Clinical trial NCT01894061: NovoTTF-100A With Bevacizumab (Avastin) in Patients With Recurrent Glioblastoma
Official title: A Prospective Phase II Trial of NovoTTF-100A With Bevacizumab (Avastin) in Patients With Recurrent Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Keywords: adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
recurrent adult brain tumor
Bevacizumab-naive
NovoTTF-100A
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: NovoCure Ltd.
First posted: 2013-07-09
Enrollment: 25
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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 10\^9/L
  * Platelets ≥ 100 x 10\^9/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 ≥ 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, and or NovoTTF 100A system.
* 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 (CVA), 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
* Patients with leptomeningeal disease

Primary outcomes:
measure: Percent of Participants With 6-month Progression-free Survival (PFS6)
timeFrame: 6 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Based on RANO Criteria
timeFrame: 30 days after treatment completion through study completion, an average of 5 years, 9 months
measure: Number of Participants Experiencing Grade 3/4 Toxicities Related to Therapy Combination Per by CTCAE Version 4.0.
timeFrame: 5 years, 9 months
measure: Median Overall Survival
timeFrame: 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
measure: Median Time-to-progression
timeFrame: 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
measure: Time to Reliable Change in Neurocognitive Function (NCF)
timeFrame: 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
measure: Change From Baseline in Quality of Life (QOL) as Measured by FACT-BR Score
timeFrame: Baseline, 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
measure: Percent of Participants With 12-month Progression-free Survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: David Peereboom, MD
role: PRINCIPAL_INVESTIGATOR
References: