Phase 1-2 of Temozolomide and Hypofractionated Radiotherapy in Tx of Supratentorial Glioblastoma Multiform

NCT01120639 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB-17774SU-04202010-5726BRN0012
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the safety and effectiveness of a combination treatment for glioblastoma multiforme utilizing radiotherapy plus the FDA-approved chemotherapy drug temozolomide

Conditions

Glioblastoma; Cancer of Brain and Nervous System; Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• Number of Dose-limiting Toxicities (DLTs)

  The maximum-tolerated dose (MTD) of study treatment (temozolomid plus hypofractionated radiotherapy administered as 5 fractions) is defined as either: * The highest radiation dose per protocol, or * The radiation dose at which dose-limiting toxicities (DLTs) occurred in ≥ 2 of 3 participants at a dose level, and/or ≥ 2 of 6 participants, at a dose level. Dose-limiting toxicity (DLT) was defined as a treatment-related (with possible, probable or definite attribution) Grade 3 to 5 CNS toxicity \[Common Terminology Criteria for Adverse Events (CTCAE) v4\] occurring within 30 days of stereotactic radiosurgery (SRS). The non-stratified outcome is reported as the number of DLTs observed in by radiation dose and by strata (Planning Target Volume (PTV) \< 60 cm³ and from 60 to 150 cm³).

  30 days

Secondary Outcomes (9)

• Number of Acute Toxicity Within 30 Days

  30 days

• Long-term Toxicity After More Than 30 Days

  12 months

• Percent of Participants With Radiographic Response

  6 months

• Progression-free Survival

  18 Months.

• Overall Survival (OS)

  20 Months.

Study Arms (4)

Stereotactic Radiosurgery (25 Gray x 5 fractions)+Temozolomide

EXPERIMENTAL

Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

Drug: Temozolomide; Procedure: Stereotactic Radiosurgery (SRS)

Stereotactic Radiosurgery (30 Gray x 5 fractions)+Temozolomide

EXPERIMENTAL

Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

Drug: Temozolomide; Procedure: Stereotactic Radiosurgery (SRS)

Stereotactic Radiosurgery (35 Gray x 5 fractions)+Temozolomide

EXPERIMENTAL

Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

Drug: Temozolomide; Procedure: Stereotactic Radiosurgery (SRS)

Stereotactic Radiosurgery (40 Gray x 5 fractions)+Temozolomide

EXPERIMENTAL

Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

Drug: Temozolomide; Procedure: Stereotactic Radiosurgery (SRS)

Interventions

Temozolomide DRUG

75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy.

Also known as: Temodar, Temodal

Stereotactic Radiosurgery (25 Gray x 5 fractions)+Temozolomide; Stereotactic Radiosurgery (30 Gray x 5 fractions)+Temozolomide; Stereotactic Radiosurgery (35 Gray x 5 fractions)+Temozolomide; Stereotactic Radiosurgery (40 Gray x 5 fractions)+Temozolomide

Stereotactic Radiosurgery (SRS) PROCEDURE

Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)

Also known as: Hypofractionated stereotactic radiosurgery (h-SRS), Hypofractionated stereotactic radiotherapy, Cyberknife surgery

Stereotactic Radiosurgery (25 Gray x 5 fractions)+Temozolomide; Stereotactic Radiosurgery (30 Gray x 5 fractions)+Temozolomide; Stereotactic Radiosurgery (35 Gray x 5 fractions)+Temozolomide; Stereotactic Radiosurgery (40 Gray x 5 fractions)+Temozolomide

Eligibility Criteria

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

You may qualify if:

• Histopathologically confirmed newly diagnosed glioblastoma multiforme. Diagnosis must be made by surgical biopsy or excision
• The tumor must be supratentorial in location
• The planning target volume (tumor plus margin) must measure ≤ 150 cm\^3 in volume
• Age ≥ 18 years
• Life expectancy of at least 12 weeks
• Patient must have adequate organ function to tolerate temozolomide (details in the protocol)

You may not qualify if:

• Patients who have previously been treated with brain irradiation to the region that would result in overlap of the radiation fields
• Tumor foci detected below the tentorium
• Multifocal disease or leptomeningeal spread
• Prior allergic reaction to the study drugs involved in this protocol
• Patients with pacemaker will be allowed to undergo CT instead of MRI
• Pediatric patients (age \< 18), pregnant women, and nursing patients will be excluded

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Neurologic Manifestations

Interventions

Temozolomide; Radiosurgery

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Scott Soltys (Associate Professor of Radiation Oncology)
• Organization: Stanford University

sgsoltys@stanford.edu

650-724-1569

Study Officials

• Scott Gerard Soltys, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Radiation Oncology

Model Details: Dose-escalation with 2-level stratification

Study Record Dates

• First Submitted: May 7, 2010
• First Posted: May 11, 2010
• Study Start: April 1, 2010
• Primary Completion: November 1, 2016
• Study Completion: November 15, 2020
• Last Updated: August 6, 2021
• Results First Posted: July 31, 2019

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)