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NCT03189381

Pilot Phase 2 Study Whole Brain Radiation Therapy With Simultaneous Integrated Boost for Patients With Brain Metastases

Terminated NA Results posted Last updated 28 June 2024
What this trial tests

NA trial testing Cohort A in Brain Metastases in 20 participants. Terminated before completion.

Timeline
21 September 2017
Primary endpoint
30 September 2022
30 September 2022

Quick facts

Lead sponsorIndiana University
PhaseNA
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment20
Start date21 September 2017
Primary completion30 September 2022
Estimated completion30 September 2022
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Indiana University

Who can join

18 and older, any sex, with Brain Metastases. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

In-Brain Distant Failure Rate Primary · 6 Months

An actuarial 6-month rate of new parenchymal lesions seen outside the planning target volume of any lesion that received SIB on any post-treatment MRI (in all 3 planes). This is the binomial proportion of patients who experienced in-brain distant failure by 6 months and the associated 95% confidence interval.

GroupValue95% CI
Cohort A0.4440.137 – 0.788
Treated Lesion Local Control Secondary · 6 Months

An actuarial 6-month rate of any new, recurrent, or progressing (as defined by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria) tumor within the planning target volume on any post-treatment MRI. This details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last know alive or at the date of death if they expired.

GroupValue95% CI
Cohort A1.0001.000 – 1.000
Overall Survival for Evaluable Patients Secondary · 6 Months

An actuarial 6-month rate of patients still alive regardless of disease status. This details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. For patients who expired, the time from treatment start to death was calculated. Patients who did not expire were censored at the date last know alive.

GroupValue95% CI
Cohort A1.0001.000 – 1.000
Change in Neurocognitive Function From Baseline to 6 Months Secondary · 6 Months

The change in scores from the neurocognitive test were calculated by subtracting the baseline score from the 6-month score. Positive values indicate an increase from baseline and negative values indicate a decrease. The neurological test scores were assessed with the Hopkins Verbal Learning Test - Revised (HVLT). In the HVLT, 12 nouns are read and the participant is asked to recall in 3 rounds. Total words recalled are summed for the Total Recall score ranging from 0-36 (higher score represents better recall). The delayed recall score is tested 20-25 mins after the initial recall and ranges f

Total Recall Raw Score
GroupValue95% CI
Cohort A-1.00-2.25 – 0.25
Delayed Recall Raw Score
GroupValue95% CI
Cohort A-1.00-2.75 – 0.25
Recognition Discrimination Index Raw Score
GroupValue95% CI
Cohort A0.00-2.75 – 0.00
Change in Health-Related Quality of Life (QoL) From Baseline to 6 Months Secondary · 6 Months

The change in scores of health-related quality of life test from baseline to 6 months calculated by subtracting the baseline score from the 6-month score. Positive values indicate an increase in score from baseline to 6 months while negative values indicate a decrease. The Functional Assessment of Cancer Therapy with Brain Subscale (FACT-Br) asks questions on a scale from 0 to 4 with 0 being "not at all" and 4 being "very much". Responses were reversed, if applicable, and compiled to calculate physical well-being (range: 0-28), social/family well-being (range: 0-28), emotional well-being (ran

Physical Well-Being
GroupValue95% CI
Cohort A-1.00-2.00 – 1.00
Social/Family Well-Being
GroupValue95% CI
Cohort A-2.00-2.00 – 1.00
Emotional Well-Being
GroupValue95% CI
Cohort A-1.00-2.00 – 0.00
Functional Well-Being
GroupValue95% CI
Cohort A-1.00-3.00 – 1.00
Bone Marrow Transplant (BMT) Subscale
GroupValue95% CI
Cohort A0.00-3.00 – 2.00
Trial Outcome Index
GroupValue95% CI
Cohort A-4.00-6.00 – 1.00
FACT-G
GroupValue95% CI
Cohort A-2.00-7.00 – 4.00
FACT-BMT
GroupValue95% CI
Cohort A-1.00-8.00 – 3.83
Change in Performance Status Secondary · 12 Months

Total change in performance status score was calculated by substracting the baseline score from the follow-up score. Positive values indicate an increase in score from baseline while negative values indicate a decrease in score from baseline. Functional status evaluated using the Karnofsky Performance Score (KPS) Index. The KPS score is evaluated on a scale from 0 to 100 where 0 is death and 100 is "normal no complaints; no evidence of disease".

Baseline to 3 Months
GroupValue95% CI
Cohort A-10.00-10.00 – 10.00
Baseline to 6 Months
GroupValue95% CI
Cohort A0.000.00 – 0.00
Baseline to 12 Months
GroupValue95% CI
Cohort A0.000.00 – 5.00
Incidence of Early and Late Treatment-Related Adverse Effects Secondary · Up To 39 Months

This is the percentage of eligible patients who experienced the respective treatment-related AE while on study. Adverse effects (AEs) were defined per CTCAE and considered treatment-related if the AE start date occurred on or after the first date of treatment and it was possibly, probably, or definitely related to treatment. AEs were recorded from the start of treatment until the patient was off-study.

