MRI-Guided Laser Surgery and Doxorubicin Hydrochloride in Treating Patients With Recurrent Glioblastoma Multiforme

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01851733
First received: May 7, 2013
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

This pilot clinical trial studies magnetic resonance imaging (MRI)-guided laser surgery (MLA) and doxorubicin hydrochloride in treating patients with recurrent glioblastoma multiforme. The blood brain barrier (BBB) is a separation of circulating blood from the tissue of the central nervous system, preventing substances in the blood from entering the brain. MLA disrupts the BBB around the tumor which may allow cancer-killing substances to be carried directly to the tumor and the surrounding area. Using MLA prior to chemotherapy may result in a greater concentration of drug in the tumor to kill the cancer cells while limiting side effects.


Condition Intervention
Glioblastoma
Other: Blood draw - biomarkers
Procedure: MRI-guided Laser Heat Ablation (MLA)
Drug: Doxorubicin
Other: Blood draw - dendritic cells

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: A Pilot Study of Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Doxorubicin in the Treatment of Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Ktrans from DSC-MRI [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Using a 2 compartment model to calculate a the vascular transfer constant (Ktrans) which will provide a quantitative measure of blood brain barrier leakage

  • Peritumoral permeability scores, measured by DSC-MRI and serum biomarkers [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Pearson correlation coefficient (r) will be determined for each biomarker and Ktrans value. A minimum r=0.5 is required for inclusion for further analysis and will be used as a peritumoral permeability score. This score will then be correlated with the patient outcome data to determine whether it has a predictive value.

  • 6-month PFS (rate) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Assessed using RANO Response criteria. A log-rank test will be used to compare 6-PFS of Arm B and of Arm C to historical controls.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Date began MLA treatment to date of death from any cause. A log-rank test will be used to compare OS of Arm B and of Arm C to historical controls.

  • Quality of Life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Using Karnofsky performance status and the mini-mental state evaluation to assess patient overall response to treatment.


Estimated Enrollment: 45
Study Start Date: August 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm A: Control

Patients undergo biopsy per standard of care diagnostic purposes.

Biomarker blood draws will be drawn at different time points.

Other: Blood draw - biomarkers

Arm A:

  • before biopsy (up to 3 days before)
  • within approximately 3 days after biopsy
  • 2 weeks after biopsy
  • 4 weeks after biopsy

Arm B:

  • before MLA (up to 3 days before)
  • within 3 days after MLA
  • 1 week after MLA
  • 2 weeks after MLA
  • 3 weeks after MLA
  • 4 weeks after MLA
  • 5 weeks after MLA
  • 6 weeks after MLA
  • 10 weeks after MLA ONLY IF the 6-week post-MLA scan shows prolonged disruption of the BBB
  • 14 weeks after MLA
  • every 8 weeks thereafter until progression

Arm C:

  • before MLA (up to 3 days before)
  • within 3 days after MLA
  • weekly before (on the same day as) chemotherapy
  • weekly within 24 hours after chemotherapy
  • 10 weeks after MLA ONLY IF the 6-week post-MLA scan shows prolonged disruption of the BBB
  • 14 weeks after MLA
  • every 8 weeks thereafter until progression
Other: Blood draw - dendritic cells

Arm A:

  • before biopsy (up to 3 days before)
  • 2 weeks after biopsy
  • 4 weeks after biopsy
  • every 2 weeks thereafter for up to 3 months after biopsy (provided there is no significant chemotherapy induced cytopenia)

The second 10 patients enrolled to Arm B:

  • before MLA (up to 3 days before)
  • 2 weeks after MLA
  • 4 weeks after MLA
  • every 2 weeks thereafter for up to 3 months after biopsy (provided there is no significant chemotherapy induced cytopenia)
Experimental: Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)

Patients undergo MLA (MRI-guided laser heat ablation). A subset of patients will have a biopsy at time of MLA.

Beginning 6-8 weeks later, patients receive doxorubicin hydrochloride 20 mg/m2 intravenously (IV) over 5 minutes once weekly for 6 weeks.

Biomarker blood draws will be drawn at different time points.

Other: Blood draw - biomarkers

Arm A:

  • before biopsy (up to 3 days before)
  • within approximately 3 days after biopsy
  • 2 weeks after biopsy
  • 4 weeks after biopsy

Arm B:

  • before MLA (up to 3 days before)
  • within 3 days after MLA
  • 1 week after MLA
  • 2 weeks after MLA
  • 3 weeks after MLA
  • 4 weeks after MLA
  • 5 weeks after MLA
  • 6 weeks after MLA
  • 10 weeks after MLA ONLY IF the 6-week post-MLA scan shows prolonged disruption of the BBB
  • 14 weeks after MLA
  • every 8 weeks thereafter until progression

Arm C:

  • before MLA (up to 3 days before)
  • within 3 days after MLA
  • weekly before (on the same day as) chemotherapy
  • weekly within 24 hours after chemotherapy
  • 10 weeks after MLA ONLY IF the 6-week post-MLA scan shows prolonged disruption of the BBB
  • 14 weeks after MLA
  • every 8 weeks thereafter until progression
Procedure: MRI-guided Laser Heat Ablation (MLA) Drug: Doxorubicin
Other Name: Adriamycin®
Other: Blood draw - dendritic cells

Arm A:

  • before biopsy (up to 3 days before)
  • 2 weeks after biopsy
  • 4 weeks after biopsy
  • every 2 weeks thereafter for up to 3 months after biopsy (provided there is no significant chemotherapy induced cytopenia)

The second 10 patients enrolled to Arm B:

  • before MLA (up to 3 days before)
  • 2 weeks after MLA
  • 4 weeks after MLA
  • every 2 weeks thereafter for up to 3 months after biopsy (provided there is no significant chemotherapy induced cytopenia)
Experimental: Arm C: (MLA, doxorubicin hydrochloride at 72 hours)

Patients undergo MLA (MRI-guided laser heat ablation).

Beginning within 72 hours later, patients receive doxorubicin hydrochloride 20 mg/m2 IV over 5 minutes once weekly for 6 weeks.

Biomarker blood draws will be drawn at different time points.

Other: Blood draw - biomarkers

Arm A:

  • before biopsy (up to 3 days before)
  • within approximately 3 days after biopsy
  • 2 weeks after biopsy
  • 4 weeks after biopsy

Arm B:

  • before MLA (up to 3 days before)
  • within 3 days after MLA
  • 1 week after MLA
  • 2 weeks after MLA
  • 3 weeks after MLA
  • 4 weeks after MLA
  • 5 weeks after MLA
  • 6 weeks after MLA
  • 10 weeks after MLA ONLY IF the 6-week post-MLA scan shows prolonged disruption of the BBB
  • 14 weeks after MLA
  • every 8 weeks thereafter until progression

Arm C:

  • before MLA (up to 3 days before)
  • within 3 days after MLA
  • weekly before (on the same day as) chemotherapy
  • weekly within 24 hours after chemotherapy
  • 10 weeks after MLA ONLY IF the 6-week post-MLA scan shows prolonged disruption of the BBB
  • 14 weeks after MLA
  • every 8 weeks thereafter until progression
Procedure: MRI-guided Laser Heat Ablation (MLA) Drug: Doxorubicin
Other Name: Adriamycin®

Detailed Description:

Evaluate imaging techniques (MRI) and blood tests (biomarkers) to help figure out the best time for chemotherapy to be initiated after the blood brain barrier is disrupted, as it is immediately following a procedure like MRI-guided laser ablation (MLA-Monteris Neuroblate).

  Eligibility

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

Inclusion Criteria - Arm A:

  • Newly diagnosed brain tumors that appear high-grade based on MRI.
  • Scheduled for biopsy for diagnostic purposes.
  • At least 18 years of age.
  • Ability to understand and willingness to sign an IRB-approved written informed consent document.

