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Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma

Primary Purpose

Glioblastoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Radiation Therapy
Temozolomide Oral Product
Sponsored by
John Flickinger
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Chemo-Radiation Therapy, temozolomide, lymphocytopenia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria for study enrollment:

  • Age ≥18 with ability to provide written informed consent
  • Pathologically confirmed WHO Grade IV Gliobastoma prior receiving radiotherapy
  • Prior radiotherapy to a dose of ≥50Gy
  • No signs of distant metastases
  • Baseline laboratory assessment including CBC and blood chemistry, ANC > or equal 1500, Platelet count greater or equal 100. Liver function tests and creatinine not greater than twice ULN.
  • Patient should not be pregnant. Urine or blood β-HCG within 14 days prior to study start for females who are not atleast one year post-menopausal or who have ot undergone a surgical sterilization procedure
  • A baseline MRI scan of the brain is required to determine how much tumor is present for properly planning patient's radiotherapy.
  • Karnofsky Performance Status (KPS) below 60 or ECOG of 3 or 4
  • Any number or type of prior chemotherapy is allowed (patient may receive concurrent or adjuvant systemic therapy such as cetuximab at the discretion of the treating oncologic team).

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not eligible for enrollment:

  • Evidence of distant metastases on any staging or imaging modality
  • Women who are breast feeding, or have a positive pregnancy test (reproductive age should use effective birth control during study)
  • Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the principal investigator.
  • Karnofsky Performance Status less than 50
  • Prior radiotherapy to involved site in brain.

Sites / Locations

  • University of Pittsburgh Medical Center, Radiation OncologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

40 Gy in 15 fractions

25 Gy in 5 fractions

Arm Description

Patients randomized to 40 Gy in 15 fractions will receive 75 mg/m^2 temozolomide per day for 15 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year.

Patients randomized to 25 Gy in 5 fractions will receive 150 mg/m^2 temozolomide per day for 5 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year.

Outcomes

Primary Outcome Measures

Overall survival (OS)
The length of time from the start of treatment that patients remain alive.
Change in Absolute Lymphocyte Count
Differences in absolute lymphocyte count (total lymphocyte count <800 - 500/mm^3 <0.8 - 0.5 x 10^9 /L) / total # patients, during treatment.

Secondary Outcome Measures

Progression free survival (PFS) - 25 Gy in 5 fractions
The length of time during and after the treatment that a patient lives without worsening disease per Response Assessment in Neuro-Oncology (RANO) criteria. Disease progression per RANO: (any of the following): ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids*; significant increase in T2/FLAIR nonenhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor (eg, seizures, medication adverse effects) or changes in corticosteroid dose; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease.
Progression free survival (PFS) - 40 Gy in 15 fractions
The length of time during and after the treatment that a patient lives without worsening disease per Response Assessment in Neuro-Oncology (RANO) criteria. Disease progression per RANO: (any of the following): ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids*; significant increase in T2/FLAIR nonenhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor (eg, seizures, medication adverse effects) or changes in corticosteroid dose; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease.

Full Information

First Posted
July 11, 2019
Last Updated
June 16, 2023
Sponsor
John Flickinger
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1. Study Identification

Unique Protocol Identification Number
NCT04019262
Brief Title
Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma
Official Title
Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma: Comparison of Two Established Schedules
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 14, 2021 (Actual)
Primary Completion Date
December 2028 (Anticipated)
Study Completion Date
June 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
John Flickinger

