Trial Outcomes & Findings for Pilot Phase 2 Study Whole Brain Radiation Therapy With Simultaneous Integrated Boost for Patients With Brain Metastases (NCT NCT03189381)

Last Updated: 2024-06-28

Results Overview

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.

Recruitment status

TERMINATED

Study phase

Target enrollment

20 participants

Primary outcome timeframe

6 Months

Results posted on

2024-06-28

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A Standard prophylactic intracranial irradiation (PCI) dose Cohort A: whole-brain radiation therapy dose (WBRT) = 25 Gy, simultaneous integrated boost (SIB) dose = 42 Gy, # of daily fractions = 10, SIB dose in equivalent dose in 2 Gray fractions (EQD2) = 49.7 Gy	Cohort B Low prophylactic intracranial irradiation (PCI) dose Cohort B: Cohort B - whole-brain radiation therapy dose (WBRT) dose = 20 Gy, simultaneous integrated boost (SIB) dose = 40 Gy, # of daily fractions = 8, SIB dose in equivalent dose in 2 Gray fractions (EQD2) = 50.0 Gy
Overall Study STARTED	20	0
Overall Study COMPLETED	19	0
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A Standard prophylactic intracranial irradiation (PCI) dose Cohort A: whole-brain radiation therapy dose (WBRT) = 25 Gy, simultaneous integrated boost (SIB) dose = 42 Gy, # of daily fractions = 10, SIB dose in equivalent dose in 2 Gray fractions (EQD2) = 49.7 Gy	Cohort B Low prophylactic intracranial irradiation (PCI) dose Cohort B: Cohort B - whole-brain radiation therapy dose (WBRT) dose = 20 Gy, simultaneous integrated boost (SIB) dose = 40 Gy, # of daily fractions = 8, SIB dose in equivalent dose in 2 Gray fractions (EQD2) = 50.0 Gy
Overall Study Death	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 6 Months

Population: Includes the patients evaluable for in-brain distant failure at 6 months. There were no patients accrued in cohort B.

Outcome measures

Outcome measures
Measure	Cohort A n=9 Participants Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy
In-Brain Distant Failure Rate	0.444 proportion of patients Interval 0.137 to 0.788	—

SECONDARY outcome

Timeframe: 6 Months

Population: Includes patients evaluable for 6-month outcomes. There were no patients accrued in cohort B.

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.

Outcome measures

Outcome measures
Measure	Cohort A n=9 Participants Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy
Treated Lesion Local Control	1.000 survival probability Interval 1.0 to 1.0	—

SECONDARY outcome

Timeframe: 6 Months

Population: Includes patients evaluable for 6-month outcomes. There were no patients accrued in cohort B.

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.

Outcome measures

Outcome measures
Measure	Cohort A n=9 Participants Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy
Overall Survival for Evaluable Patients	1.000 survival probability Interval 1.0 to 1.0	—

SECONDARY outcome

Timeframe: 6 Months

Population: Includes patients evaluable for 6-month outcomes. There were no patients accrued in cohort B.

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 from 0-12 (higher scores are better). Retention (%) is the percentage of words recalled and ranges from 0-100 (higher values represent better recall). The recognition discrimination score is tested by a series of yes/no responses from the participant identifying 12 words from a list of 24 and subtracts the number of true positives minus the true negatives (higher values are better).

Outcome measures

Outcome measures
Measure	Cohort A n=9 Participants Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy
Change in Neurocognitive Function From Baseline to 6 Months Total Recall Raw Score	-1.00 difference in score on a scale Interval -2.25 to 0.25	—
Change in Neurocognitive Function From Baseline to 6 Months Delayed Recall Raw Score	-1.00 difference in score on a scale Interval -2.75 to 0.25	—
Change in Neurocognitive Function From Baseline to 6 Months Recognition Discrimination Index Raw Score	0.00 difference in score on a scale Interval -2.75 to 0.0	—

SECONDARY outcome

Timeframe: 6 Months

Population: Includes patients evaluable for 6-month outcomes. There were no patients accrued in cohort B.

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 (range: 0-24), functional well-being (range: 0-28), bone marrow transplant (BMT) (range: 0-40), and brain cancer (range: 0-92) subscale scores. These subscale scores were then summed to obtain the trail outcome index (range: 0-148), bone marrow transplant (FACT-BMT) (range: 0-96), general (FACT-G) (range: 0-108), and FACT-Br (range: 0-200) total scores. The higher the score, the better the QoL.

