Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) for Recurrent Glioblastoma Multiforme (GBM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01067469
First received: February 10, 2010
Last updated: September 18, 2014
Last verified: September 2014
  Purpose

The goal of this clinical research study is to learn if the combination of bevacizumab and lomustine can help to control glioblastoma. The safety of this combination will also be studied.


Condition Intervention Phase
Brain Cancer
Glioblastoma
Drug: Standard Dose Bevacizumab
Drug: Low Dose Bevacizumab
Drug: Lomustine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) In Adults With Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: Baseline to 6 months minimally, progression documented after 6 week treatment cycle ] [ Designated as safety issue: No ]
    Number of participants with no disease progression as measured by magnetic resonance imaging (MRI) scans. Participants followed by MRI scans, as used for baseline tumor measurements, and removed from study if progression is documented after any cycle of treatment. PFS determined from date of registration in the trial and not date of randomization into chemotherapy arms (i.e. after surgery for resection of recurrent tumor).


Estimated Enrollment: 102
Study Start Date: February 2010
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Standard Dose Bevacizumab
Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.
Drug: Standard Dose Bevacizumab
10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Experimental: Low Dose Bevacizumab + Lomustine
Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 75 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle.
Drug: Low Dose Bevacizumab
5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Lomustine
Starting dose of 75 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle.
Other Names:
  • CeeNU
  • CCNU

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Signed Informed Consent Form
  2. Age >/= 18 years
  3. Histologically confirmed glioblastoma in first, second or third relapse. A pathology report constitutes adequate documentation of histology for study inclusion. Subjects with an initial diagnosis of a lower grade glioma are eligible if a subsequent biopsy is determined to be glioblastoma. The amount of prior systemic therapy for this population is, nevertheless, restricted to three regimens, with one including temozolomide.
  4. Radiographic demonstration of disease progression following prior therapy
  5. Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on MRI performed within 14 days prior to registration (Day 1). Baseline MRIs for subjects who underwent salvage surgery after first or second relapse must be obtained >/= 4 weeks after the procedure. If receiving corticosteroids, subjects must be on a stable or decreasing dose of corticosteroids for >/= 5 days prior to baseline MRI.
  6. Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: 1) They have recovered from the effects of surgery. 2) Evaluable or measurable disease following resection of recurrent tumor is not mandated for eligibility into the study. 3) To best assess the extent of residual measurable disease post-operatively, a MRI should be done no later than 96 hours in the immediate post-operative period or 4-6 weeks post-operatively. .
  7. An interval of >/= 4 weeks since surgical resection is required prior to starting protocol therapy.
  8. Prior standard radiation for glioblastoma
  9. Prior chemotherapy: All first-relapse subjects must have received temozolomide. All second- and third-relapse subjects must have received temozolomide. Patients may not have received prior nitrosoureas.
  10. Recovery from the effects of prior therapy, including the following: Four weeks from cytotoxic agents (3 weeks from procarbazine, 2 weeks from vincristine); Four weeks from any investigational agent; One week from non-cytotoxic agents(eg accutane, thalidomide); Eight weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field; Patients may have had gliadel wafers during their original surgery but they must be >/= 9 months post their original surgery date.
  11. Prior therapy with gamma knife or other focal high-dose radiation is allowed, but the subject must have subsequent histologic documentation of recurrence or PET or MR Spectroscopic documentation of tumor, unless the recurrence is a new lesion outside the irradiated field
  12. Patients must have adequate bone marrow function (WBC >/= 3,000/µl, ANC >/= 1,500/mm^3, platelet count of >/= 100,000/mm^3, and hemoglobin >/= 10 gm/dl), adequate liver function (SGPT < 3 times normal and alkaline phosphatase < 2 times normal, bilirubin <1.5 mg/dl), adequate renal function (creatinine </= 1.5 mg/dL or creatinine clearance >/= 60 cc/min/1.73 m^2) and a urine protein:creatinine ratio of </=1 before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
  13. Patients must have a Karnofsky performance status (KPS) equal or greater than 60
  14. Use of an effective means of contraception in males and in females of childbearing potential. Women of childbearing potential must have a negative β-HCG pregnancy test documented within 14 days prior to registration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  15. Ability to comply with study and follow-up procedures
  16. Patients receiving treatment with other antiepileptic medications will not be excluded. Patients should preferably be treated with non-enzyme inducing anti-epileptic medications to avoid any potential interactions with lomustine. However, the use of non-enzyme inducing anti-epileptic medications is not mandatory. If enzyme-inducing antiepileptic drugs are used, monitoring of drug levels should be considered, as considered clinically appropriate by the treating physician.
  17. Patients on the following medications will be included: Anticoagulants/Anti-platelets: Patients on stable dose anticoagulants (e.g. warfarin, low molecular-weight heparin) and in-range INR (2-3) are eligible. Patients are allowed to take aspirin, clopidogrel, ticlopidine, Aggrenox, ibuprofen and other NSAIDS.
  18. Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while enrolled in the study.
  19. This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No exclusion to this study will be based on race. Minorities will actively be recruited to participate.

