Clinical trial NCT00879073: Study Bendamustine Concurrent Whole Brain Radiation Brain Metastases From Solid Tumors
Official title: Phase I Study of Bendamustine With Concurrent Whole Brain Radiation Therapy in Patients With Brain Metastases From Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Brain Metastases
Keywords: Brain and Nervous System
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
name: Cephalon
First posted: 2009-04-09
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to:

* Test the maximum tolerated dose (MTD) of Bendamustine with whole brain radiation therapy (WBRT)
* To determine the plasma pharmacokinetics (a blood test to see how much of the drug is getting into the patient's system and how long it lasts in the system) of Bendamustine
* To determine the presence of Bendamustine in cerebrospinal fluid (CSF) (fluid from the brain and spinal cord) of study patients Bendamustine is approved by the Food and Drug Administration (FDA) for chronic lymphocytic leukemia. However, Bendamustine will be used in this study as an investigational agent.

Detailed description: Bendamustine will be started in the first group at a dose of 60 mg/m²; patients in group 2 will be given Bendamustine at a dose of 80 mg/m²; patients in Group 3 will be given Bendamustine at 100 mg/m². Each cohort will receive Bendamustine once weekly for a total of 4 weeks.

Approximately 3-6 patients enrolled in this study will receive lumbar punctures. Patients will be told before study enrollment whether they will have a lumbar puncture to withdraw CSF.

Eligibility criteria: Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy within 5 years of registration. Pathological confirmation by pathologists at Moffitt Cancer Center is required.
* Cerebral metastases from known solid tumors diagnosed by contrast-enhanced brain magnetic resonance imaging (MRI) or contrast-enhanced head computed tomography (CT) for patients unable to receive MRIs
* Single metastases that have been resected
* Patient may have had prior radiosurgery or surgical resection for brain metastasis. Patients should have completed prior therapy at least 14 days but no longer than 56 days prior to study entry.
* Karnofsky Performance Status ≥ 70 within 28 days prior to study entry.
* Expected life span of ≥ 3 months
* Able to tolerate 3 week course of whole brain radiation therapy
* Able to receive a lumbar puncture (for post-MTD patients only)
* Adequate bone marrow, liver and renal function as assessed by the following: Hemoglobin \> 9.0 g/dl; Absolute neutrophil count (ANC) \> 1,500/mm³; Platelet count \> 100,000/mm³; Total bilirubin \< 1.5 x upper limit of normal (ULN); Alanine transaminase/Aspartic transaminase (ALT/AST) \< 2.5 x the ULN (\< 5 x ULN for patients with liver involvement); International normalized ratio (INR) \< 1.5 or a prothrombin time/partial thromboplastin time (PT/PTT) within normal limits; Creatinine \< 1.5 x ULN
* Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
* Ability to understand and sign a study-specific written informed consent prior to study entry.
* Patients receiving systemic therapy are eligible for this study if given \>14 days prior to study entry and given no sooner than \>14 days post radiation therapy (RT) completion.
* Complete history and general physical examination within 28 days prior to study entry

Exclusion Criteria:

* Known hypersensitivity to bendamustine or mannitol
* Patients with cerebral metastases from unknown primary tumors
* Patients with cerebral metastases from leukemias or lymphomas
* Patients with uncontrolled systemic cancer (i.e. evidence of systemic disease progression \< 3 months prior to study entry)
* Systemic chemotherapy ≤14 days prior to study entry or ≤14 days after completing radiotherapy
* Patients who received prior BCNU wafer (Gliadel®) implantation for surgically resected cerebral metastatic lesions
* Patients with a life expectancy of less than 3 months
* Patients who received prior whole brain radiation therapy. As noted above, patients who received prior radiosurgery are allowed
* Patients with significant hydrocephalous
* Active clinically serious infection \> Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
* Pregnant or lactating women

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 24 Weeks per Patient
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 24 Weeks per Patient
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Edward Pan, M.D.
role: PRINCIPAL_INVESTIGATOR
References: