Trial Outcomes & Findings for Laser Interstitial Thermal Therapy and Lomustine in Treating Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma (NCT NCT03022578)

Last Updated: 2022-08-10

Results Overview

Stable Disease per RANO occurs if the patient does not qualify for response or progression and requires stable non enhancing lesions, same/lower dose of corticosteroids, and clinical stability. Complete Response per RANO requires complete disappearance of all enhancing measurable and nonmeasurable disease for at least 4 weeks; no new lesions; and stable/improved nonenhancing lesions, off corticosteroids (or on physiologic replacement dose) and clinical improvement/stability. Partial Response per RANO requires ≥50% decrease of enhancing lesions compared with baseline, sustained for at least 4 weeks; no progression of nonmeasurable disease; no new lesions; stable/improved nonenhancing lesions, same/lower dose of corticosteroids not greater than the dose at time of the baseline scan and clinically improved/stable.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

At 6 months

Results posted on

2022-08-10

Participant Flow

7 Participants signed consent, 3 participants inevaluable due to screen failure

Participant milestones

Participant milestones
Measure	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. Laser Interstitial Thermal Therapy: Undergo LITT Lomustine: Given PO
Overall Study STARTED	4
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Laser Interstitial Thermal Therapy: Undergo LITT Lomustine: Given PO
Overall Study Adverse Event	1
Overall Study Lack of Efficacy	2
Overall Study Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (LITT, Lomustine) n=4 Participants 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. Laser Interstitial Thermal Therapy: Undergo LITT Lomustine: Given PO
Age, Continuous	57 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants

PRIMARY outcome

Timeframe: At 6 months

Outcome measures

Outcome measures
Measure	Treatment (LITT, Lomustine) n=4 Participants 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. Laser Interstitial Thermal Therapy: Undergo LITT Lomustine: Given PO
Disease Control Rate at 6 Months Progression Disease	2 Participants
Disease Control Rate at 6 Months Partial Response	1 Participants
Disease Control Rate at 6 Months Non Evaluable	1 Participants

SECONDARY outcome

Timeframe: From date of enrollment in study to the date of first observation of progressive disease, death due to disease (event), or early discontinuation of treatment, approximately 3 years 3 months

Progression disease per the Response Assessment in Neuro-Oncology (RANO) is defined by any of the following: ≥25% increase in the sum of the products of perpendicular diameters of enhancing lesions (compared with baseline if no decrease) on stable or increasing doses of corticosteroids; a significant increase in T2/FLAIR nonenhancing lesions on stable or increasing doses of corticosteroids compared with the baseline scan or the best response after initiation of therapy, not due to comorbid events; the appearance of any new lesions; clear progression of nonmeasurable lesions; or definite clinical deterioration not attributable to other causes apart from the tumor or to a decrease in the corticosteroid dose.

Outcome measures

Outcome measures
Measure	Treatment (LITT, Lomustine) n=4 Participants 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. Laser Interstitial Thermal Therapy: Undergo LITT Lomustine: Given PO
Time to Progression (TTP)	30 weeks Interval 1.0 to 63.0

SECONDARY outcome

Timeframe: Up to 4 years

Population: Data were not collected.

Will be summarized by frequency tables.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at baseline, after procedure, and with every imaging visit thereafter, up to 4 years

Population: Data were not collected.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: approximately 3 years 3 months

Safety and toxicity of LITT by determination of adverse events and surgical complications within 2 weeks of the procedure, plus an additional 4 weeks (to account for potential delayed inflammatory changes and initiation of subsequent treatment). Safety for LITT procedure will be defined as the absence of severe clinical toxicity as determined by the CTCAE version 4.0, within 6 weeks of the procedure, and/or absence of acute events (ie, significant hemorrhage or brain herniation) documented on imaging. Severe toxicity will also be defined as a drop of 20 points or more in KPS and not amenable to corticosteroids, and likely attributable to the procedure, or symptomatic hemorrhage, increased brain edema resulting in herniation/impending herniation, and/or significant neurologic decline not amenable to corticosteroids. Safety and toxicity will be reassessed again throughout the duration of the study.

Outcome measures

Outcome measures
Measure	Treatment (LITT, Lomustine) n=4 Participants 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. Laser Interstitial Thermal Therapy: Undergo LITT Lomustine: Given PO
Number of Participants With Incidence of Toxicity (Significant Hemorrhage or Brain Herniation) Documented on Imaging	0 Participants

SECONDARY outcome

Timeframe: approximately 3 years 3 months

Overall Survival (OS) is the time from initial tumor diagnosis (definitive surgical resection or biopsy) to death from any cause. 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.

Outcome measures

Outcome measures
Measure	Treatment (LITT, Lomustine) n=4 Participants 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. Laser Interstitial Thermal Therapy: Undergo LITT Lomustine: Given PO
Overall Survival (OS)	69 weeks Interval 9.0 to 164.0

SECONDARY outcome

Timeframe: approximately 3 years 3 months

The length of hospital stay in days, weeks or months. Length of Hospital stay was summarized by using standard descriptive statistics, such as mean, standard deviation, median, and range for continuous variables, frequency and proportion for categorical variables.

Outcome measures

Outcome measures
Measure	Treatment (LITT, Lomustine) n=4 Participants 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. Laser Interstitial Thermal Therapy: Undergo LITT Lomustine: Given PO
Length of Hospital Stay Following LITT	3 days Interval 3.0 to 4.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 4 years

Population: Data were not collected.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 4 years

Population: Data were not collected.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (LITT, Lomustine)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (LITT, Lomustine) n=4 participants at risk 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. Laser Interstitial Thermal Therapy: Undergo LITT Lomustine: Given PO
Nervous system disorders Muscle weakness right sided	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Nervous system disorders Paaresthesia (right arm numbnes)	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Nervous system disorders Headache	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Nervous system disorders Dysphasia (aphasia)	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Renal and urinary disorders Renal calculi	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.

Other adverse events

Other adverse events
Measure	Treatment (LITT, Lomustine) n=4 participants at risk 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. Laser Interstitial Thermal Therapy: Undergo LITT Lomustine: Given PO
Gastrointestinal disorders Abdominal Pain	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Psychiatric disorders Anxiety	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Gastrointestinal disorders Constipation	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Gastrointestinal disorders Dysphagia	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Nervous system disorders Dysphasia	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
General disorders Edema limbs	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Nervous system disorders Facial muscle weakness	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
General disorders Fatigue	50.0% 2/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
General disorders Gait disturbance	50.0% 2/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Nervous system disorders Headache	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
General disorders Localized edema	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Investigations Lymphocyte count decreased	50.0% 2/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Nervous system disorders Muscle weakness right-sided	50.0% 2/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Nervous system disorders Paresthesia	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.
Investigations Platelet count decreased	25.0% 1/4 • from the start of treatment through 30 days after the last dose of treatment, approximately 3 years 3 months.

Additional Information

Dr. Barbara O'Brien, MD/Associate Professor, Neuro-Oncology

UT MD Anderson Cancer Center

Phone: (713) 794-4380

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place