Trial Outcomes & Findings for Glioblastoma Multiforme (GBM) Proton vs. Intensity Modulated Radiotherapy (IMRT) (NCT NCT01854554)

Last Updated: 2024-01-02

Results Overview

Time to cognitive failure on any of 6 primary variables from pre-specified cognitive tests (HVLT-R total recall, HVLT-R delayed recall, HVLT-R delayed recognition, TMT Part A or Part B, COWA) with failure defined as a decline that meets or exceeds the reliable change index (RCI) for each cognitive test variable. A cumulative incidence approach used to estimate median time to cognitive failure in order to account for the competing risks of disease progression and death.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

baseline, 4 months, then every 2 months for 2 years

Results posted on

2024-01-02

Participant Flow

Recruitment Details: May 2013- March 2016. All participants recruited at UT MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure	Intensity Modulated Proton Radiotherapy (IMPT) IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.	Intensity Modulated Radiotherapy (IMRT) IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMRT: IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.
Overall Study STARTED	42	48
Overall Study COMPLETED	28	39
Overall Study NOT COMPLETED	14	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Intensity Modulated Proton Radiotherapy (IMPT) IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.	Intensity Modulated Radiotherapy (IMRT) IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMRT: IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.
Overall Study Denial of Insurance Coverage	12	0
Overall Study Decided to get treatment locally	1	5
Overall Study Received IMR only due to insurance analysis	1	0
Overall Study Did Not Meet Eligibility Criteria	0	2
Overall Study Progression	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Glioblastoma Multiforme (GBM) Proton vs. Intensity Modulated Radiotherapy (IMRT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intensity Modulated Proton Radiotherapy (IMPT) n=28 Participants IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMPT: IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.	Intensity Modulated Radiotherapy (IMRT) n=39 Participants IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMRT: IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.	Total n=67 Participants Total of all reporting groups
Age, Continuous	53 years n=5 Participants	55 years n=7 Participants	53.8 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	19 Participants n=7 Participants	31 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	20 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized White	26 Participants n=5 Participants	31 Participants n=7 Participants	57 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants	39 participants n=7 Participants	67 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 4 months, then every 2 months for 2 years

Outcome measures

Outcome measures
Measure	Intensity Modulated Radiotherapy (IMRT) n=35 Participants IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMRT: IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.	Intensity Modulated Proton Radiotherapy (IMPT) n=24 Participants IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMPT: IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.
Time to Cognitive Failure	7.7 months Interval 4.2 to Not estimable	4.9 months Interval 3.3 to Not estimable

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Population: Between June 2013 and March 2016, 90 participants consented to participate and 67 (41 and 26 participants effectively treated with IMRT and IMPT) were treated with the majority of participants excluded before treatment began due to insurance denial of proton therapy.

Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Intensity Modulated Radiotherapy (IMRT) n=41 Participants IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMRT: IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.	Intensity Modulated Proton Radiotherapy (IMPT) n=26 Participants IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMPT: IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.
Overall Survival	21.2 months Interval 16.4 to 33.7	24.5 months Interval 17.3 to 34.8

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

Population: Between June 2013 and March 2016, 90 patients consented to participate and 67 (41 and 26 participants effectively treated with IMRT and IMPT) were treated with the majority of participants excluded before treatment began due to insurance denial of proton therapy.

Measured from date of registration to date of first observation of progressive disease, symptomatic deterioration or death due to any cause. Participants last known to be alive and progression-free are censored at date of last contact.

Outcome measures

Outcome measures
Measure	Intensity Modulated Radiotherapy (IMRT) n=41 Participants IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMRT: IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.	Intensity Modulated Proton Radiotherapy (IMPT) n=26 Participants IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMPT: IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.
Progression Free Survival (PFS)	8.9 months Interval 7.6 to 13.6	6.6 months Interval 3.9 to 14.3

SECONDARY outcome

Timeframe: 2 years

The adverse severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0). Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4 Life-threatening consequences; urgent intervention indicated. Count of participants experiencing adverse events. Should a participant experience multiple adverse events at different grades, the patient is counted only once at the highest grade.

Outcome measures

Outcome measures
Measure	Intensity Modulated Radiotherapy (IMRT) n=41 Participants IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMRT: IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.	Intensity Modulated Proton Radiotherapy (IMPT) n=26 Participants IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMPT: IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.
Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher) Grade 4 Adverse Events	2 Participants	1 Participants
Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher) Grade 3 Adverse Events	4 Participants	2 Participants
Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher) Grade 2 Adverse Events	14 Participants	5 Participants

Adverse Events

Intensity Modulated Radiotherapy (IMRT)

Serious events: 2 serious events

Other events: 29 other events

Deaths: 29 deaths

Intensity Modulated Proton Radiotherapy (IMPT)

Serious events: 1 serious events

Other events: 19 other events

Deaths: 22 deaths

Serious adverse events

Serious adverse events
Measure	Intensity Modulated Radiotherapy (IMRT) n=41 participants at risk IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMRT: IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.	Intensity Modulated Proton Radiotherapy (IMPT) n=26 participants at risk IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. IMPT: IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments. Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years. Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.
Blood and lymphatic system disorders Platelet count decreased	4.9% 2/41 • 2 years During this study, both the Intensity Modulated Radiotherapy (IMRT) and Intensity Modulated Proton Radiotherapy (IMPT) arms reported serious and life-threatening adverse events. Specifically, 2 participants in the IMRT arm and 1 participant in the IMPT arm experienced Grade 4 life-threatening events that required urgent intervention	3.8% 1/26 • 2 years During this study, both the Intensity Modulated Radiotherapy (IMRT) and Intensity Modulated Proton Radiotherapy (IMPT) arms reported serious and life-threatening adverse events. Specifically, 2 participants in the IMRT arm and 1 participant in the IMPT arm experienced Grade 4 life-threatening events that required urgent intervention

Other adverse events

Additional Information

Dr. Caroline Chung, MD- VP, Chief Data Officer, Data Impact & Governance

UT MD Anderson Cancer Center

Phone: (713) 745-5422

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place