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Proton Beam Irradiation for the Treatment of Unresectable Hepatocellular Cancer and Cholangiocarcinoma

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ClinicalTrials.gov Identifier: NCT00976898
Recruitment Status : Completed
First Posted : September 15, 2009
Results First Posted : January 31, 2018
Last Update Posted : August 15, 2018
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
University of Pennsylvania
Information provided by (Responsible Party):
Theodore Sunki Hong, Massachusetts General Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Liver Cancer
Intervention Radiation: Proton Beam Irradiation
Enrollment 83
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Proton Beam Irradiation
Hide Arm/Group Description

This is a single arm study. All study participants will receive proton radiation therapy.

Proton Beam Irradiation: Given once a day, 5 days a week, for 3 weeks

Period Title: Overall Study
Started 83
Completed 78
Not Completed 5
Reason Not Completed
Protocol Violation             1
Adverse Event             1
Physician Decision             1
Liver Transplant             1
Progressive Disease             1
Arm/Group Title Proton Beam Irradiation
Hide Arm/Group Description

This is a single arm study. All study participants will receive proton radiation therapy.

Proton Beam Irradiation: Given once a day, 5 days a week, for 3 weeks

Overall Number of Baseline Participants 83
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 83 participants
67.6
(29.9 to 89.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants
Female
32
  38.6%
Male
51
  61.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants
White
76
  91.6%
Black
4
   4.8%
Asian
1
   1.2%
Hispanic (white or black)
1
   1.2%
Unknown
1
   1.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 83 participants
83
Underlying Liver Disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants
Hepatitis C Virus (HCV) (± Others)
28
  33.7%
No HCV but Hepatitis B Virus (HBV) (± Others)
6
   7.2%
No HCV/HBV but Ethyl Hepatocellularalcohol (EtOH)
8
   9.6%
No HCV/HBV/EtOH but nonalcoholic steatohepatitis
3
   3.6%
Other
2
   2.4%
None
36
  43.4%
ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants
0
28
  33.7%
1
52
  62.7%
2
3
   3.6%
[1]
Measure Description:

Eastern Cooperative Oncology Group (ECOG) score:

  • 0 – Asymptomatic (Fully active, able to carry on all predisease activities without restriction)
  • 1 – Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work)
  • 2 – Symptomatic, <50% in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours)
Child-Turcotte-Pugh Class   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants
A
66
  79.5%
B
15
  18.1%
C
0
   0.0%
No Cirrhosis
4
   4.8%
[1]
Measure Description: Child-Turcotte-Pugh Class is used to evaluate the prognosis of chronic liver disease (primarily cirrhosis). Classes are determined using 5 clinical measures of liver disease with 1 to 3 points given for each measure, with more points given for less favorable clinical criteria. The 5 measures are total bilirubin, serum albumin, prothrombin time/international normalized ratio (INR), Ascites, and hepatic encephalopathy grade. The classes are A (5-6 points), B (7-9 points), and C (10-15 points) with 'A' having the best survival outcomes and C having the worst.
Disease Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants
Locally Recurrent
5
   6.0%
Newly Diagnosed
78
  94.0%
Number of Nodular Tumors  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants
1
66
  79.5%
2
15
  18.1%
3
4
   4.8%
Previous Therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants
Any surgical resection
4
   4.8%
Any transarterial chemoembolization
5
   6.0%
Any radiofrequency ablation
2
   2.4%
Any chemotherapy
27
  32.5%
Any other
15
  18.1%
None
45
  54.2%
1.Primary Outcome
Title 2 Year Local Control Rate
Hide Description The percentage of participants with local control after two years as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. The duration of control was measured from the start of treatment. Local control is the absence of local failure. Local Failure is defined as evidence of tumor growth/regrowth in any direction beyond that present of the pre-treatment imaging studies in the treated lesion(s).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Proton Beam Irradiation
Hide Arm/Group Description:

This is a single arm study. All study participants will receive proton radiation therapy.

Proton Beam Irradiation: Given once a day, 5 days a week, for 3 weeks

Overall Number of Participants Analyzed 83
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
94.4
(87.2 to 98.2)
2.Primary Outcome
Title Median Overall Survival
Hide Description The median survival time in months as measured from the start of treatment until death due to any cause or until the participants is censored. Participants are censored at the date of their last follow-up.
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Proton Beam Irradiation
Hide Arm/Group Description:

This is a single arm study. All study participants will receive proton radiation therapy.

