Sulfasalazine and Stereotactic Radiosurgery for Recurrent Glioblastoma (SAS-GKRS)

March 2, 2023 updated by: Haukeland University Hospital

Phase I Trial Combining Sulfasalazine and Gamma Knife Radiosurgery for Recurrent Glioblastoma

This study evaluates the safety associated with the addition of sulfasalazine to stereotactic radiosurgery for recurrent glioblastoma. Sulfasalazine is a potential tumor selective radiosensitizer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Glioblastoma is the most aggressive and most common type of primary brain cancer. Standard treatment at diagnosis is surgery followed by high dose radiation therapy and chemotherapy. Despite initial treatment nearly all patients will experience recurrence of the tumor with a dismal prognosis. There is no consensus on standard of care at recurrence. Reoperation is associated with a high risk of complications and further conventional radiation therapy is often not possible as the maximum tolerated dose to the normal brain has already been given. In addition most tumors have developed resistance towards chemotherapy. Stereotactic radiosurgery (SRS) may be administered despite prior initial radiation treatment but in order to avoid radiation induced complications only limited doses to limited tumor volumes can be applied.

Developing new strategies to improve the effect of radiation selectively on tumor cells without simultaneously increase the radiation induced damage of normal brain would be valuable.

The investigators have shown in experimental studies that the drug sulfasalazine enhances the number of cancer cells that dies as result of radiation therapy and thereby improves survival in combination with SRS in animals with glioblastoma. Sulfasalazine inhibits the production of an antioxidant that normally protects the tumor against radiation. Hopefully the trial will result in a new and more effective treatment option for patients with recurrent glioblastoma.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Bergen, Norway, 5021
        • Haukeland University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Histologically verified glioblastoma multiforme with recurrence (first or second relapse, all subtypes) based on the Response Assessment in Neuro-Oncology criteria.
  • Prior standard therapy for newly diagnosed glioblastoma consisting of surgery, standard fractionated radiotherapy to 60 Gy concomitant with Temozolomide
  • Has been informed of other treatment options
  • Must be eligible to gamma knife treatment
  • Tumor size ≤ 3 cm in diameter (≤ 15 cm3 ) on MRI dated no more than 30 days before SRS treatment
  • Must be at least 18 years of age
  • Must be ambulatory with a Karnofsky performance status of ≥ 70
  • Life expectancy > 12 weeks
  • Laboratory parameters for vital functions should be in the normal reference range. Laboratory abnormalities that are not clinically significant are generally permitted, except for the following laboratory parameters, which must be within the ranges specified:

Hematology: White blood cell count: ≥ 3.0 x 109/l, Platelet count:: ≥ 100 x 109/l, Hemoglobin: ≥ 100 g/l, Total bilirubin level: <1.5 times the upper limit of normal (ULN) (except in patients with Gilbert's Syndrome who must have a total bilirubin less than 51,3 µmol/L), alanine aminotransferase < 3 times the ULN, Creatinine < 1.5 times the ULN, Normal prothrombin time / international normalized ratio (PT INR) < 1.4, Absolute neutrophil count: ≥ 1 x109/L without the support of filgrastim.

  • More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria.
  • Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to national/local regulations

Exclusion Criteria:

  • Allergy to sulfa drugs
  • Adverse reactions to salicylates
  • Known hypersensitivity to sulfasalazine, its metabolites or any of the excipients (Povidone; Maize starch; magnesium stearate; colloidal silicon dioxide)
  • Eligible to alternative standard treatments with temozolomide
  • Treatment with sulfasalazine after glioblastoma diagnosis
  • Participation in pharmacokinetic trial within 4 weeks
  • Participation in immunotherapy trial within 4 weeks
  • History of psychological symptoms affecting ability to consent to and/or fulfill the protocol
  • Other malignant diseases and multiple sclerosis
  • Pregnant or breast feeding patients.
  • Porphyria
  • Kidney of liver deficiencies
  • Glucose-6-phosphate dehydrogenase deficiency
  • Severe allergy or bronchial asthma
  • History of erythema multiforme
  • Significant heart failure or renal failure
  • Intestinal or urinary obstruction
  • Any reason why, in the opinion of the investigator, the patient should not participate (e.g. not able to comply with study procedures).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Sulfasalazine in addition to stereotactic radiosurgery

3 + 3 dose escalation The first cohort of 3-6 patients will receive 1.5 g Sulfasalazine daily for 3 days before single fraction stereotactic radiosurgery utilizing 12 Gy prescription dose to the tumor margin.

The second, third and fourth cohort will receive 3 days pretreatment with 3 g, 4.5 g and 6 g Sulfasalazine, respectively, before 12 Gy single fraction stereotactic radiosurgery.
Drug: Sulfasalazine
Sulfasalazine combined with stereotactic radiosurgery
Other Names:
  • Stereotactic radiosurgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity (Common Terminology Criteria for Adverse Event v 4.0)
Time Frame: 1 month
Determining the maximum tolerated and recommended dose of sulfasalazine as radiosensitizer.
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intratumoral Glutathione production
Time Frame: 4 days
Monitor the effect of sulfasalazine on the level of Glutathione production in glioma cells.
4 days
Presence of radiation necrosis
Time Frame: 1 month
Monitor late toxicity of sulfasalazine combined with stereotactic radiosurgery on Positron Emission Tomography.
1 month
Progression free survival
Time Frame: 1 year
Monitor the preliminary effect of sulfasalazine combined with stereotactic radiosurgery on local tumor control.
1 year
Overall survival
Time Frame: 2 years
Assess the preliminary efficacy of sulfasalazine in combination with SRS on survival.
2 years
Quality of life (Functional Assessment of Cancer Therapy-Brain)
Time Frame: 1 year
Assess the preliminary efficacy of sulfasalazine in combination with SRS on changes in quality of life utilizing the brain cancer subscale of the functional assessment of cancer therapy-Brain (FACT-Br) questionaire. The brain cancer subscale consists of twenty-three items regarding neurological concerns (range: 0-76 points). The response to the items uses a five-point scale ranging from 0 (not at all) to 4 (very much). The higher the patient score, the better the quality of life.
1 year
Karnofsky performance score (KPS)
Time Frame: 1 year
Assess the preliminary efficacy of sulfasalazine in combination with stereotactic radiosurgery on changes in the Karnofsky performance score (range 0 - 100 points). The higher the score, the better is the functional performance status of the patient.
1 year
Steroid use in mg over time
Time Frame: 1 year
Assess the preliminary efficacy of sulfasalazine in combination with stereotactic radiosurgery on the patients´ need for steroid medication. The change in steroid use in mg from baseline up to 1 year following radiosurgery will be evaluated using descriptive statistics.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Haukeland University Hospital

Collaborators

Northwell Health
University of Bergen
Weill Medical College of Cornell University
Helse Stavanger HF
Norwegian Cancer Society

Investigators

  • Principal Investigator: Bente S Skeie, Haukeland University Hospial

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2020

Primary Completion (Actual)

October 14, 2022

Study Completion (Actual)

October 14, 2022

Study Registration Dates

First Submitted

November 21, 2019

First Submitted That Met QC Criteria

December 18, 2019

First Posted (Actual)

December 19, 2019

Study Record Updates

Last Update Posted (Actual)

March 3, 2023

Last Update Submitted That Met QC Criteria

March 2, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019/6834

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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