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A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00942578
First received: July 18, 2009
Last updated: August 23, 2014
Last verified: November 2013
  Purpose

Background:

  • Prednisone and docetaxel have been used successfully in treating patients with prostate cancer, either when used alone or in combination with other agents. Researchers believe that these anticancer effects can be increased by giving them in this specific combination.
  • A previous study at the National Cancer Institute combined docetaxel and prednisone with bevacizumab and thalidomide. The results of this study were promising; however, most patients in the study required a dose reduction of thalidomide because of its side effects.
  • Lenalidomide, a drug similar to thalidomide, may have less severe side effects. Based on previous studies, lenalidomide is well tolerated in patients with solid tumors when used alone or in combination with docetaxel, and it may be a good substitute for thalidomide.

Objectives:

  • To determine if lenalidomide is an appropriate and effective substitute for thalidomide in treating prostate cancer.
  • To evaluate the safety and effectiveness of bevacizumab, lenalidomide, docetaxel, and prednisone as a prostate cancer treatment, and to study any side effects.

Eligibility:

- Men 18 years of age and older who have been diagnosed with metastatic prostate cancer that has not responded to standard treatment, including surgical removal of the testicles or treatment with androgen (sex-hormone) suppressing drugs.

Design:

  • Participants will have a complete medical history and physical examination before beginning the study.
  • Patients will be treated with 21-day cycles with a combination of four drugs:
  • (1) Docetaxel, which will be given into a vein for 60 minutes on the first day of each 21-day cycle. Patients will take dexamethasone (a steroid agent) before and after taking docetaxel.
  • (2) Prednisone, which will be taken by mouth daily.
  • (3) Bevacizumab, which will be given through a vein over 30 to 90 minutes on the first day of each 21-day cycle following the infusion of docetaxel.
  • (4) Lenalidomide, which will be taken by mouth during the first 2 weeks of each 21-day cycle. The dose of lenalidomide may be adjusted if side effects develop.
  • Patients will also receive enoxaparin, a subcutaneous injection administered daily, to prevent blood clots and/or pegfilgrastim, a subcutaneous injection on day 2 of each cycle, to improve white blood cell counts, as directed by researchers.

Condition Intervention Phase
Metastatic Prostate Cancer
Drug: Bevacizumab
Drug: Lenalidomide
Drug: Docetaxel
Drug: Prednisone
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 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To assess safety of Lenalidomide at approved dosing schedule when combined with Docetaxel, Bevacizumab, and Prednisone in patients with mCRPC as measured by less than 25% Grade 4 toxicity and evaluation of the efficacy of the drug combination.

Secondary Outcome Measures:
  • Overall survival of the enrolled patients. Measurement of circulating prostate cancer cells and apoptotic endothelial cells before and after drug administration. Assessment of molecular markers of angiogenesis before and after drug administrati...

Enrollment: 63
Study Start Date: July 2009
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Bevacizumab
    N/A
    Drug: Lenalidomide
    N/A
    Drug: Docetaxel
    N/A
    Drug: Prednisone
    N/A
  Show Detailed Description

  Eligibility

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

Castrate-resistant metastatic adenocarcinoma of the prostate defined as progressive metastatic disease (see below) while on GnRH agonists or post surgical castration. All patients enrolled will be required to have evaluable disease on imaging studies.

Histopathological documentation of prostate cancer confirmed in the NCI Laboratory of Pathology at the National Institutes of Health, the Pathology Department at Walter Reed Medical Center, or the Pathology Department at National Naval Medical Center, prior to starting this study. In addition, patients whose slides are lost or unavailable will be eligible for the study if they provide documentation of prostate cancer and if they meet criteria of clinically progressive prostate cancer as outlined (see below).

Clinically progressive prostate cancer documented prior to entry. Progression must be evidenced and documented by any of the following parameters:

i) Two consecutively rising PSA levels apart of 2 weeks

ii) At least one new lesion on bone scans.

iii) Progressive measurable disease.

Patients must have undergone bilateral surgical castration or must continue on GnRH agonist.

Those patients receiving an anti-androgen agent for at least 6 months and are entering the trial due to a rise in PSA must demonstrate a continued rise in PSA 4 weeks after stopping flutamide and 6 weeks after stopping bicalutamide or nilutamide.

