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

NCT03022578 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: 2016-0443NCI-2018-01286P30CA016672
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

IDH Family Wildtype; Recurrent Anaplastic Astrocytoma; Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate at 6 Months

  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.

  At 6 months

Secondary Outcomes (6)

• Time to Progression (TTP)

  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

• Long-term Steroid Requirements

  Up to 4 years

• MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Data

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

• Number of Participants With Incidence of Toxicity (Significant Hemorrhage or Brain Herniation) Documented on Imaging

  approximately 3 years 3 months

• Overall Survival (OS)

  approximately 3 years 3 months

Other Outcomes (2)

• Biomarkers in Peripheral Blood and Tumor Tissue

  Up to 4 years

• Inflammatory/Immunologic Profile

  Up to 4 years

Study Arms (1)

Treatment (LITT, lomustine)

EXPERIMENTAL

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; Drug: Lomustine

Interventions

Laser Interstitial Thermal Therapy PROCEDURE

Undergo LITT

Also known as: LITT

Treatment (LITT, lomustine)

Lomustine DRUG

Given PO

Also known as: 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

Treatment (LITT, lomustine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) (performed 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Astrocytoma; Glioblastoma

Interventions

Lomustine

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Results Point of Contact

• Title: Dr. Barbara O'Brien, MD/Associate Professor, Neuro-Oncology
• Organization: UT MD Anderson Cancer Center

bjobrien@mdanderson.org

(713) 794-4380

Study Officials

• Barbara J O'Brien

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2017
• First Posted: January 16, 2017
• Study Start: November 7, 2017
• Primary Completion: February 16, 2021
• Study Completion: February 16, 2021
• Last Updated: August 10, 2022
• Results First Posted: August 10, 2022

Record last verified: 2022-07

Locations

US (1)