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A Phase I/II Study of Bevacizumab and Erlotinib in Combination With Docetaxel and Prednisone for Patients With Hormone Refractory Prostate Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Prostate Cancer

Thank you

Trial Information

A Phase I/II Study of Bevacizumab and Erlotinib in Combination With Docetaxel and Prednisone for Patients With Hormone Refractory Prostate Cancer

In this Phase I/Phase II study, the primary objectives are to establish the maximum
tolerated dose of docetaxel, erlotinib, bevacizumab, and prednisone in patients with
metastatic hormone refractory prostate cancer and to determine the efficacy of this regimen
for treatment of metastatic HRPC. In the phase I portion of the study, eligible patients
will be enrolled and treated using a "3+3" design. Docetaxel will be started at 55 mg/m2
every cycle (21 days) and dose escalated by 10 mg/m2 at each cohort level. The dose of
bevacizumab will be held constant at 15 mg/kg every 3 weeks and erlotinib will be provided
at 200 mg PO daily from days 216 as described in previous safety studies. All patients will
receive prednisone 5 mg PO bid. Eighteen patients will be treated in the phase I portion.
The phase II dose for this combined treatment will be defined as either the highest dosage
cohort in which 6 patients are treated and there are less than 3 DLTs; or the combination of
docetaxel, erlotinib, and bevacizumab at the cohort 3 dose level, whichever is the lower
dose. Another 37 patients will be enrolled for the phase II study. All patients will receive
the phase II recommended dose as determined by the phase I portion of the study.

Inclusion Criteria:

- Patients must have a histologically documented diagnosis of prostate adenocarcinoma
(PCa) not amenable to curative therapy.

- At the time of enrollment, patients must have evidence of progressive metastatic
disease defined as any one of the following:

- Progression of measurable disease with any level of serum PSA Measurable
disease/target lesions will be defined as any lesion that can be measured as >20
mm in at least one dimension with physical exam (for superficial skin lesions
and clinically palpable lymph nodes) or Chest X-ray for clearly defined lung
lesions. Measurable disease is also defined as lesions measured as >10 mm on CT
or MRI scan. Nonmeasurable disease/nontarget lesions are defined as lesions
that do not meet the criteria for measurable disease as described above and also
include bone lesions, pleural or pericardial effusions, ascites, CNS lesions,
and irradiated lesions (unless progression is documented after radiation
therapy). Measurable disease progression is defined as at least a 20% increase
in the sum of the longest diameters (LD) of target lesions since treatment
initiation or the appearance of one or more new lesions.

- Bone scan progression with PSA > 5 ng/ml Bone scans will be used to assess bone
lesions. Progression by bone scan criteria alone will require one or more new
lesions on bone scan that is attributable to prostate cancer. Intensity changes
on the bone scan will not be used to determine progression as increased uptake
does not correlate with progression of disease.

- PSA progression defined as: an initial elevated PSA (> 5 ng/ml) (PSA #1) that
has risen from baseline on two occasions at least one week apart (PSA #s 2 and
3). If the confirmatory PSA (PSA #3 ) is less than PSA #2, then an additional
PSA test will be required (PSA #4). The overall increase in the absolute-value
PSA level must be by at least 5 ng/ml and this increase must be confirmed by a
measurement at least one week later.

- Patients must have been surgically or medically castrated. Patients must continue on
medical castration (LHRH agonists) throughout protocol participation. Patients who
have discontinued LHRH agonists should be restarted on therapy. Testosterone levels
should be obtained prior to protocol initiation and should be less than 50 ng/mL.

- Previous antiandrogen and hormonal therapies must have been discontinued prior to
protocol initiation.

- Flutamide and megestrol acetate must be discontinued at least 4 weeks prior to
treatment initiation.

- Bicalutamide and nilutamide must be discontinued at least 6 weeks prior to
treatment initiation.

- Any other hormonal therapy including ketoconazole and systemic steroids must be
discontinued at least 4 weeks prior to treatment initiation.