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a prospective, randomized, open-label, exploratory trial of temozolomide-based chemo-radiotherapy which compares two widely used established radiation schedules with either 40 Gy in 15 fractions or 25 Gy in 5 fractions with concurrent temozolomide for both schedules in patients with glioblastoma.
Detailed Description
All patients in the study will receive usual care with short-course radiotherapy (RT) and TMZ-chemo pills. There are three phases of treatment in this study: the Chemo-radiation Phase, the Adjuvant Phase, and the Follow-Up Phase. Twenty-eight or fewer days prior to starting the Chemo-radiation Phase, patients will have a baseline Magnetic Resonance Imaging (MRI) scan. Chemo-radiation Phase: In this, patient will be assigned to either a one week or a three week treatment group with radiation treatments given approximately 5 days a week as directed by the study doctor. During this time they will also take TMZ-chemo orally (by mouth) once a day on every evening including weekends starting the evening of the day that you start radiotherapy. Once radiation is completed, you will stop taking TMZ-chemo for approximately 4 weeks before going to the next phase. Radiation therapy: Patients will be randomized between standard radiation treatment at UPMC Radiation Oncology facilities included in this protocol with either 40 Gy in 15 fractions or 25 Gy in 5 fractions, using 6 to 23 MV x-rays along with concurrent temozolomide chemotherapy for both treatment schedules. Clinical treatment volumes (CTV) will include all contrast enhancing tumor plus 1.7cm expansion into brain tissue (not crossing the tentorium) and all T2 FLAIR hyperintensity plus 7mm expansion into brain tissue (not crossing the tentorium). A planning target volume (PTV) expansion of 3mm will be then added to the CTV. No additional exclusion of brainstem or optic nerves is required as both treatment schedules are within tolerance. Treatment may be delivered with either 3D-conformal or intensity modulated radiotherapy (IMRT) techniques. Adjuvant Phase: In the Adjuvant Phase, you will receive standard monthly 5 day cycles of TMZ-chemo at 150 mg/m^2 per day for up to 1 year. Chemotherapy: Patient will receive concurrent temozolomide throughout radiation therapy, followed by standard monthly 5 day cycles for up to 1 year. Patients randomized to 25 Gy in 5 fractions will receive 150 mg/m^2 of temozolomide per day for 5 days starting first day of radiotherapy. Patients randomized to 40 Gy in 15 fractions will receive 75 mg/m2 of temozolomide per day for 19 days starting first day of radiotherapy. Patients will be appropriately pre-medicated with anti-nausea medication, prior to taking temozolomide. All patients will also receive prophylactic treatment for pneumocystis pneumonia with Bactrim or other alternative antibiotics if allergic. Follow-up Interval: Procedures performed to evaluate the safety and effectiveness of the study procedures are called "monitoring" or "follow-up" procedures. Subject participants will not be scheduled for any additional follow-up visits for this study than they would normally have if they were not in this study. Radiation Oncologists and Neuro-Oncologists usually see their patients one month after the first chemo-radiotherapy cycle before starting the next cycle of chemotherapy. After that Neuro-Oncologists and Radiation Oncologists will see the patients every 1-3 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
Chemo-Radiation Therapy, temozolomide, lymphocytopenia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
40 Gy in 15 fractions
Arm Type
Active Comparator
Arm Description
Patients randomized to 40 Gy in 15 fractions will receive 75 mg/m^2 temozolomide per day for 15 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year.
Arm Title
25 Gy in 5 fractions
Arm Type
Active Comparator
Arm Description
Patients randomized to 25 Gy in 5 fractions will receive 150 mg/m^2 temozolomide per day for 5 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year.
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Intervention Description
Radiation
Intervention Type
Drug
Intervention Name(s)
Temozolomide Oral Product
Intervention Description
Oral Temozolomide (150mg/m^2 or 75 mg/m^2)
Primary Outcome Measure Information:
Title
Overall survival (OS)
Description
The length of time from the start of treatment that patients remain alive.
Time Frame
Up to 9 years
Title
Change in Absolute Lymphocyte Count
Description
Differences in absolute lymphocyte count (total lymphocyte count <800 - 500/mm^3 <0.8 - 0.5 x 10^9 /L) / total # patients, during treatment.
Time Frame
From baseline up to 5 years.
Secondary Outcome Measure Information:
Title
Progression free survival (PFS) - 25 Gy in 5 fractions
Description
The length of time during and after the treatment that a patient lives without worsening disease per Response Assessment in Neuro-Oncology (RANO) criteria. Disease progression per RANO: (any of the following): ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids*; significant increase in T2/FLAIR nonenhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor (eg, seizures, medication adverse effects) or changes in corticosteroid dose; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease.
Time Frame
Up to 9 years
Title
Progression free survival (PFS) - 40 Gy in 15 fractions
Description
The length of time during and after the treatment that a patient lives without worsening disease per Response Assessment in Neuro-Oncology (RANO) criteria. Disease progression per RANO: (any of the following): ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids*; significant increase in T2/FLAIR nonenhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor (eg, seizures, medication adverse effects) or changes in corticosteroid dose; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease.
Time Frame
Up to 9 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Each patient must meet all of the following inclusion criteria for study enrollment: Age ≥18 with ability to provide written informed consent Pathologically confirmed WHO Grade IV Gliobastoma prior receiving radiotherapy Prior radiotherapy to a dose of ≥50Gy No signs of distant metastases Baseline laboratory assessment including CBC and blood chemistry, ANC > or equal 1500, Platelet count greater or equal 100. Liver function tests and creatinine not greater than twice ULN. Patient should not be pregnant. Urine or blood β-HCG within 14 days prior to study start for females who are not atleast one year post-menopausal or who have ot undergone a surgical sterilization procedure A baseline MRI scan of the brain is required to determine how much tumor is present for properly planning patient's radiotherapy. Karnofsky Performance Status (KPS) below 60 or ECOG of 3 or 4 Any number or type of prior chemotherapy is allowed (patient may receive concurrent or adjuvant systemic therapy such as cetuximab at the discretion of the treating oncologic team). Exclusion Criteria: Patients meeting any of the following exclusion criteria are not eligible for enrollment: Evidence of distant metastases on any staging or imaging modality Women who are breast feeding, or have a positive pregnancy test (reproductive age should use effective birth control during study) Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the principal investigator. Karnofsky Performance Status less than 50 Prior radiotherapy to involved site in brain.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Flickinger, MD
Phone
412 623 6720
Email
flickingerjc@upmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Flickinger, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh Medical Center, Radiation Oncology
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Samantha Demko, RN, BSN
Phone
412-623-1400
Email
albesl@upmc.edu
First Name & Middle Initial & Last Name & Degree
Brieana Marino, MS
Phone
412-647-8258
Email
rowlesbm@upmc.edu
First Name & Middle Initial & Last Name & Degree
John Flickinger, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma

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