NovoTTF-100A With Bevacizumab (Avastin) in Patients With Recurrent Glioblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Case Comprehensive Cancer Center
Sponsor:
Collaborators:
NovoCure Ltd.
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01894061
First received: July 3, 2013
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

NovoTTF-100A is a device and Bevacizumab is a study drug that have both been approved by the FDA (Food and Drug Administration) for use as monotherapy in treating glioblastoma multiforme. The NovoTTF-l00A is a portable battery operated device which produces TTFields within the human body using surface electrodes (transducer arrays). Intermediate frequency electric fields (TTFields) stunt the growth of tumor cells.

The purpose of this study is to determine the efficacy of the combination of Bevacizumab and NovoTTF-100A in Bevacizumab naive (meaning have never received bevacizumab before) patients with recurrent glioblastoma (GBM) as measured by 6-month progression free survival.


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Biological: Bevacizumab
Device: NovoTTF-l00A
Other: Quality of Life Assessment
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 Prospective Phase II Trial of NovoTTF-100A With Bevacizumab (Avastin) in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Number of patients that achieve progression free survival by Kaplan Meier methodology.


Secondary Outcome Measures:
  • Objective response rate based on RANO Criteria [ Time Frame: 30 days after treatment completion ] [ Designated as safety issue: No ]
    Response will be scored based on a combination of imaging and clinical features as defined by the modified Response Assessment in Neuro-Oncology (RANO) criteria. http://www.iconplc.com/services/imaging/central-imaging-core-lab-/regulatory-expertise/IMI-RANO-Criteria-Booklet-Nov-2011.pdf

  • Number of patients that experience toxicities with this combination of therapies [ Time Frame: 30 days after treatment completion ] [ Designated as safety issue: Yes ]
    Safety and tolerability of combination of bevacizumab and NovoTTF-l00A in this population by CTCAE version 4.0.

  • Median overall survival [ Time Frame: 30 days after treatment completion ] [ Designated as safety issue: No ]
  • To assess time-to-progression [ Time Frame: 30 days after treatment completion ] [ Designated as safety issue: No ]
    Median time to progression by Kaplan Meier methodology.

  • Neurocognitive function (NCF) [ Time Frame: 30 days after treatment completion ] [ Designated as safety issue: No ]
    Time to reliable change (decline) in neurocognitive function by Kaplan Meier methodology. Memory, verbal fluency, visual-motor speed, executive function and motor dexterity tests will be administered.

  • Quality of Life (QOL) [ Time Frame: 30 days after treatment completion ] [ Designated as safety issue: No ]
    Based on the Functional Assessment of Cancer Therapy including Brain Tumor module (FACT-Br) questionnaire


Estimated Enrollment: 40
Study Start Date: June 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab and NovoTTF-100A
Bevacizumab will be administered intravenously on days 1 and 15 of each 28 day cycle.The dose of bevacizumab will be 10 mg/kg of actual body weight.
Biological: Bevacizumab
Bevacizumab will be administered intravenously on days 1 and 15 of each 28 day cycle. The dose of bevacizumab will be 10 mg/kg of actual body weight.
Other Names:
  • Avastin
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • anti-VEGF rhuMAb
  • recombinant humanized anti-VEGF monoclonal antibody
  • rhuMAb VEGF
Device: NovoTTF-l00A
NovoTTF-100A will be worn continuously.
Other Name: electric field therapy
Other: Quality of Life Assessment
Functional Assessment of Cancer Therapy including Brain Tumor module (FACT-Br) questionnaire
Other Name: FACT-Br questionnaire

Detailed Description:

This will be an open label Phase II trial in adults with recurrent glioblastoma (GBM). The NovoTTF-100A treatment and Bevacizumab will be administered on an outpatient basis; NovoTTF-100A treatment will be initiated in the outpatient clinic.

PRIMARY OBJECTIVES:

I. To determine the efficacy of the combination of bevacizumab and NovoTTF-100A in bevacizumab-naive patients with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6).

SECONDARY OBJECTIVES:

I. To assess safety and tolerability of the combination of bevacizumab and Novo-TTF-100A in this patient population.

II. To evaluate overall survival in this population. III. To determine objective response rate (ORR) by modified Revised Assessment in Neuro-Oncology (RANO) criteria in this population.

IV. To assess time-to-progression in this population. V. To assess neurocognitive function (NCF) and quality of life (QOL) in this population.

OUTLINE:

Patients receive bevacizumab intravenously (IV) on days 1 and 15. Patients also undergo electric field therapy with NovoTTF-100A for at least 18 hours daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 28 days.

  Eligibility

Ages Eligible for Study:   22 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologically confirmed glioblastoma or other grade IV malignant glioma (i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy.
  • Patients with up to two prior recurrences are allowed.
  • Karnofsky performance status >/=70.
  • Patients must have the following laboratory values:

    • Absolute neutrophil count (ANC) >/= 1.5 x 109/L
    • Platelets >/= 100 x 109/L
    • Hemoglobin (Hgb) > 9 g/dL
    • Serum total bilirubin: </= 1.5 x ULN
    • ALT and AST </= 3.0 x ULN
    • Serum creatinine </= 1.5 x ULN
    • Blood coagulation parameters: INR </= 1.5
  • Minimum interval since completion of radiation treatment is 12 weeks
  • Minimum interval since last drug therapy:

    • 3 weeks since last non-cytotoxic therapy
    • 3 weeks must have elapsed since the completion of a non-nitrosourea-containing chemotherapy regimen
    • 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen.
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information.
  • Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. The effects of bevacizumab on developing fetus or nursing infant are not known. Female patients of child-bearing potential must have a negative pregnancy test.
  • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission. Patients with other prior malignancies must be disease-free for 2: three years.
  • Patients must be maintained on a stable corticosteroid regimen from the time of their baseline scan until the start of treatment and/or for at least 5 days before starting treatment.

Exclusion Criteria:

  • Patients who have had previous treatment with bevacizumab.
  • Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury </= 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device </=1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
  • Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:

    • History or presence of serious uncontrolled ventricular arrhythmias
    • Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CV A), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)
    • Uncontrolled hypertension (defined by a systolic blood pressure (SBP) >/= 160 mm Hg or diastolic blood pressure (DBP) >/= 100 mm Hg while on anti-hypertensive medications)
  • Patients with cirrhosis, or active viral or nonviral hepatitis.
  • Implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain or documented clinically significant arrhythmias.
  • Infra-tentorial tumor
  • Evidence of increased intracranial pressure (clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
  • Known sensitivity to conductive hydrogels
  • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Pregnant or breast-feeding women
  • Patients unwilling or unable to comply with the protocol
  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: NCT01894061

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Manmeet Ahluwalia, MD    216-444-6145    ahluwam@ccf.org   
Principal Investigator: Manmeet Ahluwalia, MD         
Sponsors and Collaborators
Case Comprehensive Cancer Center
NovoCure Ltd.
Investigators
Study Chair: Manmeet Ahluwalia, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01894061     History of Changes
Other Study ID Numbers: CASE3313, P30CA043703
Study First Received: July 3, 2013
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
recurrent adult brain tumor
Bevacizumab-naive
NovoTTF-100A

Additional relevant MeSH terms:
Glioblastoma
Brain Neoplasms
Gliosarcoma
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
Antibodies
Antibodies, Monoclonal
Bevacizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 14, 2014