Study Bendamustine Concurrent Whole Brain Radiation Brain Metastases From Solid Tumors - Full Text View

Sponsor:	H. Lee Moffitt Cancer Center and Research Institute
Collaborators:	National Comprehensive Cancer Network Cephalon
Information provided by (Responsible Party):	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT00879073

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:

MedlinePlus related topics: Cancer

Drug Information available for: Bendamustine hydrochloride Bendamustine

U.S. FDA Resources

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

Estimated Enrollment:	24
Study Start Date:	April 2009
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	August 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 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00879073

Contacts

Contact: Pam A. Smith, CCRP

813-745-3951

pam.smith@moffitt.org

Locations

United States, Florida
H. Lee Moffitt Cancer Center & Research Institute	Recruiting
Tampa, Florida, United States, 33612
Contact: Pamela Smith, CCRP 813-745-3951 pam.smith@moffitt.org
Principal Investigator: Edward Pan, M.D.
Sub-Investigator: Margaret Booth-Jones, Ph.D.
Sub-Investigator: Prakash Chinnaiyan, M.D.
Sub-Investigator: Michael Yu, M.D.
Sub-Investigator: Peter Forsyth, M.D.

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:

Moffitt Cancer Center Clinical Trials website This link exits the ClinicalTrials.gov site

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:	February 21, 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
Neoplasms, Second Primary
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
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 24, 2012