Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.

Condition or disease Intervention/treatment Phase
IDH Family Wildtype Recurrent Anaplastic Astrocytoma Recurrent Glioblastoma Procedure: Laser Interstitial Thermal Therapy Drug: Lomustine Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Laser Interstitial Thermal Therapy (LITT) in Recurrent Glioblastoma
Actual Study Start Date : November 7, 2017
Estimated Primary Completion Date : November 1, 2021
Estimated Study Completion Date : November 1, 2021


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Incidence of toxicity [ Time Frame: Up to 4 years ]
    Will be summarized by frequency tables.

  9. Long-term steroid requirements [ Time Frame: Up to 4 years ]
    Will be summarized by frequency tables.

  10. 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03022578


Contacts
Layout table for location contacts
Contact: Barbara J. O'Brien 713-792-2883 bjobrien@mdanderson.org

Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Barbara J. O'Brien    713-792-2883      
Principal Investigator: Barbara J. O'Brien         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Barbara J O'Brien M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03022578     History of Changes
Other Study ID Numbers: 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 )
First Posted: January 16, 2017    Key Record Dates
Last Update Posted: September 27, 2019
Last Verified: September 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for 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
Lomustine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents