CompletedNCT00976898Updated Sep 15, 2025Results posted

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

An interventional study of Proton Beam Irradiation in Liver Cancer, sponsored by Massachusetts General Hospital. Completed at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-09-15.

Sponsored by Massachusetts General Hospital · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 83
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

In this study the investigators will be studying the effects of proton beam radiation therapy. This is a very accurate kind of treatment that has been shown to affect less normal tissue than a photon radiation beam. The accuracy allows the investigators to more safely increase the amount of radiation delivered to eliminate cancer. This accuracy will potentially reduce side effects that participants would normally experience using photon radiation therapy. The purpose of this study is to determine if radiation using proton beam therapy will kill the cancer cells in the participants liver.

Read the detailed description

Participants will receive treatment as an outpatient in the Francis H. Burr Proton Center at the Massachusetts General Hospital, the MD Anderson Proton Therapy Center or the Roberts Proton Therapy Center at the University of Pennsylvania.
Not everyone who participates in this study will be receiving the same dose of radiation. The dose received will be determined by the location of the tumor(s) within the liver.
Proton Beam radiation therapy to the liver will be given once a day, 5 days a week (Monday-Friday), for 2 weeks.
The following procedures will be performed once a week during treatment on days 1, 8 and 15, as well as on the last day of radiation: physical examination and blood tests.

Conditions studied

Liver Cancer

Browse trials for

Liver Neoplasms 1,391

Keywords

proton beam radiation

In context

Liver Neoplasms

1,391 studies on the registry are indexed under Liver Neoplasms; 345 are open to participants now.

This study's enrollment of 83 is above the median of 47 across 968 interventional studies indexed under Liver Neoplasms.

Browse Liver Neoplasms studies →

Lead sponsor

Massachusetts General Hospital is the lead sponsor of 2,537 studies on the registry; 447 are open to participants now.

Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Biopsy proven unresectable or locally recurrent hepatocellular cancer or intrahepatic cholangiocarcinoma. Patients with a single lesion must be 12cm or less in greatest dimension. For patients with two lesions, no lesion may be greater than 10cm in greatest dimension. For patients with three lesions, no lesion may be greater than 6cm in greatest dimension. Patients may have single or multinodular tumors (up to 3). There must be no evidence of extrahepatic tumor. Portal vein involvement or thrombosis is allowed.
Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20mm or greater with conventional techniques or as 10mm or greater with spiral CT scan.
Patients may have had prior chemotherapy, targeted biological therapy, surgery, transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for their disease as long as it is greater than 4 weeks from first protocol radiation treatment (6 weeks for nitrosoureas or mitomycin C). Patients may not have had prior radiation to the affected area.
18 years of age or older
Expected survival must be greater than three months
ECOG Performance Status of 0, 1 or 2
Normal organ and marrow function as outlined in the protocol
If patient has underlying cirrhosis, only Child-Pugh classification Group A or Group B patients should be included in this study.
Patients must be either surgically sterile or post-menopausal. Male and female patients of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of the study participation.
Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin

Exclusion criteria

Exclusion Criteria:

Women who are pregnant or lactating
Patients with evidence of non-hepatic metastatic disease
Local conditions or systemic illnesses which would reduce the local tolerance to radiation treatment, such as serious local injuries, active collagen vascular disease, etc.
Prior liver directed radiation treatment
Patients may have no serious medical illness, which may limit survival to less than 3 months
Patients may have no serious psychiatric illness/social situations which would limit compliance with study requirements
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Patients may not be receiving any other study agents
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 83 participants (actual)

Study arms

Experimental
Proton Beam Irradiation
This is a single arm study. All study participants will receive proton radiation therapy.
Radiation: Proton Beam Irradiation

Interventions

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

What researchers measure

Primary outcomes

2 Year Local Control Rate
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
Median Overall Survival
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

Secondary outcomes

Number of Participants With Treatment Related Adverse Events ≥ Grade 3
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
Patterns of Failure
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

Results

Posted Jan 31, 2018

Participant flow

Participant flow — Overall Study
Milestone	Proton Beam Irradiation
Started	83
Completed	78
Not completed	5
Withdrew: Protocol violation	1
Withdrew: Adverse event	1
Withdrew: Physician decision	1
Withdrew: Liver transplant	1
Withdrew: Progressive disease	1

