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

This study has been terminated.
(Poor enrollment; PI left the institution)
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov Identifier:
NCT00996502
First received: October 14, 2009
Last updated: March 23, 2016
Last verified: March 2016
  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: Docetaxel
Drug: Bevacizumab
Drug: Erlotinib
Drug: Prednisone
Phase 1
Phase 2

Study Type: Interventional
Study Design: 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:
  • Maximum Tolerated Dose of Docetaxel in Combination With Erlotinib, Bevacizumab, and Prednisone (Phase I) [ Time Frame: After three 21-day cycles ] [ Designated as safety issue: Yes ]

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 Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Proportion of Patients Alive at One Year (Phase II) [ Time Frame: One year ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: July 2006
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination regimen

Bevacizumab, Erlotinib, Docetaxel, Prednisone (dose escalation)

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
Drug: Docetaxel

Phase I:

  • Cohort 1: 55mg/m2 of Docetaxel on Day 1 of the cycle
  • Cohort 2: 65mg/m2 of Docetaxel on Day 1 of the cycle
  • Cohort 3: 75mg/m2 of Docetaxel on Day 1 of the cycle
Other Name: Taxotere
Drug: Bevacizumab
15mg/kg of Bevacizumab every 3 weeks
Other Name: Avastin
Drug: Erlotinib
200 mg of Erlotinib PO daily days 2-16
Other Name: Tarceva
Drug: Prednisone
5 mg of Prednisone PO bid
Other Name: Prednicot

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   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically documented diagnosis of prostate adenocarcinoma (PCa) not amenable to curative therapy.
  • Evidence of progressive metastatic disease.
  • 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.
  • 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.
  • 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).
  • No previous cytotoxic therapy including estramustine or suramin. No previous therapies with anti-angiogenic agents including thalidomide or bevacizumab.
  • No history of brain metastases.
  • No current congestive heart failure (defined as New York Heart Association Class II, III, or IV).
  • 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).
  • No history of significant bleeding (e.g. upper or lower gastrointestinal bleeding or hemoptysis) within 6 months of protocol enrollment.
  • No history of gastrointestinal perforation, intraabdominal fistula, or intraabdominal abscess within 6 months of protocol enrollment.
  • No history of arterial thrombotic events within 6 months of protocol enrollment. --No active serious non-healing wound, ulcer, or bone fracture.
  • ECOG performance status between 0 and 1.
  • > 18 years old.
  • Adequate hematopoietic and organ function.
  • Able to swallow capsules.
  • Willing to use effective means of contraception for study duration and for at least 3 months after the completion of protocol therapy.
  • Able to provide informed consent.

Exclusion Criteria:

  • 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.
  • Serious concurrent uncontrolled medical disorder.
  • 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.
  • 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.
  • Currently or have recently participated in a clinical trial (within 4 weeks from the first day of treatment) or are receiving investigational therapies.
  • 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

Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT00996502     History of Changes
Other Study ID Numbers: AAAB8399 
Study First Received: October 14, 2009
Results First Received: March 23, 2016
Last Updated: March 23, 2016
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on August 30, 2016