Trial Outcomes & Findings for Dose Escalation Study for Primary Hepatocellular Carcinoma (NCT NCT00243841)

NCT ID: NCT00243841

Last Updated: 2018-12-13

Results Overview

Number of patients experiencing a Dose Limiting Toxicity during the Phase I portion of the trial.

Recruitment status

COMPLETED

Study phase

Target enrollment

77 participants

Primary outcome timeframe

6 weeks

Results posted on

2018-12-13

Participant Flow

This is a Phase I/II study. Phase I is a dose finding study, and Phase II will use the doses determined by the Phase I portion to further look at efficacy. During Phase I, it was determined to look at Childs A patients separately from Childs B patients. Patients who were Childs B required a dose reduction during Phase I.

Participant milestones

Participant milestones
Measure	Phase I: 36 Gy Patients will receive 1200 cGy x 3 fractions of radiation	Phase I: 42 Gy Patients will receive 1400 cGy x 3 fractions of radiation	Phase I: 40 Gy Patients will receive 800 cGy x 5 fractions of radiation for Childs B only (dose reduction)	Phase I: 48 Gy Patients will receive 1600 cGy x 3 fractions of radiation for Childs A only	Phase II Childs A Patients in Phase II with a score of Childs A Will receive 3 fractions (48 Gy) of radiation over 5-10 days	Phase II Childs B Patients in Phase II with a score of Childs B will receive 5 fractions (40 Gy) of radiation over 2-6 weeks.
Overall Study STARTED	3	6	5	3	39	21
Overall Study COMPLETED	3	6	4	3	39	19
Overall Study NOT COMPLETED	0	0	1	0	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I: 36 Gy Patients will receive 1200 cGy x 3 fractions of radiation	Phase I: 42 Gy Patients will receive 1400 cGy x 3 fractions of radiation	Phase I: 40 Gy Patients will receive 800 cGy x 5 fractions of radiation for Childs B only (dose reduction)	Phase I: 48 Gy Patients will receive 1600 cGy x 3 fractions of radiation for Childs A only	Phase II Childs A Patients in Phase II with a score of Childs A Will receive 3 fractions (48 Gy) of radiation over 5-10 days	Phase II Childs B Patients in Phase II with a score of Childs B will receive 5 fractions (40 Gy) of radiation over 2-6 weeks.
Overall Study Physician Decision	0	0	1	0	0	2

Baseline Characteristics

Dose Escalation Study for Primary Hepatocellular Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I n=17 Participants Dose escalation to 48 Gy (16Gy/fraction) in Childs A and to 42 Gy (14 Gy/fraction) down to 40 Gy (8Gy/fraction) for Childs B	Phase II Childs A n=39 Participants Patients in Phase II with a score of Childs A Will receive 3 fractions (48 Gy) of radiation over 5-10 days	Phase II Childs B n=21 Participants Patients in Phase II with a score of Childs B will receive 5 fractions (40 Gy) of radiation over 2-6 weeks.	Total n=77 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	27 Participants n=7 Participants	17 Participants n=5 Participants	54 Participants n=4 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	12 Participants n=7 Participants	4 Participants n=5 Participants	23 Participants n=4 Participants
Age, Continuous	60.8 years STANDARD_DEVIATION 9.76 • n=5 Participants	60.9 years STANDARD_DEVIATION 10.62 • n=7 Participants	58.5 years STANDARD_DEVIATION 7.55 • n=5 Participants	60.2 years STANDARD_DEVIATION 9.6 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	11 Participants n=7 Participants	4 Participants n=5 Participants	16 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	28 Participants n=7 Participants	17 Participants n=5 Participants	61 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	38 Participants n=7 Participants	20 Participants n=5 Participants	74 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	30 Participants n=7 Participants	19 Participants n=5 Participants	64 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: All patients who received treatment in Phase I

Number of patients experiencing a Dose Limiting Toxicity during the Phase I portion of the trial.

Outcome measures

Outcome measures
Measure	Phase I: 36 Gy n=3 Participants Patients will receive 1200 cGy x 3 fractions of radiation	Phase I: 42 Gy n=6 Participants Patients will receive 1400 cGy x 3 fractions of radiation	Phase I: 40 Gy n=5 Participants Patients will receive 800 cGy x 5 fractions of radiation for Childs B only (dose reduction)	Phase I: 48 Gy n=3 Participants Patients will receive 1600 cGy x 3 fractions of radiation for Childs A only
Number of Patients With DLTs	0 Participants	2 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 6 months

Population: All patients who received treatment and had a post-baseline assessment.

Percent of patients and the 95% Binomial Confidence interval who were free of in-field progression at 6 months following treatment for the patients in Phase II

Outcome measures

Outcome measures
Measure	Phase I: 36 Gy n=39 Participants Patients will receive 1200 cGy x 3 fractions of radiation	Phase I: 42 Gy n=21 Participants Patients will receive 1400 cGy x 3 fractions of radiation	Phase I: 40 Gy Patients will receive 800 cGy x 5 fractions of radiation for Childs B only (dose reduction)	Phase I: 48 Gy Patients will receive 1600 cGy x 3 fractions of radiation for Childs A only
6 Month Local In-field Control	92.3 percentage of participants Interval 79.1 to 98.4	87.5 percentage of participants Interval 61.7 to 98.5	—	—

SECONDARY outcome

Timeframe: up to 4 yrs

Population: All pts who received treatment and had a post-baseline assessment

Kaplan-Meier Analyses will be used to calculate the median and 95% Confidence Interval for the time until in-field failure. This will be calculated from the time of treatment until the time of in-field failure. If a patient did not have in-field failure, the patient will be censored at their last evaluation date.

Outcome measures

Outcome measures
Measure	Phase I: 36 Gy n=39 Participants Patients will receive 1200 cGy x 3 fractions of radiation	Phase I: 42 Gy n=19 Participants Patients will receive 1400 cGy x 3 fractions of radiation	Phase I: 40 Gy Patients will receive 800 cGy x 5 fractions of radiation for Childs B only (dose reduction)	Phase I: 48 Gy Patients will receive 1600 cGy x 3 fractions of radiation for Childs A only
Time to In-field Failure	NA months insufficient number of participants with events to estimate	32.2 months Interval 32.2 to insufficient number of participants with events to estimate	—	—

SECONDARY outcome

Timeframe: Up to 8 years

Population: all patients who received treatment and had a post-baseline assessment

Kaplan-Meier Analysis will be used to calculate the median and 95% CI for overall survival. This will be calculated from the time of treatment until death. If a patient did not die, the patient will be censored at their last known alive date.

Outcome measures

Outcome measures
Measure	Phase I: 36 Gy n=39 Participants Patients will receive 1200 cGy x 3 fractions of radiation	Phase I: 42 Gy n=19 Participants Patients will receive 1400 cGy x 3 fractions of radiation	Phase I: 40 Gy Patients will receive 800 cGy x 5 fractions of radiation for Childs B only (dose reduction)	Phase I: 48 Gy Patients will receive 1600 cGy x 3 fractions of radiation for Childs A only
Overall Survival	50.43 months Interval 30.88 to 68.59	21.40 months Interval 10.45 to insufficient number of participants with events to estimate	—	—

SECONDARY outcome

Timeframe: up to 4 years

Population: All patients who received treatment

Number of unique patients who had grade 3 or 4 adverse events that were possibly, probably or definitely related to study treatment.