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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

Phase 3
18 Years
Not Enrolling
Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer

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Trial Information

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


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.


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.

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

- 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

- 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

- (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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Overall Survival

Outcome 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.

Outcome Time Frame:

Duration of study (up to 5 years)

Safety Issue:


Principal Investigator

William Kelly

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B


United States: Food and Drug Administration

Study ID:




Start Date:

April 2005

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



Yale University New Haven, Connecticut  06520
Cancer and Leukemia Group B Chicago, Illinois  60606