Study Bendamustine Concurrent Whole Brain Radiation Brain Metastases From Solid Tumors

This study has been terminated.
(Principal Investigator is leaving Moffitt)
Sponsor:
Collaborators:
National Comprehensive Cancer Network
Cephalon
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00879073
First received: April 8, 2009
Last updated: December 17, 2012
Last verified: December 2012
  Purpose

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.

Condition Intervention Phase
Brain Metastases
Drug: Bendamustine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Bendamustine With Concurrent Whole Brain Radiation Therapy in Patients With Brain Metastases From Solid Tumors

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 24 Weeks per Patient ] [ Designated as safety issue: No ]
    To determine the MTD of bendamustine in combination with WBRT


Secondary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) [ Time Frame: 24 Weeks per Patient ] [ Designated as safety issue: Yes ]
    To determine the toxicity profile of bendamustine in combination with WBRT


Enrollment: 12
Study Start Date: April 2009
Study Completion Date: December 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Treanda

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00879073

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
National Comprehensive Cancer Network
Cephalon
Investigators
Principal Investigator: Edward Pan, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00879073     History of Changes
Other Study ID Numbers: MCC-15690
Study First Received: April 8, 2009
Last Updated: December 17, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Brain and Nervous System

Additional relevant MeSH terms:
Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Bendamustine
Nitrogen Mustard Compounds
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014