- Herbal medications and food supplements must be discontinued before initiation
of protocol medications. Daily multivitamins and calcium supplementation are

- Patients receiving bisphosphonate therapies should have had this therapy started at
least 4 weeks prior to treatment initiation and should be on a stable dose. Although
being on bisphosphonate therapy is not an exclusion to the study, bisphosphonate
therapy should not be started during the study.

- Patients must be fully recovered and greater than 4 weeks from any major surgery or
radiation therapy. There must be greater than 8 weeks from last dose of
radionucleotide administration. There must be greater than 7 days from minor
surgical procedures (eg portacath insertion, fine needle aspirations or core

- Patients must have not had any previous cytotoxic therapy including estramustine or
suramin. Patients must not have had any previous therapies with anti-angiogenic
agents including thalidomide or bevacizumab.

- Patients may not have a history of brain metastases.

- Patients may not have current congestive heart failure (defined as New York Heart
Association Class II, III, or IV).

- Patients must have a well-controlled blood pressure. Those with a history of
hypertension should be well-controlled on a regimen of anti-hypertensive medication
(exclude if BP>150/100).

- Patients must not have a history of significant bleeding (e.g. upper or lower
gastrointestinal bleeding or hemoptysis) within 6 months of protocol enrollment.

- Patients must not have a history of gastrointestinal perforation, intraabdominal
fistula, or intraabdominal abscess within 6 months of protocol enrollment.

- Patients must not have had a history of arterial thrombotic events within 6 months of
protocol enrollment. These events include transient ischemic attacks,
cerebrovascular accidents, unstable angina and angina requiring medical or surgical
intervention, or myocardial infarction. Patients with severe and clinically
significant peripheral vascular disease (inability to walk more than one block
without claudication) are ineligible.

- Patients must not have any active serious non-healing wound, ulcer, or bone fracture.

- Patients must have an ECOG performance status between 0 and 1.

- Patients must be > 18 years old.

- Patients must have adequate hematopoietic and organ function:

- Adequate hematopoietic function: Absolute neutrophil count >/= 1500, hemoglobin
>/=9 g/dl, platelet count >/=100,000

- Adequate renal function: Creatinine <=1.5 x the upper limit of normal, urine
protein to creatinine ratio of <1.0 at screening (see Appendix A)

- Adequate liver function: Bilirubin <=1.5 x the upper limit of normal, AST or
ALT<= 2.5 X the upper limit of normal

- Patients must be able to swallow capsules.

- Patients must be willing to use effective means of contraception for study duration
and for at least 3 months after the completion of protocol therapy.

- Patients must be able to provide informed consent.

Exclusion Criteria:

- Patients with an active second malignancy other than basal or squamous skin cancer.
Patients who have completed all necessary therapy and are considered to have less
than a 30% risk of relapse by their physician are not thought to have an active
second malignancy.

- Patients who, in the opinion of the physician, have a serious concurrent uncontrolled
medical disorder.

- Patients with a disease for whom corticosteroids are contraindicated such as an
active peptic ulcer or uncontrolled diabetes. Patients with controlled diabetes may
be considered but must be made aware that their diabetic medications may require

- Patients who have received prior treatment with a tyrosine kinase inhibitor, EGFR
inhibitor, or VEGF inhibitor. For the phase II trial, patients who have had previous
cytotoxic therapy will not be eligible.

- Patients who are currently or have recently participated in a clinical trial (within
4 weeks from the first day of treatment) or are receiving investigational therapies.

- Patients who are unable to comply with study or follow-up procedures.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase I: Maximum tolerated dose of docetaxel, erlotinib, bevacizumab, and prednisone

Outcome Time Frame:

After three 21-day cycles

Safety Issue:


Principal Investigator

Daniel P Petrylak, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Columbia University


United States: Institutional Review Board

Study ID:




Start Date:

July 2006

Completion Date:

September 2015

Related Keywords:

  • Prostate Cancer
  • Prostatic Neoplasms



Columbia University Medical CenterNew York, New York  10032