May not have received any chemotherapy or antiangiogenic therapy (including thalidomide, lenalidomide, bevacizumab and its target s receptor inhibitors) for metastatic prostate cancer. (Prior immunotherapy/vaccine, experimental hormonal therapy, radiation and (neo)adjuvant chemotherapy is permitted)

Age greater than or equal to 18 years

ECOG performance status less than or equal to 2

Must have adequate organ and marrow function as defined below:

Laboratory Test and Required Value:

  • Leukocytes greater than or equal to 3,000/microL
  • Absolute neutrophil count greater than or equal to 1,500/ microL
  • Platelets greater than or equal to 100,000/ microL
  • Total bilirubin less than or equal to 1.5 times the institutional upper limits of normal, or less than or equal to 3 mg/dl in a subject with Gilbert Syndrome
  • AST (SGOT) and ALT (SGPT) less than or equal to 2.5 times the institutional upper limit of normal
  • Creatinine less than or equal to 1.5 times the institutional upper limits of normal

OR

-Creatinine clearance greater than or equal to 50 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.

Recovered from any acute toxicity from surgery or radiotherapy, with minimum 4 weeks from major surgical procedures and 2 weeks from radiotherapy

Must be willing to travel from their home to the NIH for follow-up visits

Able and willing to follow instructions and conform to protocol.

Patients may have had no other active malignancy within the past 2 years with the exception of non-melanoma skin cancer and superficial bladder carcinoma.

No history of myocardial infarction within the past 6 months, uncontrolled CHF or uncontrolled angina pectoris

Patients must agree to use adequate contraception (abstinence; hormonal or barrier method of birth control) prior to the study, during the study, and at least six months after completion. Males must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least six months following, even if a man has undergone a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure as indicated in the consent.

Subjects must agree not to share study drug and not donate blood, sperm, or semen. A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

Present clinical signs or symptoms of current active brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan. Patients with previously treated brain metastases are allowed to participate in the study.

--Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (MRI or CT). (Stable dose of anticonvulsants are allowed). Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.

Uncontrolled, intercurrent illness including, but not limited to, symptomatic congestive heart failure (AHA Class II or worse), unstable angina pectoris

Psychiatric illness/social situations that would limit compliance with study requirements.

Prior history of hypertensive crisis or hypertensive encephalopathy

Proteinuria, as demonstrated by a 24 hour protein of greater than or equal to 2000 mg. Urine protein should be screened by urine analysis. If urine dipstick is greater than 1.0+, then a 24 hour urine collection for total protein will need to be obtained and the level should be less than 2000 mg for patient enrollment.

Serious, non-healing wound, active ulcer, or untreated bone fracture, including tumor-related pathological fracture

Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with docetaxel, bevacizumab, and/or the combination.

Greater than Grade 2 peripheral neuropathy at baseline

History of allergic reaction to docetaxel, prednisone, lenalidomide and/or bevacizumab or related products.

Patients who are unable to ingest oral medication.

Patients on treatment for VTE.

History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1

Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy

Anticipation of need for major surgical procedures during the course of the study

Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1

Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair, aortic dissection or recent peripheral arterial thrombosis) within 6 months prior to Day 1

Patients with clinically significant cardiovascular disease are excluded

  • Inadequately controlled HTN (SBP greater than 160 mmHg and/or DBP greater than 90 mmHg despite antihypertensive medication)
  • History of CVA within 6 months (see additional requirement for adjuvant protocols), myocardial infarction or unstable angina within 6 months (see additional requirement for adjuvant protocols)
  • New York heart association grade II or greater congestive heart failure
  • Serious and inadequately controlled cardiac arrhythmia
  • Clinically significant vascular disease as stated above

Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00942578

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: William L Dahut, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00942578     History of Changes
Other Study ID Numbers: 090195, 09-C-0195
Study First Received: July 18, 2009
Last Updated: August 23, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Dual Antiangiogenic Combination Therapy for mCRPC
Efficacy and Toxicity Profile
Single Stage Phase 2 With Early Stopping, Run In Phase For Toxicity
Correlative Measurements
Overall Survival Assessment
Metastatic Prostate Cancer
Prostate Cancer

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

ClinicalTrials.gov processed this record on August 26, 2014