Study Bendamustine Concurrent Whole Brain Radiation Brain Metastases From Solid Tumors

Phase I Study of Bendamustine With Concurrent Whole Brain Radiation Therapy in Patients With Brain Metastases From Solid Tumors

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.

Study Overview

• Status: Terminated
• Conditions: Brain Metastases
• Intervention / Treatment: Drug: Bendamustine

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A - Cohort 1 Treatment; Cohort 1: Bendamustine 60 mg/m² x 4 weeks	Drug: Bendamustine; Approximately 15-24 study patients will be enrolled in this Phase I trial. Study patients will receive a weekly dose of IV bendamustine with whole brain radiation therapy for 3 weeks and then receive a fourth dose of IV bendamustine one week after completion of whole brain radiation therapy. The first dose of IV bendamustine will be given when whole brain radiation is initiated.; Other Names: Treanda
Experimental: B - Cohort 2 Treatment; Cohort 2: Bendamustine 80 mg/m² x 4 weeks	Drug: Bendamustine; Approximately 15-24 study patients will be enrolled in this Phase I trial. Study patients will receive a weekly dose of IV bendamustine with whole brain radiation therapy for 3 weeks and then receive a fourth dose of IV bendamustine one week after completion of whole brain radiation therapy. The first dose of IV bendamustine will be given when whole brain radiation is initiated.; Other Names: Treanda
Experimental: C - Cohort 3 Treatment; Cohort 3: Bendamustine 100 mg/m² x 4 weeks	Drug: Bendamustine; Approximately 15-24 study patients will be enrolled in this Phase I trial. Study patients will receive a weekly dose of IV bendamustine with whole brain radiation therapy for 3 weeks and then receive a fourth dose of IV bendamustine one week after completion of whole brain radiation therapy. The first dose of IV bendamustine will be given when whole brain radiation is initiated.; Other Names: Treanda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	To determine the MTD of bendamustine in combination with WBRT	24 Weeks per Patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	To determine the toxicity profile of bendamustine in combination with WBRT	24 Weeks per Patient

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: National Comprehensive Cancer Network; Cephalon

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: April 8, 2009
• First Submitted That Met QC Criteria: April 8, 2009
• First Posted (Estimate): April 9, 2009

Study Record Updates

• Last Update Posted (Estimate): December 18, 2012
• Last Update Submitted That Met QC Criteria: December 17, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Brain and Nervous System
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Bendamustine Hydrochloride
• Other Study ID Numbers: MCC-15690