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Docetaxel and Prednisone With or Without Bevacizumab in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

Primary Purpose

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

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
docetaxel
placebo
prednisone
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

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

Inclusion Criteria: Patients must have histologically documented adenocarcinoma of the prostate with progressive systemic (clinically metastatic disease documented on bone, CT or MRI scan) disease despite castrate levels of testosterone due to orchiectomy or LHRH agonist; castrate levels of testosterone must be maintained All eligible patients must have a Gleason sum based on biopsy or TURP at the time of registration At the time of enrollment, patients must have evidence of progressive metastatic disease, either: Measurable disease with any level of serum PSA OR Non-measurable disease with PSA ≥ 5 ng/ml; patients with PSA ≥ 5 ng/ml only and no other radiographic evidence of metastatic prostate cancer 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 or MRI scan 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 and is not consistent with prostate cancer, then its neoplastic nature must 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 not included in above, 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 (≥ 5 ng/mL) which has risen serially on at least two occasions after the discontinuation of antiandrogen therapy, each at least one week apart; if the confirmatory PSA (#3) value is less than screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression The reference PSA value (#1) must be measured at the time of the discontinuation of antiandrogen therapy; and at least 2 PSA measurements must be made following the end of antiandrogen therapy and prior to registration (For the purposes of the nomogram calculator, the last PSA value recorded prior to the initiation of treatment will be considered the baseline PSA) Progression despite standard androgen deprivation therapy (i.e., LHRH agonist and/or orchiectomy) All antiandrogens (e.g., flutamide, megestrol acetate [even if taken for hot flashes], bicalutamide and nilutamide) of any dose must be discontinued at least 4 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 agonist) should not be discontinued At least 4 weeks since any other hormonal therapy, including ketoconazole and aminoglutethimide; the only exception to this time frame is that 5α-reductase inhibitors (e.g., finasteride, dutasteride) may be discontinued any time prior to registration 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 (including palliative) and fully recovered ≥ 8 weeks since the last dose of Strontium-89 or Samarium Patients receiving a bisphosphonate must be on a stable dose and must have started the bisphosphonate ≥ 4 weeks prior to initiating protocol treatment. Patients do not have to be on a bisphosphonate to qualify for the study; patients may initiate bisphosphonate therapy after completion of Cycle 1, if clinically indicated Patients enrolled on CALGB 90202 who have documented disease progression and have received at least 4 weeks of open label zoledronic acid treatment, are eligible for this study. No known brain metastases (brain imaging (MRI/CT) is not required) No current congestive heart failure (New York Heart Association Class II, III or IV) Patients with history of hypertension must be well controlled (< 160/90) on a regimen of anti-hypertensive therapy Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an in-range INR (usually between 2 and 3) or be on a stable dose of LMW heparin; patients receiving anti-platelet agents are also eligible; in addition, patients who are on daily prophylactic aspirin or anticoagulation for atrial fibrillation are eligible No significant history of bleeding events or GI perforation Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within 6 months of registration are not eligible Patients with a history of GI perforation within 12 months of registration are not eligible. No recent (within 12 months) arterial thrombotic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina or angina requiring surgical or medical intervention in the past 12 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) or any other arterial thrombotic event are also ineligible No serious or non-healing wound, ulcer or bone fracture No peripheral neuropathy ≥ grade 2 Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible PC-Spes, Saw Palmetto, and St. John's Wort must be discontinued before registration; the discontinuation of other herbal medications and food supplements is strongly encouraged; patients may continue on daily vitamins and calcium supplements ECOG performance status: 0-2 ANC ≥ 1500/μL Platelet count ≥ 100,000/μL Creatinine ≤ 1.5 x upper limits of normal Bilirubin ≤ 1.5 x upper limits of normal For patients with Gilbert's Disease, ≤ 2.5 X ULN is allowed AST ≤ 1.5 x upper limits of normal PSA ≥ 5 ng/mL (if non-measurable disease) Urine protein to creatinine ratio < 1.0

Sites / Locations

  • Yale University
  • Cancer and Leukemia Group B

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I

Arm II

Arm Description

Patients receive docetaxel IV over 1 hour and placebo IV over 30-90 minutes on day 1. Patients also receive oral prednisone once daily on days 1-21.

Patients receive docetaxel and prednisone as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1.

Outcomes

Primary Outcome Measures

Overall Survival
Overall Survival (OS) was measured from the date of randomization to date of death due to any cause. OS was estimated using the Kaplan Meier method.

Secondary Outcome Measures

Proportion of Participants Who Experienced at Least a 50% Post-therapy PSA (Prostate-Specific Antigen) Decline
PSA decline will be reported on all patients and will be defined as a decrease in PSA value by >= 50% for two successive evaluations at least 4 weeks apart. The reference PSA value for these declines should be measured within 2 weeks before starting therapy.
Progression-free Survival (PFS)
PFS was defined as the data of randomization to date of progression or death due to any cause, whichever occurs first. PFS was estimated using the Kaplan Meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Proportion of Participants Who Experience (Maximum) Grade 3 or Higher Toxicities
The National Cancer Institute (NCI) Criteria for Adverse Events(CTCAE) Version 3.0 was used to evaluate toxicity. These events were considered at least possibly related to treatment. Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death

Full Information

First Posted
May 4, 2005
Last Updated
April 21, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00110214
Brief Title
Docetaxel and Prednisone With or Without Bevacizumab in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy
Official Title
A Randomized Double-Blinded Placebo Controlled Phase III Trial Comparing Doctaxel and Prednisone With and Without Bevacizumab (IND #7921, NSC #704865) in Men With Hormone Refractory Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
This randomized phase III trial is studying docetaxel, prednisone, and bevacizumab to see how well they work compared to docetaxel and prednisone in treating patients with prostate cancer that did not respond to hormone therapy. Drugs used in chemotherapy, such as docetaxel and prednisone, 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 bevacizumab, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether docetaxel, prednisone, and bevacizumab are more effective than docetaxel and prednisone in treating prostate cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To determine if the addition of bevacizumab to docetaxel and prednisone increases overall survival compared to docetaxel and prednisone alone in patients with HRPC. SECONDARY OBJECTIVES: I. To compare the progression-free survival of these two regimens in patients with HRPC. II. To compare the two regimens on the proportion of patients who experience a 50% post-therapy PSA decline from baseline. III. To compare the two regimens with respect to the proportion of patients who experience grade 3 or higher toxicities. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to predicted 24-month survival probability (< 10% vs 10-29.9% vs ≥ 30%), age (< 65 years vs ≥ 65 years), and prior history of arterial events (i.e., cardiac ischemia/infarction, CNS cerebrovascular ischemia, peripheral arterial ischemia, or CNS hemorrhage) (yes vs no). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive docetaxel IV over 1 hour and placebo IV over 30-90 minutes on day 1. Patients also receive oral prednisone once daily on days 1-21. ARM II: Patients receive docetaxel and prednisone as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. In both arms, courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 5 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 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1050 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive docetaxel IV over 1 hour and placebo IV over 30-90 minutes on day 1. Patients also receive oral prednisone once daily on days 1-21.
Arm Title
Arm II
Arm Type
Experimental
Arm Description
Patients receive docetaxel and prednisone as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1.
Intervention Type
Drug
Intervention Name(s)
docetaxel
Other Intervention Name(s)
RP 56976, Taxotere, TXT
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
prednisone
Other Intervention Name(s)
DeCortin, Deltra
Intervention Description
Given orally
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
Overall Survival
Description
Overall Survival (OS) was measured from the date of randomization to date of death due to any cause. OS was estimated using the Kaplan Meier method.
Time Frame
Duration of study (up to 5 years)
Secondary Outcome Measure Information:
Title
Proportion of Participants Who Experienced at Least a 50% Post-therapy PSA (Prostate-Specific Antigen) Decline
Description
PSA decline will be reported on all patients and will be defined as a decrease in PSA value by >= 50% for two successive evaluations at least 4 weeks apart. The reference PSA value for these declines should be measured within 2 weeks before starting therapy.
Time Frame
Duration of study (up to 5 years)
Title
Progression-free Survival (PFS)
Description
PFS was defined as the data of randomization to date of progression or death due to any cause, whichever occurs first. PFS was estimated using the Kaplan Meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame
Duration of study (up to 5 years)
Title
Proportion of Participants Who Experience (Maximum) Grade 3 or Higher Toxicities
Description
The National Cancer Institute (NCI) Criteria for Adverse Events(CTCAE) Version 3.0 was used to evaluate toxicity. These events were considered at least possibly related to treatment. Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death
Time Frame