Fatigue
GroupValue95% CI
Cohort A50.00
Alopecia
GroupValue95% CI
Cohort A30.00
Memory Impairment
GroupValue95% CI
Cohort A25.00
Headache
GroupValue95% CI
Cohort A10.00
Somnolence
GroupValue95% CI
Cohort A10.00
Blurred Vision
GroupValue95% CI
Cohort A5.00
Cognitive Disturbance
GroupValue95% CI
Cohort A5.00
Dermatitis Radiation
GroupValue95% CI
Cohort A5.00
Overall Survival for Eligible Patients Secondary · 6 Months

An actuarial 6-month rate of patients still alive regardless of disease status. This details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. For patients who expired, the time from treatment start to death was calculated. Patients who did not expire were censored at the date last know alive.

GroupValue95% CI
Cohort A0.7000.451 – 0.853
Change in Neurocognitive Function Retention Percentage Raw Score From Baseline to 6 Months Secondary · 6 Months

The change in scores from the neurocognitive test were calculated by subtracting the baseline score from the 6-month score. Positive values indicate an increase from baseline and negative values indicate a decrease. The neurological test scores were assessed with the Hopkins Verbal Learning Test - Revised (HVLT). In the HVLT, 12 nouns are read and the participant is asked to recall in 3 rounds. Total words recalled are summed for the Total Recall score ranging from 0-36 (higher score represents better recall). The delayed recall score is tested 20-25 mins after the initial recall and ranges f

GroupValue95% CI
Cohort A-3.00-30.50 – 2.25

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected throughout the study and assessed up to 39 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A
Serious: 9/20 (45%)
Deaths: 15/20
Cohort B
Serious: 0
Deaths: 0

Serious adverse events (16 terms)

ReactionSystemCohort ACohort B
Abdominal painGastrointestinal disorders
Breast infectionInfections and infestations
ConfusionPsychiatric disorders
DehydrationMetabolism and nutrition disorders
DysarthriaNervous system disorders
DysphagiaGastrointestinal disorders
EncephalopathyNervous system disorders
FallInjury, poisoning and procedural complications
Gait disturbanceGeneral disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
HallucinationsPsychiatric disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Neutrophil count decreasedInvestigations
SepsisInfections and infestations
Thromboembolic eventVascular disorders
Urinary tract infectionInfections and infestations
Other adverse events (99 terms — click to expand)

ReactionSystemCohort ACohort B
FatigueGeneral disorders
HeadacheNervous system disorders
AlopeciaSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Edema limbsGeneral disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
Memory impairmentNervous system disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
Blurred visionEye disorders
ConstipationGastrointestinal disorders
DiarrheaGastrointestinal disorders
DysphagiaGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
SomnolenceNervous system disorders
Sore throatRespiratory, thoracic and mediastinal disorders
AnxietyPsychiatric disorders
DysgeusiaNervous system disorders
FallInjury, poisoning and procedural complications
Mucosal infectionInfections and infestations
Thromboembolic eventVascular disorders
ArthralgiaMusculoskeletal and connective tissue disorders
AtaxiaNervous system disorders
BruisingInjury, poisoning and procedural complications
ChillsGeneral disorders
ConfusionPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
DehydrationMetabolism and nutrition disorders
DizzinessNervous system disorders
FeverGeneral disorders
Gait disturbanceGeneral disorders
HypoglycemiaMetabolism and nutrition disorders
Infections and infestations - Other, specifyInfections and infestations
InsomniaPsychiatric disorders
LeukocytosisBlood and lymphatic system disorders
Lymphocyte count decreasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
Oral painGastrointestinal disorders

Most-reported serious reactions: Abdominal pain, Breast infection, Confusion, Dehydration, Dysarthria, Dysphagia, Encephalopathy, Fall.

Data from ClinicalTrials.gov NCT03189381 adverse events section.

Sponsor's own description

This trial is a pilot, Phase 2, sequential two-cohort study designed to test two de-escalated whole brain radiation therapy (WBRT) dose levels and assess their ability to maintain acceptable in-brain distant control. The WBRT dose would decrease as the study moves forward, both in terms of absolute value and equivalent dose in 2 Gray fractions (EQD2) (as determined by the linear quadratic radiobiological model). The absolute value of the simultaneous integrated boost (SIB) dose will change with each dose level because the number of fractions delivered will depend on the WBRT dose. As such, the SIB dose will be manipulated such that the EQD2 will remain essentially equivalent despite the difference in the number of fractions delivered. This design will ensure that the only variable is the change in WBRT dose. The concept is that WBRT with SIB would be expected to maximize both local and in-brain distant control as has already been shown in studies exploring WBRT with SRS boost. However, by itself WBRT with SIB does not address the concern over neurocognitive outcomes. Therefore, investigators hypothesize that there is a lower WBRT dose threshold that will maintain acceptable in-brain distant control, particularly in the setting of a SIB to gross lesions to maintain treated lesion control. In addition, lower overall brain dose (including lower hippocampal dose without specific hippocampal avoidance) may potentially improve neurocognitive function. Investigators are also interested in evaluating treated lesion control, overall survival, neurocognitive sequelae of therapy, quality of life, performance status, and adverse effects of therapy. Biomarker identification for potential correlative circulating tumor DNA and microRNA is an exploratory endpoint to generate data for future prospective evaluation.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.

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Trials testing the same drug.

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