Proton Beam Irradiation: Given once a day, 5 days a week, for 3 weeks

Overall Number of Participants Analyzed 83
Median (95% Confidence Interval)
Unit of Measure: Months
49.9 [1] 
(17.8 to NA)
[1]
Upper bound not reached because of living subjects
3.Secondary Outcome
Title Number of Participants With Treatment Related Adverse Events ≥ Grade 3
Hide Description Summary of the proton radiation related grade 3 or greater adverse events that participants experienced. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE v3).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Proton Beam Irradiation
Hide Arm/Group Description:

This is a single arm study. All study participants will receive proton radiation therapy.

Proton Beam Irradiation: Given once a day, 5 days a week, for 3 weeks

Overall Number of Participants Analyzed 83
Measure Type: Count of Participants
Unit of Measure: Participants
Liver Failure
1
   1.2%
Platelets
1
   1.2%
Ascites (nonmalignant)
1
   1.2%
Ulcer, GI - stomach
1
   1.2%
Bilirubin (hyperbilirubinemia)
1
   1.2%
4.Secondary Outcome
Title Patterns of Failure
Hide Description A summary of the patterns of treatment failure, shown as the number of participants that fall into each category at the end of study follow-up
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Proton Beam Irradiation
Hide Arm/Group Description:

This is a single arm study. All study participants will receive proton radiation therapy.

Proton Beam Irradiation: Given once a day, 5 days a week, for 3 weeks

Overall Number of Participants Analyzed 83
Measure Type: Count of Participants
Unit of Measure: Participants
Alive, no progression
26
  31.3%
Distant metastases
38
  45.8%
Local failure and distant metastases
3
   3.6%
Isolated local failure
5
   6.0%
Dead of disease, no progression
2
   2.4%
Dead of other causes, no progression
9
  10.8%
Time Frame Adverse event information was collected from the start of treatment until 30 days after the last study visit. Radiation was delivered in 15 fractions Monday through Friday over a period of three weeks. Follow-up visits occurred at 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 months post treatment. Median follow-up was 19.5 months.
Adverse Event Reporting Description Adverse events were assessed with the use of regularly scheduled visits which involved physical exams, CT and/or MRI scans, laboratory tests, and patient self reporting. If an adverse event did not match any of the existing CTCAE 3 terms, it was noted as being 'other'. Adverse events noted as being 'other' were only grouped together by organ system due to incomplete data about what specific adverse event was being recorded as 'other'.
 
Arm/Group Title Proton Beam Irradiation
Hide Arm/Group Description

This is a single arm study. All study participants will receive proton radiation therapy.

