary embolus within one year. No need for full-dose oral or parenteral anticoagulation; daily prophylactic aspirin is allowed No clinically significant peripheral neuropathy Granulocytes >= 1500/ul Platelet count >= 100,000/ul Creatinine =< 1.5 x upper limit of normal Bilirubin =< 1.0 x upper limit of normal AST =< 1.5 x upper limits of normal Urinalysis =< 1 + protein on dipstick PSA >= 5 ng/ml (if non-measurable disease) Serum Testosterone =< 50 ng/ml for patients who have not had bilateral orchiectomy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joel Picus
Organizational Affiliation
Cancer and Leukemia Group B
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer and Leukemia Group B
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60606
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Combination Chemotherapy Plus Bevacizumab in Treating Patients With Metastatic Prostate Cancer

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