Trial Outcomes & Findings for Mathematical Model-Adapted Radiation In Glioblastoma (NCT NCT03557372)

Results Overview

Successful completion of radiotherapy is defined as receipt of all scheduled fractions of daily radiotherapy within 24 hours of once daily fractions and within 1 hour of three-times daily fractions.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

14 participants

Primary outcome timeframe

10 Days

Results posted on

2023-10-26

Participant Flow

There are no details to report.

Participant milestones

Participant milestones
Measure	Mathematical Model-Adapted Radiation Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Mathematical Model-Adapted Radiation In Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mathematical Model-Adapted Radiation n=14 Participants Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=93 Participants
Age, Categorical >=65 years	1 Participants n=93 Participants
Sex: Female, Male Female	4 Participants n=93 Participants
Sex: Female, Male Male	10 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	14 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	14 participants n=93 Participants

PRIMARY outcome

Timeframe: 10 Days

Population: All 14 participants were analyzed for the primary endpoint.

Successful completion of radiotherapy is defined as receipt of all scheduled fractions of daily radiotherapy within 24 hours of once daily fractions and within 1 hour of three-times daily fractions.

Outcome measures

Outcome measures
Measure	Mathematical Model-Adapted Radiation n=14 Participants Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Number of Participants to Complete Model Adapted Radiations Fractionation Scheduled	14 Participants

SECONDARY outcome

Timeframe: 6 months

Radiation necrosis (RN) was defined by clinical assessment including imaging features of an expansile, centrally hypointense lesion with increasing surrounding vasogenic edema and typically without features of high grade recurrence (restricted diffusion, elevated cerebral blood volume). Symptomatic RN included patients with radiographic RN requiring intervention such as corticosteroid therapy for neurologic symptoms, headaches, or signs of elevated intracranial pressure.

Outcome measures

Outcome measures
Measure	Mathematical Model-Adapted Radiation n=14 Participants Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Number of Participants With Radiation Necrosis	0 Participants

SECONDARY outcome

Timeframe: 6 months

Count of number of patients developing new/worsening seizures within 6 months of receiving protocol radiation therapy

Outcome measures

Outcome measures
Measure	Mathematical Model-Adapted Radiation n=14 Participants Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Number of Participants With Seizures	1 Participants

SECONDARY outcome

Timeframe: range of follow-up from date of registration was 1.2 - 38.6 months

Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Outcome measures

Outcome measures
Measure	Mathematical Model-Adapted Radiation n=14 Participants Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Overall Survival (OS)	7.3 Months Interval 4.7 to 10.7

SECONDARY outcome

Timeframe: 6 Months

All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3-5 AE of any type during the time of observation.

Outcome measures

Outcome measures
Measure	Mathematical Model-Adapted Radiation n=14 Participants Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Grade 3-5 Treatment-related Toxicity Rate	0.29 proportion of treated participants

SECONDARY outcome

Timeframe: Disease evaluated on visit 4,5,6 and every 2-4 months in long-term. The range of follow-up from date of registration was 1.2 - 38.6 months and the median was 7.3 months.

Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) (defined protocol section 12.7) or death, or is censored at time of last disease assessment.

Outcome measures

Outcome measures
Measure	Mathematical Model-Adapted Radiation n=14 Participants Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Median Progression-Free Survival (PFS)	4.3 Months Interval 2.4 to 5.2

SECONDARY outcome

Timeframe: Disease evaluated on visit 4,5,6 and every 2-4 months in long-term. The range of follow-up from date of registration was 1.2 - 38.6 months and the median was 7.3 months.

Local recurrence-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented Local recurrence or death, or is censored at time of last disease assessment.

Outcome measures

Outcome measures
Measure	Mathematical Model-Adapted Radiation n=14 Participants Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Median Local Recurrence-free Survival	6.2 Months Interval 5.2 to 30.0

SECONDARY outcome

Timeframe: 6 Months

Count of patients undergoing salvage craniotomy for resection or decompression of progressively enlarging tumor within 6 months of receipt of protocol radiation therapy.

Outcome measures

Outcome measures
Measure	Mathematical Model-Adapted Radiation n=14 Participants Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Number of Participants Undergoing Salvage Craniotomy	0 Participants

SECONDARY outcome

Timeframe: 6 Months

Count of patients undergoing systemic therapies for presumed recurrence or progression of disease within 6 months after receipt of protocol radiation therapy

Outcome measures

Outcome measures
Measure	Mathematical Model-Adapted Radiation n=14 Participants Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Number of Participants Receiving Additional Systemic Treatments After Reirradiation	3 Participants

Adverse Events

Mathematical Model-Adapted Radiation

Serious events: 8 serious events

Other events: 8 other events

Deaths: 13 deaths

Serious adverse events

Serious adverse events
Measure	Mathematical Model-Adapted Radiation n=14 participants at risk Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
General disorders Death NOS	57.1% 8/14 • Number of events 8 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Seizure	7.1% 1/14 • Number of events 1 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Edema cerebral	7.1% 1/14 • Number of events 1 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Hydrocephalus	7.1% 1/14 • Number of events 1 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.

Other adverse events

Other adverse events
Measure	Mathematical Model-Adapted Radiation n=14 participants at risk Mathematical Model-Adapted Radiation Fractionation Schedule Mathematical Model-Adapted Radiation Fractionation Schedule: - Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Gastrointestinal disorders Nausea	7.1% 1/14 • Number of events 1 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	14.3% 2/14 • Number of events 2 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Infections and infestations Infections and infestations - Other, specify	7.1% 1/14 • Number of events 1 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.1% 1/14 • Number of events 1 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	7.1% 1/14 • Number of events 1 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Ataxia	7.1% 1/14 • Number of events 1 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Edema cerebral	7.1% 1/14 • Number of events 1 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Headache	7.1% 1/14 • Number of events 1 • Time-frame for observation of adverse events was up to 6 months of clinical follow up, and for all cause-mortality, up to 38.6 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv5. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.

Additional Information

Dr. Shyam Tanguturi

Dana Farber Cancer Institute

Phone: 617-632-0000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place