Proton Beam Irradiation: Given once a day, 5 days a week, for 3 weeks

All-Cause Mortality
Proton Beam Irradiation
Affected / at Risk (%)
Total   11/83 (13.25%)    
Show Serious Adverse Events Hide Serious Adverse Events
Proton Beam Irradiation
Affected / at Risk (%) # Events
Total   8/83 (9.64%)    
Gastrointestinal disorders   
Ascites (non-malignant)  1  1/83 (1.20%)  1
General disorders   
Fatigue (asthenia, lethargy, malaise)  1  1/83 (1.20%)  1
Infections and infestations   
Infection with unknown ANC - Abdomen NOS  1  1/83 (1.20%)  1
Injury, poisoning and procedural complications   
Fracture  1  2/83 (2.41%)  2
Investigations   
Bilirubin (hyperbilirubinemia)  1  1/83 (1.20%)  1
Platelets  1  1/83 (1.20%)  2
Metabolism and nutrition disorders   
Sodium, serum-low (hyponatremia)  1  1/83 (1.20%)  1
Nervous system disorders   
Encephalopathy  1  1/83 (1.20%)  1
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/83 (1.20%)  1
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Proton Beam Irradiation
Affected / at Risk (%) # Events
Total   81/83 (97.59%)    
Blood and lymphatic system disorders   
Blood/Bone Marrow - Other  1  16/83 (19.28%)  47
Hemoglobin  1  9/83 (10.84%)  25
Cardiac disorders   
Cardiac General - Other  1  5/83 (6.02%)  14
Gastrointestinal disorders   
Ascites (non-malignant)  1  20/83 (24.10%)  43
Constipation  1  14/83 (16.87%)  33
Diarrhea  1  18/83 (21.69%)  31
Distension/bloating, abdominal  1  16/83 (19.28%)  29
Gastrointestinal - Other  1  13/83 (15.66%)  29
Heartburn/dyspepsia  1  11/83 (13.25%)  25
Nausea  1  40/83 (48.19%)  104
Vomiting  1  18/83 (21.69%)  22
General disorders   
Edema: limb  1  22/83 (26.51%)  60
Extremity-lower (gait/walking)  1  5/83 (6.02%)  12
Fatigue (asthenia, lethargy, malaise)  1  67/83 (80.72%)  316
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)  1  9/83 (10.84%)  25
Pain - Chest/thorax NOS  1  6/83 (7.23%)  8
Pain - Other  1  14/83 (16.87%)  33
Rigors/chills  1  9/83 (10.84%)  13
Injury, poisoning and procedural complications   
Bruising (in absence of Grade 3 or 4 thrombocytopenia)  1  8/83 (9.64%)  23
Fracture  1  7/83 (8.43%)  20
Investigations   
Alkaline phosphatase  1  13/83 (15.66%)  40
ALT, SGPT (serum glutamic pyruvic transaminase)  1  11/83 (13.25%)  41
AST, SGOT(serum glutamic oxaloacetic transaminase)  1  21/83 (25.30%)  75
Bilirubin (hyperbilirubinemia)  1  18/83 (21.69%)  79
Leukocytes (total WBC)  1  7/83 (8.43%)  21
Metabolic/Laboratory - Other  1  5/83 (6.02%)  10
Neutrophils/granulocytes (ANC/AGC)  1  7/83 (8.43%)  12
Platelets  1  24/83 (28.92%)  90
Weight loss  1  12/83 (14.46%)  40
Metabolism and nutrition disorders   
Anorexia  1  38/83 (45.78%)  92
Glucose, serum-high (hyperglycemia)  1  9/83 (10.84%)  34
Sodium, serum-low (hyponatremia)  1  8/83 (9.64%)  16
Musculoskeletal and connective tissue disorders   
Arthritis (non-septic)  1  5/83 (6.02%)  10
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized  1  8/83 (9.64%)  13
Musculoskeletal/Soft Tissue - Other  1  7/83 (8.43%)  15
Pain - Abdomen NOS  1  36/83 (43.37%)  136
Pain - Back  1  12/83 (14.46%)  21
Pain - Chest wall  1  9/83 (10.84%)  17
Pain - Extremity-limb  1  9/83 (10.84%)  19
Pain - Joint  1  8/83 (9.64%)  16
Nervous system disorders   
Dizziness  1  11/83 (13.25%)  25
Encephalopathy  1  5/83 (6.02%)  6
Memory impairment  1  5/83 (6.02%)  9
Neuropathy: sensory  1  5/83 (6.02%)  18
Pain - Head/headache  1  6/83 (7.23%)  11
Somnolence/depressed level of consciousness  1  5/83 (6.02%)  5
Psychiatric disorders   
Insomnia  1  10/83 (12.05%)  25
Mood alteration - Anxiety  1  10/83 (12.05%)  22
Depression  1  8/83 (9.64%)  24
Renal and urinary disorders   
Urinary frequency/urgency  1  8/83 (9.64%)  18
Urine color change  1  5/83 (6.02%)  5
Respiratory, thoracic and mediastinal disorders   
Cough  1  13/83 (15.66%)  23
Dyspnea (shortness of breath)  1  23/83 (27.71%)  38
Pleural effusion (non-malignant)  1  7/83 (8.43%)  13
Pulmonary/Upper Respiratory - Other  1  7/83 (8.43%)  17
Skin and subcutaneous tissue disorders   
Dermatology/Skin - Other  1  13/83 (15.66%)  41
Hyperpigmentation  1  13/83 (15.66%)  32
Pruritus/itching  1  6/83 (7.23%)  13
Rash/desquamation  1  5/83 (6.02%)  8
Rash: dermatitis associated with radiation - Chemoradiation  1  5/83 (6.02%)  5
Rash: dermatitis associated with radiation - Radiation  1  51/83 (61.45%)  194
Ulceration  1  5/83 (6.02%)  8
Vascular disorders   
Hypertension  1  5/83 (6.02%)  10
Hypotension  1  9/83 (10.84%)  16
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Theodore Sunki Hong, MD
Organization: Massachusetts General Hospital
Phone: 617-724-1159
Responsible Party: Theodore Sunki Hong, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00976898     History of Changes
Other Study ID Numbers: 09-131
P01CA021239 ( U.S. NIH Grant/Contract )
First Submitted: September 11, 2009
First Posted: September 15, 2009
Results First Submitted: December 7, 2017
Results First Posted: January 31, 2018
Last Update Posted: August 15, 2018