Exclusion Criteria - Arm A:

  • Currently receiving or scheduled to receive any other therapies intended to treat the newly diagnosed high grade glioma prior to the biopsy and the post-biopsy biomarker sample collection and immune monitoring sample collection.
  • Pregnant.
  • Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.

Inclusion Criteria - Arms B and C:

  • Histologically confirmed GBM; rare GBM variants, secondary GBM, and suspected secondary GBM are allowed.
  • Unequivocal evidence of tumor progression by magnetic resonance imaging (MRI) scan.
  • There must be an interval of at least 12 weeks from the completion of radiotherapy to study registration except if there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks from the completion of radiotherapy, the use of PET scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudoprogression.
  • Largest dimension of the recurrent tumor is a maximum of approximately 3 cm.
  • At least 18 years of age.
  • Karnofsky performance status ≥ 60%.
  • Scheduled for MRI-guided Laser Ablation (MLA).
  • Normal left ventricular ejection fraction on MUGA or echocardiogram within the past 1 year prior to registration for patients with history of congestive heart failure and/or coronary disease requiring medications other than aspirin, or known prior exposure to anthracycline chemotherapy.
  • Adequate bone marrow and hepatic function as defined below (must be within 7 days of MLA):

    • Absolute neutrophil count (ANC) ≥ 1500/mcl (G-CSF is allowed)
    • Platelets ≥ 100,000/mcl
    • Hemoglobin ≥ 9 (pRBC transfusion +/- ESA are allowed)
    • ALT ≤ 3 x ULN
    • AST ≤ 3 x ULN
    • ALP ≤ 3 x ULN. If ALP is > 3 x ULN, GGT must be checked and be ≤ 3 x ULN.
    • Bilirubin ≤ 2 x ULN
  • At the time of registration, patient must have recovered from the toxic effects of prior therapy to no more than grade 1 toxicity.
  • At the time of registration, patient must be at least 2 weeks from prior vincristine, 3 weeks from prior procarbazine, and 4 weeks from other prior cytotoxic chemotherapy.
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria - Arms B and C:

  • Prior treatment with doxorubicin and/or bevacizumab.
  • Prior treatment with Gliadel wafer is allowed if it has been at least 3 months from placement.
  • Previous treatment with complete cumulative doses of daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones that is equivalent to a total dose of 240 mg/m2 doxorubicin.
  • More than 2 prior relapses.
  • Currently receiving any other investigational agents that are intended as treatments of GBM.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to doxorubicin or other agents used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recent heart attack within the previous 12 months or severe heart problems, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant and/or breastfeeding. Premenopausal women must have a negative serum pregnancy test within 14 days of study entry.
  • Inability to undergo MRI due to personal and medical reasons.
  • Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.
  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: NCT01851733

Contacts
Contact: David Tran, M.D., Ph.D. 314-362-5677 dtran@dom.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: David Tran, M.D., Ph.D.    314-362-5677    dtran@dom.wustl.edu   
Sub-Investigator: Eric Leuthardt, M.D.         
Sub-Investigator: Joshua Shimony, M.D., Ph.D.         
Sub-Investigator: Michael Chicoine, M.D.         
Sub-Investigator: Albert Kim, M.D., Ph.D.         
Sub-Investigator: Ralph Dacey, M.D.         
Sub-Investigator: Joshua Dowling, M.D.         
Sub-Investigator: Gerald Linette, M.D., Ph.D.         
Sub-Investigator: Gregory Zipfel, M.D.         
Sub-Investigator: Gavin Dunn, M.D., Ph.D.         
Sub-Investigator: Keith Rich, M.D., Ph.D.         
Sub-Investigator: Clifford Robinson, M.D.         
Sub-Investigator: Joseph Simpson, M.D., Ph.D.         
Sub-Investigator: Jiayi Huang, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: David Tran, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01851733     History of Changes
Other Study ID Numbers: 201305148
Study First Received: May 7, 2013
Last Updated: June 23, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014