Exclusion Criteria:

  1. Prior treatment with anti-angiogenesis (eg bevacizumab, sorafenib, sunitinib) agent or nitrosurea (eg. lomustine, carmustine, nimustine).
  2. Prior treatment with polifeprosan 20 with carmustine wafer except for the patients with gliadel wafers >/= 9 months post their original surgery date.
  3. Patients must not have received any investigational agents within 28 days prior to commencing study treatment.
  4. Prior intracerebral agents
  5. Need for urgent palliative intervention for primary disease (e.g., impending herniation)
  6. Evidence of recent hemorrhage on baseline MRI of the brain with the following exceptions: (1) Presence of hemosiderin (2) Resolving hemorrhagic changes related to surgery (3) Presence of punctate hemorrhage in the tumor
  7. Blood pressure of > 140 mmHg systolic and > 90 mmHg diastolic
  8. History of hypertensive encephalopathy
  9. New York Heart Association (NYHA) Grade II or greater chronic heart failure(CHF)
  10. History of myocardial infarction or unstable angina within 6 months prior to Day 1
  11. History of stroke or transient ischemic attack within 6 months prior to study enrollment
  12. Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1
  13. Evidence of bleeding diathesis or coagulopathy or INR >1.5 unless on a stable dose of anticoagulation therapy. History of significant bleeding disorder unrelated to cancer, including: (1) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) (2) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) (3) Ongoing or recent (</= 3 months) significant gastrointestinal bleeding
  14. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
  15. History of intracerebral abscess within 6 months prior to Day 1
  16. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study
  17. Minor surgical procedures (excluding placement of a vascular access device), stereotactic biopsy, fine needle aspirations, or core biopsies within 7 days prior to Day 1
  18. Serious non-healing wound, ulcer, or bone fracture
  19. Pregnancy (positive pregnancy test) or lactation
  20. Known hypersensitivity to any component of bevacizumab
  21. History of any other malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible
  22. Pregnant or nursing females
  23. Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmia requiring medication
  24. Subjects unable to undergo an MRI with contrast
  25. Patients with a known allergy to bevacizumab, or a known allergy to nitrosoureas (eg. lomustine, carmustine, nimustine) will be excluded
  26. Patient must be able to tolerate the procedures required in this study including periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study. Inability to comply with protocol or study procedures (for example, an inability to swallow tablets) will be an exclusion criteria.
  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: NCT01067469

Contacts
Contact: John DeGroot, MD 713-792-2883

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: John DeGroot, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: John DeGroot, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01067469     History of Changes
Other Study ID Numbers: 2009-0597, NCI-2011-00559
Study First Received: February 10, 2010
Last Updated: September 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
CNS
Central Nervous System
malignant brain tumor
Recurrent Glioblastoma Multiforme
GBM
Bevacizumab
Lomustine
CCNU

Additional relevant MeSH terms:
Brain Neoplasms
Glioblastoma
Astrocytoma
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Nervous System Neoplasms
Neuroectodermal Tumors
Antibodies
Antibodies, Monoclonal
Bevacizumab
Lomustine
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Growth Inhibitors
Growth Substances
Immunologic Factors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 29, 2014