Early Temozolomide in Patients With High-Grade Gliomas in Rehabilitation

Early Post-surgical Temozolomide Therapy in Patients With High-Grade Gliomas Admitted to Acute Rehabilitation: A Feasibility Study

The purpose of this study is to investigate the feasibility of a possible treatment regimen that could be used to delay tumor progression in patients with glioblastoma. The study is being conducted in patients who qualify for inpatient rehabilitation, as this population is particularly vulnerable to delays in initiation of chemoradiation and further tumor growth in the period between surgical resection and the start of treatment.

Study Overview

• Status: Withdrawn
• Conditions: Glioma of Brain
• Intervention / Treatment: Drug: Temozolomide

Detailed Description

This is a pilot study to evaluate the feasibility and safety of early postsurgical temozolomide therapy prior to initiation of standard chemoradiation regimen in patients with glioblastoma who undergo inpatient rehabilitation. The study will be conducted with adult patients who qualify for inpatient rehabilitation following surgical resection of pathologically confirmed Grade IV glioma. Patients will begin a 21-day cycle of temozolomide starting 14 days after surgery at 75mg per square meter of body surface area daily to serve as bridge therapy. Patients will then progress to receive standard therapy following their rehabilitation stay. Patients will be assessed for their ability to complete the chemotherapy protocol without dose-limiting toxicity as well as complete inpatient rehabilitation successfully. Additionally, we will be assessing for tumor progression between the time of surgery and the time of treatment initiation.

If this study shows the expected results, the research team plans to proceed to a larger trial assessing the efficacy of early TMZ in patients with glioblastoma (GBM) who are admitted to acute inpatient rehabilitation compared to the current standard of care.

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients, aged 18+
• Newly diagnosed World Health Organization (WHO) Grade IV glioma, confirmed on pathology
• Karnofsky Performance Score ≥ 60
• Subject has undergone biopsy, subtotal resection, or gross total resection of tumor
• Subject has been evaluated by physical therapy and thought to be a candidate for acute rehabilitation
• Subject must be accepted for admission on 5-1200 unit at Strong Memorial Hospital
• Subject must be able to provide informed consent

• Subject must meet the following laboratory parameters:

  • Absolute neutrophil count > 1.5 x103/uL
  • Platelet count > 140 x103/uL
  • Alanine transaminase < 135 U/L
  • Aspartate transaminase < 120 U/L

Exclusion Criteria:

• Subject has received previous treatment for high-grade glioma
• Subject has other active malignancy
• Subject is currently pregnant or breastfeeding
• Subject is a women of childbearing potential who is not using a reliable method of contraception
• Subject has history of hypersensitivity to temozolomide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Temozolomide Arm; This study will only include one treatment group who will receive oral temozolomide at 75 mg per square meter of body surface area daily for 21 days before progressing to standard chemoradiation treatment.	Drug: Temozolomide; oral temozolomide at 75 mg per square meter of body surface area daily for 21 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patient who fail to complete temozolomide (TMZ)	The number of subjects who fail to complete early TMZ plus inpatient rehabilitation for any reason, including adverse events or progression or patient withdrawal	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean functional independence measure (FIM) score	FIM is comprised of 18 items, grouped into 2 subscales -motor and cognition. Each item is scored on a 7 point ordinal scale, ranging from a score of 1 to a score of 7. The higher the score, the more independent the patient is in performing the task associated with that item therefore the better the health outcome. The total score for the FIM instrument (the sum of the motor and cognition subscale scores) will be a value between 18 and 126.	1 month
Response rate to TMZ	The response rate to early TMZ will be evaluated by comparing the MRI of the head before and after one course using the Response Assessment in Neuro-Oncology (RANO) criteria. The response rate will be reported with a (two-sided) 90% confidence interval. The RANO criteria consists of 5 elements: T1 Gadolinium enhancing disease, T2/FLAIR assessment, new lesions, use of corticosteroids and clinical status. Patients will be categorized as complete response, partial response, stable disease or progressive disease.	1 month

Collaborators and Investigators

• Sponsor: University of Rochester
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Kevin A Walter, MD, University of Rochester Medical Center, Dept. of Neurosurgery

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2021
• Primary Completion (Anticipated): December 15, 2021
• Study Completion (Anticipated): December 15, 2021

Study Registration Dates

• First Submitted: January 4, 2019
• First Submitted That Met QC Criteria: January 4, 2019
• First Posted (Actual): January 8, 2019

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: RSRB00003258

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No