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Laser Interstitial Thermal Therapy and Lomustine in Treating Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03022578
Recruitment Status : Recruiting
First Posted : January 16, 2017
Last Update Posted : September 27, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE January 13, 2017
First Posted Date  ICMJE January 16, 2017
Last Update Posted Date September 27, 2019
Actual Study Start Date  ICMJE November 7, 2017
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • Disease control rate [ Time Frame: At 6 months ]
    Simon's optimal two-stage design will be employed to evaluate the effect of the study regimen on disease control rate at 6 months. Will be estimated along with 95% confidence intervals.
  • Clinical characteristics [ Time Frame: Up to 4 years ]
    Will be summarized using standard descriptive statistics, such as mean, standard deviation, median, and range for continuous variables, frequency and proportion for categorical variables. Correlation will be assessed among continuous variables using Pearson or Spearman correlation coefficient, whichever is appropriate. Association between categorical variables will be examined by Chi-Squared test or Fisher's exact test when appropriate. Wilcoxon rank-sum test or Kruskal-Wallis test will be used to examine the difference on continuous variables between or among patient's characteristic groups.
  • Length of hospital stay [ Time Frame: Up to 4 years ]
    Will be summarized using standard descriptive statistics, such as mean, standard deviation, median, and range for continuous variables, frequency and proportion for categorical variables. Correlation will be assessed among continuous variables using Pearson or Spearman correlation coefficient, whichever is appropriate. Association between categorical variables will be examined by Chi-Squared test or Fisher's exact test when appropriate. Wilcoxon rank-sum test or Kruskal-Wallis test will be used to examine the difference on continuous variables between or among patient's characteristic groups.
  • Biomarkers in peripheral blood and tumor tissue [ Time Frame: Up to 4 years ]
    Will be summarized using standard descriptive statistics, such as mean, standard deviation, median, and range for continuous variables, frequency and proportion for categorical variables. Correlation will be assessed among continuous variables using Pearson or Spearman correlation coefficient, whichever is appropriate. Association between categorical variables will be examined by Chi-Squared test or Fisher's exact test when appropriate. Wilcoxon rank-sum test or Kruskal-Wallis test will be used to examine the difference on continuous variables between or among patient's characteristic groups.
  • Inflammatory/immunologic profile [ Time Frame: Up to 4 years ]
    Will be summarized using standard descriptive statistics, such as mean, standard deviation, median, and range for continuous variables, frequency and proportion for categorical variables. Correlation will be assessed among continuous variables using Pearson or Spearman correlation coefficient, whichever is appropriate. Association between categorical variables will be examined by Chi-Squared test or Fisher's exact test when appropriate. Wilcoxon rank-sum test or Kruskal-Wallis test will be used to examine the difference on continuous variables between or among patient's characteristic groups.
  • Overall survival (OS) [ Time Frame: Up to 4 years ]
    Will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on OS.
  • Time to progression (TTP) [ Time Frame: Up to 4 years ]
    Will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on TTP.
  • Incidence of toxicity [ Time Frame: Up to 4 years ]
    Will be summarized by frequency tables.
  • Long-term steroid requirements [ Time Frame: Up to 4 years ]
    Will be summarized by frequency tables.
  • MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) data [ Time Frame: Up to 4 years ]
    Will summarize the MDASI-BT at each time point using descriptive statistics and evaluate the change of MDASI-BT over time and its correlation with response and/or treatment tolerance using linear mixed models, where random effects will be used to account for within-subject correlations.
Original Primary Outcome Measures  ICMJE
 (submitted: January 13, 2017)
Disease control rate [ Time Frame: 6 months ]
Disease control rate at defined as the percentage of evaluable patients that have at least stable disease or better at 6 months after the LITT procedure. RANO criteria used to determine progression.
Change History Complete list of historical versions of study NCT03022578 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Laser Interstitial Thermal Therapy and Lomustine in Treating Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma
Official Title  ICMJE Phase II Study of Laser Interstitial Thermal Therapy (LITT) in Recurrent Glioblastoma
Brief Summary This phase II trial studies how well laser interstitial thermal therapy and lomustine work in treating patients with glioblastoma or anaplastic astrocytoma that has come back. Using laser to heat the tumor cells may help to kill them. Drugs used in chemotherapy, such as lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving laser interstitial thermal therapy and lomustine may work better in treating patients with glioblastoma or anaplastic astrocytoma.
Detailed Description

PRIMARY OBJECTIVES:

I. Determine the disease control rate at 6 months in patients with recurrent glioblastoma or isocitrate dehydrogenase (IDH)-wildtype anaplastic astrocytoma treated with Laser Interstitial Thermal Therapy (LITT) at recurrence, followed by salvage chemotherapy.