During treatment (up to 2 years)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically documented adenocarcinoma of the prostate with progressive systemic (clinically metastatic disease documented on bone, CT or MRI scan) disease despite castrate levels of testosterone due to orchiectomy or LHRH agonist; castrate levels of testosterone must be maintained All eligible patients must have a Gleason sum based on biopsy or TURP at the time of registration At the time of enrollment, patients must have evidence of progressive metastatic disease, either: Measurable disease with any level of serum PSA OR Non-measurable disease with PSA ≥ 5 ng/ml; patients with PSA ≥ 5 ng/ml only and no other radiographic evidence of metastatic prostate cancer 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 or MRI scan 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 and is not consistent with prostate cancer, then its neoplastic nature must 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 not included in above, 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 (≥ 5 ng/mL) which has risen serially on at least two occasions after the discontinuation of antiandrogen therapy, each at least one week apart; if the confirmatory PSA (#3) value is less than screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression The reference PSA value (#1) must be measured at the time of the discontinuation of antiandrogen therapy; and at least 2 PSA measurements must be made following the end of antiandrogen therapy and prior to registration (For the purposes of the nomogram calculator, the last PSA value recorded prior to the initiation of treatment will be considered the baseline PSA) Progression despite standard androgen deprivation therapy (i.e., LHRH agonist and/or orchiectomy) All antiandrogens (e.g., flutamide, megestrol acetate [even if taken for hot flashes], bicalutamide and nilutamide) of any dose must be discontinued at least 4 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 agonist) should not be discontinued At least 4 weeks since any other hormonal therapy, including ketoconazole and aminoglutethimide; the only exception to this time frame is that 5α-reductase inhibitors (e.g., finasteride, dutasteride) may be discontinued any time prior to registration 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 (including palliative) and fully recovered ≥ 8 weeks since the last dose of Strontium-89 or Samarium Patients receiving a bisphosphonate must be on a stable dose and must have started the bisphosphonate ≥ 4 weeks prior to initiating protocol treatment. Patients do not have to be on a bisphosphonate to qualify for the study; patients may initiate bisphosphonate therapy after completion of Cycle 1, if clinically indicated Patients enrolled on CALGB 90202 who have documented disease progression and have received at least 4 weeks of open label zoledronic acid treatment, are eligible for this study. No known brain metastases (brain imaging (MRI/CT) is not required) No current congestive heart failure (New York Heart Association Class II, III or IV) Patients with history of hypertension must be well controlled (< 160/90) on a regimen of anti-hypertensive therapy Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an in-range INR (usually between 2 and 3) or be on a stable dose of LMW heparin; patients receiving anti-platelet agents are also eligible; in addition, patients who are on daily prophylactic aspirin or anticoagulation for atrial fibrillation are eligible No significant history of bleeding events or GI perforation Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within 6 months of registration are not eligible Patients with a history of GI perforation within 12 months of registration are not eligible. No recent (within 12 months) arterial thrombotic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina or angina requiring surgical or medical intervention in the past 12 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) or any other arterial thrombotic event are also ineligible No serious or non-healing wound, ulcer or bone fracture No peripheral neuropathy ≥ grade 2 Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible PC-Spes, Saw Palmetto, and St. John's Wort must be discontinued before registration; the discontinuation of other herbal medications and food supplements is strongly encouraged; patients may continue on daily vitamins and calcium supplements ECOG performance status: 0-2 ANC ≥ 1500/μL Platelet count ≥ 100,000/μL Creatinine ≤ 1.5 x upper limits of normal Bilirubin ≤ 1.5 x upper limits of normal For patients with Gilbert's Disease, ≤ 2.5 X ULN is allowed AST ≤ 1.5 x upper limits of normal PSA ≥ 5 ng/mL (if non-measurable disease) Urine protein to creatinine ratio < 1.0
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Kelly
Organizational Affiliation
Cancer and Leukemia Group B
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Cancer and Leukemia Group B
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60606
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34616010
Citation
Quintanilha JCF, Wang J, Sibley AB, Jiang C, Etheridge AS, Shen F, Jiang G, Mulkey F, Patel JN, Hertz DL, Dees EC, McLeod HL, Bertagnolli M, Rugo H, Kindler HL, Kelly WK, Ratain MJ, Kroetz DL, Owzar K, Schneider BP, Lin D, Innocenti F. Bevacizumab-induced hypertension and proteinuria: a genome-wide study of more than 1000 patients. Br J Cancer. 2022 Feb;126(2):265-274. doi: 10.1038/s41416-021-01557-w. Epub 2021 Oct 6. Erratum In: Br J Cancer. 2021 Dec 1;:
Results Reference
derived
PubMed Identifier
34028627
Citation
Quintanilha JCF, Liu Y, Etheridge AS, Yazdani A, Kindler HL, Kelly WK, Nixon AB, Innocenti F. Plasma levels of angiopoietin-2, VEGF-A, and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance). Angiogenesis. 2022 Feb;25(1):47-55. doi: 10.1007/s10456-021-09799-1. Epub 2021 May 24.
Results Reference
derived

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Docetaxel and Prednisone With or Without Bevacizumab in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

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