Study of Bevacizumab and Erlotinib for Patients With Hormone Refractory Prostate Cancer

This study has been terminated.
(Poor enrollment)
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov Identifier:
NCT00996502
First received: October 14, 2009
Last updated: February 20, 2013
Last verified: February 2013
  Purpose

The primary objectives of this study are to evaluate the safety and best dose of a regimen including bevacizumab and erlotinib in combination with docetaxel and prednisone. In addition, the investigators wish to evaluate how well these drugs might work against this disease. Bevacizumab and erlotinib are novel drugs that attack the blood vessels supplying the tumor cells and attack a receptor on the tumor cells, respectively. This study has two parts. In the first part of the study, eighteen patients will be enrolled. Patients will receive escalating doses of docetaxel in combination with standard doses of bevacizumab and erlotinib until the safest dose is determined. An additional 37 patients will enter into the second part of the study and all will receive the safest dose. In this part of the study, the effectiveness of this regimen against hormone refractory prostate cancer (HRPC) will be monitored by evaluating prostate-specific antigen (PSA) and objective response of the tumor.


Condition Intervention Phase
Prostate Cancer
Drug: Bevacizumab, Erlotinib, Docetaxel, Prednisone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Bevacizumab and Erlotinib in Combination With Docetaxel and Prednisone for Patients With Hormone Refractory Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Phase I: Maximum tolerated dose of docetaxel, erlotinib, bevacizumab, and prednisone [ Time Frame: After three 21-day cycles ] [ Designated as safety issue: Yes ]
  • Phase II: To determine the proportion of patients alive at one year [ Time Frame: One year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate at the recommended Phase II dose level of docetaxel, bevacizumab, erlotinib, and prednisone [ Time Frame: Every 9 weeks ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: July 2006
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab, Erlotinib, Docetaxel, Prednisone
Dose escalation of intravenous docetaxel on Day 1 of each cycle at each cohort level before bevacizumab infusion. The bevacizumab administration will be a continuous IV infusion at a constant dose every three weeks and erlotinib administered PO daily from days 2-16. All patients will receive prednisone 5mg PO bid.
Drug: Bevacizumab, Erlotinib, Docetaxel, Prednisone

Phase I:

  • Cohort 1: 55mg/m2 of Docetaxel on Day 1 of the cycle, 15mg/kg of Bevacizumab every 3 weeks, 200 mg of Erlotinib PO daily days 2-16, 5 mg of prednisone PO bid
  • Cohort 2: 65mg/m2 of Docetaxel on Day 1 of the cycle, 15mg/kg of Bevacizumab every 3 weeks, 200 mg of Erlotinib PO daily days 2-16, 5 mg of prednisone PO bid
  • Cohort 3: 75mg/m2 of Docetaxel on Day 1 of the cycle, 15mg/kg of Bevacizumab every 3 weeks, 200 mg of Erlotinib PO daily days 2-16, 5 mg of prednisone PO bid

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 allowed.
  • 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 biopsies).
  • 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 adjustment.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00996502

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Genentech, Inc.
Investigators
Principal Investigator: Daniel P Petrylak, MD Columbia University
  More Information

No publications provided

Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT00996502     History of Changes
Other Study ID Numbers: AAAB8399
Study First Received: October 14, 2009
Last Updated: February 20, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Bevacizumab
Docetaxel
Erlotinib
Prednisone
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Inflammatory Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Glucocorticoids
Growth Inhibitors
Growth Substances
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 29, 2014