SECONDARY OBJECTIVES:

I. Estimate overall survival (OS) of patients with recurrent glioblastoma, or isocitrate dehydrogenase (IDH)-wildtype anaplastic astrocytoma treated with LITT at tumor recurrence, followed by salvage chemotherapy.

II. Estimate time to progression (TTP) of patients with recurrent glioblastoma, or isocitrate dehydrogenase (IDH)-wildtype anaplastic astrocytoma that are treated with LITT at tumor recurrence, followed by salvage chemotherapy.

III. Analyze volumetric data consisting of thermal damage threshold lines and overall tumor volume to determine any role of 'extent of ablation' in outcomes (OS and/or TTP).

IV. Characterize the safety profile of LITT followed by treatment with lomustine chemotherapy in the recurrent disease setting, using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

V. Assess the long-term steroid requirements following LITT, compared to historical controls.

VI. Determine the radiographic evolution of LITT-treated glioblastoma over time, using conventional magnetic resonance imaging (MRI) (T1 pre and post-contrast images, T2-weighted images [T2WI], fluid attenuating inversion recovery [FLAIR] images) and advanced brain tumor imaging (ABTI) [magnetic resonance (MR) perfusion [dynamic susceptibility contrast (DSC), dynamic contrast enhancement (DCE) and arterial spin labeling (ASL)], MR-diffusion, and MR spectroscopy), to include quantitative tumor metrics (volumetric extent of ablation and Response Assessment in Neuro-Oncology [RANO] criteria).

VII. Analyze health care utilization as measured by length of hospital stay following LITT (including inpatient rehabilitation care).

VIII. Evaluate patients' functional status (using the Karnofsky performance score [KPS] and the occurrence of symptoms [using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT[English])] self-reporting tool), and correlate to disease progression and tolerance to treatment.

EXPLORATORY OBJECTIVES:

I. Identify correlative tumor and peripheral blood molecular markers that impact outcomes, etc, and identify inflammatory/immunologic markers to assess neoantigen expression, etc, if sufficient tissue is available.

II. Identify and characterize changes in tumor tissue following LITT, by analyzing and comparing pre- and post-procedure tissue samples, if sufficient tissue is available.

OUTLINE:

Patients undergo LITT at baseline and receive lomustine orally (PO) on day 1. Treatment with lomustine repeats every 42 days for up to 6 cycles in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up every 3 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • IDH Family Wildtype
  • Recurrent Anaplastic Astrocytoma
  • Recurrent Glioblastoma
Intervention  ICMJE
  • Procedure: Laser Interstitial Thermal Therapy
    Undergo LITT
    Other Name: LITT
  • Drug: Lomustine
    Given PO
    Other Names:
    • 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
    • 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-
    • Belustin
    • Belustine
    • CCNU
    • Cecenu
    • CeeNU
    • Chloroethylcyclohexylnitrosourea
    • Citostal
    • Gleostine
    • Lomeblastin
    • Lomustinum
    • Lucostin
    • Lucostine
    • N-(2-Chloroethyl)-N''-cyclohexyl-N-nitrosourea
    • Prava
    • RB-1509
    • WR-139017
Study Arms  ICMJE Experimental: Treatment (LITT, lomustine)
Patients undergo LITT at baseline and receive lomustine PO on day 1. Treatment with lomustine repeats every 42 days for up to 6 cycles in the absence of disease progression or unaccepted toxicity.
Interventions:
  • Procedure: Laser Interstitial Thermal Therapy
  • Drug: Lomustine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 12, 2017)
34
Original Estimated Enrollment  ICMJE
 (submitted: January 13, 2017)
37
Estimated Study Completion Date  ICMJE November 1, 2021
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have histologically-proven, recurrent supratentorial grade IV glioblastoma (or grade III IDH-wildtype anaplastic astrocytoma), for which a complete surgical resection is unsafe due to location, shape, or size of the tumor. Diagnosis of recurrence will be established by biopsy and frozen section immediately prior to initiating LITT procedure. If findings on frozen section are not consistent with recurrence (glioblastoma or recurrent IDH-wildtype anaplastic astrocytoma), decision to proceed with LITT procedure will be at the discretion of the neurosurgeon (only patients with histologically-proven recurrent tumor will be evaluable for efficacy).
  • All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information. Patients must be registered prior to treatment on study.
  • Patients must have a Karnofsky performance score (KPS) > 60.
  • Patients must have received standard of care therapy with chemoradiation with temozolomide followed by adjuvant chemotherapy with temozolomide. Patients may have received one additional chemotherapy regimen (other than lomustine) in addition to adjuvant temozolomide prior to study entry (patients at either first or second recurrence are eligible).
  • In the context of this clinical trial, a lesion suitable for LITT is single, enhancing, supratentorial, at least 2 cm from inner table of skull over the hemispheric convexity, and > 1 cm, but < 4 cm in cross-sectional dimension, including thalamic tumor (=< 3 cm).
  • Patients must have stable cardiovascular, neurovascular and neurological status, and be considered surgical candidates, as determined by any relevant pre-operative assessments, at the neurosurgeon's discretion.
  • Patients must not be receiving concurrent anti-tumor treatment and must have recovered from toxicity of prior treatment. Minimum interval required: 1) > 6 weeks following nitrosourea chemotherapy; 2) > 4 weeks after recovering from any non-nitrosourea drug or systemic investigational agent; 3) > 2 weeks after receiving any non-cytotoxic anti-tumor drug; 4) > 4 weeks after receiving radiation therapy (> 12 weeks following upfront concurrent chemoradiation); 5) > 2 weeks following Optune device use.
  • Patients must not have previously undergone an intracranial LITT procedure.
  • White blood cell (WBC) > 3,000/ul (performed within 14 days (+ 3 working days) prior to registration)
  • Absolute neutrophil count (ANC) > 1,500/mm^3 (performed within 14 days (+ 3 working days) prior to registration)
  • Platelet count of > 100,000/mm^3 (may be reached by transfusion) (performed within 14 days (+ 3 working days) prior to registration)
  • Hemoglobin > 10 gm/dl (may be reached by transfusion) (performed within 14 days (+ 3 working days) prior to registration)
  • Serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin < 2 times upper limit of normal (ULN) (erformed within 14 days (+ 3 working days) prior to registration)
  • Creatinine < 1.5 mg/dL (performed within 14 days (+ 3 working days) prior to registration)
  • Women of childbearing potential must have a negative B-Human chorionic gonadotropin (HCG) documented within 7 days prior to registration and must agree to practice adequate contraception as defined below. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), includes any female who has had:

    • A hysterectomy
    • A bilateral oophorectomy
    • A bilateral tubal ligation
    • Is post-menopausal: Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >= 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40 pg/mL (< 140 pmol/L).
  • Subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT.
  • Childbearing potential includes any female who has had a negative serum pregnancy test within 7 days of study registration, and agrees to use adequate contraception. Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:

    • Complete abstinence from sexual intercourse for 14 days before starting treatment, through the treatment, and for at least 1 month after the last dose of temozolomide
    • Oral contraceptive, either combined or progestogen alone. A second barrier method is required during the first month of treatment with oral contraceptives
    • Injectable progesterone
    • Implants of levonorgestrel
    • Estrogenic vaginal ring
    • Percutaneous contraceptive patches
    • Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year
    • Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject
    • Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository). Female participants who are lactating should discontinue nursing prior to the first dose of temozolomide and should refrain from nursing throughout the treatment period and for 42 days following the last dose of lomustine.

Exclusion Criteria:

  • Patients must not have received prior treatment with bevacizumab.
  • Patients must not have had prior treatment of glioblastoma with stereotactic radiosurgery, brachytherapy, or carmustine-impregnated wafers (Gliadel).
  • Patients must not have symptoms attributed to mass effect of the tumor (despite corticosteroid treatment) that would be better treated with debulking surgery, or wherein surgical debulking in the first 30 days following LITT procedure would be anticipated for symptom management.
  • Patients unable to undergo MRI are not eligible.
  • Patients with progression of multifocal tumors or tumors involving the posterior fossa (brainstem and cerebellum) will be excluded, as will patients where the anticipated treatment margin will be within 5 mm of critical intracranial structures (e.g., primary branches of cerebral vessels, dural sinuses, hypophysis or cranial nerves).
  • Patients may not have undergone previous treatment with lomustine.
  • Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
  • Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
  • Patients must not have active infection or serious intercurrent medical illness.
  • Patients must not be pregnant/breast feeding and must agree to practice adequate contraception.
  • Patients must not have uncontrolled hypertension (systolic >180 mm hg or diastolic > 100 mg Hg), angina pectoris, cardiac dysrhythmia, or recent (within 6 weeks) intracranial hemorrhage.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Barbara J. O'Brien 713-792-2883 bjobrien@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03022578
Other Study ID Numbers  ICMJE 2016-0443
NCI-2018-01286 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0443 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Barbara J O'Brien M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP