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

NCT01067469 | Completed Phase 2 Results DMC

• 2 other identifiers: 2009-0597NCI-2011-00559
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain Cancer; Glioblastoma

Keywords

CNS; Central Nervous System; malignant brain tumor; Recurrent Glioblastoma Multiforme; GBM; Bevacizumab; Lomustine; CCNU

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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).

  Documented from the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

Secondary Outcomes (5)

• Radiographic Response (RR)

  One year

• 6-month Progression-free Survival (PFS-6)

  6 Months

• Overall Survival (OS)

  through study completion, an average of 2 years

• Time to Progression (TTP)

  Up to One year

• Summary of Treatment Related Toxicities

  One year

Study Arms (2)

Standard Dose Bevacizumab

EXPERIMENTAL

Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.

Drug: Standard Dose Bevacizumab

Low Dose Bevacizumab + Lomustine

EXPERIMENTAL

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; Drug: Lomustine

Interventions

Standard Dose Bevacizumab DRUG

10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.

Also known as: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Standard Dose Bevacizumab

Low Dose Bevacizumab DRUG

5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle.

Also known as: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Low Dose Bevacizumab + Lomustine

Lomustine DRUG

Starting dose of 75 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle.

Also known as: CeeNU, CCNU

Low Dose Bevacizumab + Lomustine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form
• Age \>/= 18 years
• Radiographic demonstration of disease progression following prior therapy
• 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.
• 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. .
• An interval of \>/= 4 weeks since surgical resection is required prior to starting protocol therapy.
• Prior standard radiation for glioblastoma
• 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.
• 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.
• Prior therapy with gamma knife or other focal high-dose radiation is allowed, but the subject must have subsequent histologic documentation of recurrence or positron emission tomography (PET) or MR Spectroscopic documentation of tumor, unless the recurrence is a new lesion outside the irradiated field
• Patients must have adequate bone marrow function (WBC \>/= 3,000/µl, absolute neutrophil count (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.
• Patients must have a Karnofsky performance status (KPS) equal or greater than 60
• Use of an effective means of contraception in males and in females of childbearing potential. Women of childbearing potential must have a negative β-human chorionic gonadotropin (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.
• Ability to comply with study and follow-up procedures
• 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.

You may not qualify if:

• Prior treatment with anti-angiogenesis (eg bevacizumab, sorafenib, sunitinib) agent or nitrosurea (eg. lomustine, carmustine, nimustine).
• Prior treatment with polifeprosan 20 with carmustine wafer except for the patients with gliadel wafers \>/= 9 months post their original surgery date.
• Patients must not have received any investigational agents within 28 days prior to commencing study treatment.
• Prior intracerebral agents
• Need for urgent palliative intervention for primary disease (e.g., impending herniation)
• 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
• Blood pressure of \> 140 mmHg systolic and \> 90 mmHg diastolic
• History of hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater chronic heart failure(CHF)
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack within 6 months prior to study enrollment
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1
• 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
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
• History of intracerebral abscess within 6 months prior to Day 1

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Brain Neoplasms; Glioblastoma

Interventions

Bevacizumab; Lomustine

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Results Point of Contact

• Title: Dr. John F de Groot/Chair Ad Interim, Neuro-Oncology
• Organization: UT MD Anderson Cancer Center

jdegroot@mdanderson.org

713- 745-3072

Study Officials

• John DeGroot, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2010
• First Posted: February 11, 2010
• Study Start: January 1, 2010
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: March 17, 2020
• Results First Posted: March 17, 2020

Record last verified: 2020-03

Locations

US (1)