Outcome measures

Outcome measures
Measure	Cohort A n=9 Participants Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy
Change in Health-Related Quality of Life (QoL) From Baseline to 6 Months Physical Well-Being	-1.00 scores on a scale Interval -2.0 to 1.0	—
Change in Health-Related Quality of Life (QoL) From Baseline to 6 Months Social/Family Well-Being	-2.00 scores on a scale Interval -2.0 to 1.0	—
Change in Health-Related Quality of Life (QoL) From Baseline to 6 Months Emotional Well-Being	-1.00 scores on a scale Interval -2.0 to 0.0	—
Change in Health-Related Quality of Life (QoL) From Baseline to 6 Months Functional Well-Being	-1.00 scores on a scale Interval -3.0 to 1.0	—
Change in Health-Related Quality of Life (QoL) From Baseline to 6 Months Bone Marrow Transplant (BMT) Subscale	0.00 scores on a scale Interval -3.0 to 2.0	—
Change in Health-Related Quality of Life (QoL) From Baseline to 6 Months Trial Outcome Index	-4.00 scores on a scale Interval -6.0 to 1.0	—
Change in Health-Related Quality of Life (QoL) From Baseline to 6 Months FACT-G	-2.00 scores on a scale Interval -7.0 to 4.0	—
Change in Health-Related Quality of Life (QoL) From Baseline to 6 Months FACT-BMT	-1.00 scores on a scale Interval -8.0 to 3.83	—

SECONDARY outcome

Timeframe: 12 Months

Population: Includes patients evaluable for 6-month outcomes. There were no patients accrued in cohort B.

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".

Outcome measures

Outcome measures
Measure	Cohort A n=9 Participants Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy
Change in Performance Status Baseline to 3 Months	-10.00 difference in score on a scale Interval -10.0 to 10.0	—
Change in Performance Status Baseline to 6 Months	0.00 difference in score on a scale Interval 0.0 to 0.0	—
Change in Performance Status Baseline to 12 Months	0.00 difference in score on a scale Interval 0.0 to 5.0	—

SECONDARY outcome

Timeframe: Up To 39 Months

Population: Includes the patients marked as eligible who started treatment. There were no patients accrued in cohort B.

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.

Outcome measures

Outcome measures
Measure	Cohort A n=20 Participants Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy
Incidence of Early and Late Treatment-Related Adverse Effects Fatigue	50.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Alopecia	30.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Memory Impairment	25.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Headache	10.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Somnolence	10.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Blurred Vision	5.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Cognitive Disturbance	5.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Dermatitis Radiation	5.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Dry Skin	5.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Mucosal Infection	5.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Oral Pain	5.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Papulopustular Rash	5.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Pruritus	5.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Rash Maculo-Papular	5.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Skin and Subcutaneous Tissue Disorders	5.00 percentage of patients	—
Incidence of Early and Late Treatment-Related Adverse Effects Vomiting	5.00 percentage of patients	—

SECONDARY outcome

Timeframe: 6 Months

Population: Includes patients who started treatment and were deemed eligible for the study. There were no patients accrued in cohort B.

Outcome measures

Outcome measures
Measure	Cohort A n=20 Participants Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy
Overall Survival for Eligible Patients	0.700 survival probability Interval 0.451 to 0.853	—

SECONDARY outcome

Timeframe: 6 Months

Population: Includes patients evaluable for 6-month outcomes. There were no patients accrued in cohort B.

Outcome measures

Outcome measures
Measure	Cohort A n=9 Participants Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy
Change in Neurocognitive Function Retention Percentage Raw Score From Baseline to 6 Months	-3.00 percentage Interval -30.5 to 2.25	—

Adverse Events

Cohort A

Serious events: 9 serious events

Other events: 20 other events

Deaths: 15 deaths

Cohort B

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Kevin Shiue

Indiana University (IU)

Phone: 317 944 2524

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort A n=20 Participants Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy	Total n=20 Participants Total of all reporting groups
Age, Continuous	59.8 years STANDARD_DEVIATION 15.12 • n=5 Participants	—	59.8 years STANDARD_DEVIATION 15.12 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	—	11 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	—	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	—	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	—	3 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	—	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	—	20 participants n=5 Participants
Primary Cancer Diagnosis Bladder	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Primary Cancer Diagnosis Breast	5 Participants n=5 Participants	—	5 Participants n=5 Participants
Primary Cancer Diagnosis Colon	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Primary Cancer Diagnosis Kidney	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Primary Cancer Diagnosis Lung	11 Participants n=5 Participants	—	11 Participants n=5 Participants
Primary Cancer Diagnosis Skin - Scalp and Neck	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Number of Lesions at Baseline	7.00 lesions n=5 Participants	—	7.00 lesions n=5 Participants
Number of Boosted Lesions at Baseline	7.00 lesions n=5 Participants	—	7.00 lesions n=5 Participants

Measure	Cohort A n=20 participants at risk Standard PCI dose Cohort A: Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy	Cohort B Low PCI dose Cohort B: Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy
Gastrointestinal disorders Abdominal pain	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Infections and infestations Breast infection	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Psychiatric disorders Confusion	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Metabolism and nutrition disorders Dehydration	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Nervous system disorders Dysarthria	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Gastrointestinal disorders Dysphagia	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Nervous system disorders Encephalopathy	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Injury, poisoning and procedural complications Fall	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
General disorders Gait disturbance	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Psychiatric disorders Hallucinations	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Respiratory, thoracic and mediastinal disorders Hypoxia	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Investigations Neutrophil count decreased	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Infections and infestations Sepsis	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Vascular disorders Thromboembolic event	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.
Infections and infestations Urinary tract infection	5.0% 1/20 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.	— 0/0 • Adverse events were collected throughout the study and assessed up to 39 months There were no patients accrued in cohort B. Therefore, the number at risk for all events is zero.