Outcome measures

Primary2 Year Local Control Rate

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
Reported as:: Number · percentage of participants

2 Year Local Control Rate
percentage of participants	Proton Beam Irradiation
2 Year Local Control Rate	94.4 (87.2 to 98.2)

PrimaryMedian Overall Survival

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
Reported as:: Median · Months

Median Overall Survival
Months	Proton Beam Irradiation
Median Overall Survival	49.9 (17.8 to NA)

SecondaryNumber of Participants With Treatment Related Adverse Events ≥ Grade 3

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
Reported as:: Count of participants · Participants

Number of Participants With Treatment Related Adverse Events ≥ Grade 3
Participants	Proton Beam Irradiation
Liver Failure	1
Platelets	1
Ascites (nonmalignant)	1
Ulcer, GI - stomach	1
Bilirubin (hyperbilirubinemia)	1

SecondaryPatterns of Failure

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
Reported as:: Count of participants · Participants

Patterns of Failure
Participants	Proton Beam Irradiation
Alive, no progression	26
Distant metastases	38
Local failure and distant metastases	3
Isolated local failure	5
Dead of disease, no progression	2
Dead of other causes, no progression	9

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Proton Beam Irradiation	11/83 (13.3%)	8/83 (9.6%)	81/83 (97.6%)

Most frequent serious events

Most frequent serious events
Event	Proton Beam Irradiation
FractureInjury, poisoning and procedural complications	2/83
Ascites (non-malignant)Gastrointestinal disorders	1/83
Bilirubin (hyperbilirubinemia)Investigations	1/83
CoughRespiratory, thoracic and mediastinal disorders	1/83
EncephalopathyNervous system disorders	1/83
Fatigue (asthenia, lethargy, malaise)General disorders	1/83
Infection with unknown ANC - Abdomen NOSInfections and infestations	1/83
PlateletsInvestigations	1/83
Sodium, serum-low (hyponatremia)Metabolism and nutrition disorders	1/83

Most frequent other events

Showing 10 of 64

Most frequent other events
Event	Proton Beam Irradiation
Fatigue (asthenia, lethargy, malaise)General disorders	67/83
Rash: dermatitis associated with radiation - RadiationSkin and subcutaneous tissue disorders	51/83
NauseaGastrointestinal disorders	40/83
AnorexiaMetabolism and nutrition disorders	38/83
Pain - Abdomen NOSMusculoskeletal and connective tissue disorders	36/83
PlateletsInvestigations	24/83
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders	23/83
Edema: limbGeneral disorders	22/83
AST, SGOT(serum glutamic oxaloacetic transaminase)Investigations	21/83
Ascites (non-malignant)Gastrointestinal disorders	20/83

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Proton Beam Irradiation
Median	67.6 (29.9 to 89.7)

Sex: Female, Male
Sex: Female, Male(Participants)	Proton Beam Irradiation
Female	32
Male	51

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Proton Beam Irradiation
White	76
Black	4
Asian	1
Hispanic (white or black)	1
Unknown	1

Region of Enrollment
Region of Enrollment(participants)	Proton Beam Irradiation
United States	83

Underlying Liver Disease
Underlying Liver Disease(Participants)	Proton Beam Irradiation
Hepatitis C Virus (HCV) (± Others)	28
No HCV but Hepatitis B Virus (HBV) (± Others)	6
No HCV/HBV but Ethyl Hepatocellularalcohol (EtOH)	8
No HCV/HBV/EtOH but nonalcoholic steatohepatitis	3
Other	2
None	36

ECOG Performance Status
ECOG Performance Status(Participants)	Proton Beam Irradiation
0	28
1	52
2	3

Child-Turcotte-Pugh Class
Child-Turcotte-Pugh Class(Participants)	Proton Beam Irradiation
A	66
B	15
C	0
No Cirrhosis	4

Disease Status
Disease Status(Participants)	Proton Beam Irradiation
Locally Recurrent	5
Newly Diagnosed	78

2 further baseline measures are reported on the registry.

Study locations

4 sites

Massachusetts General Hospital
Boston, Massachusetts 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02115, United States
University of Pennsylvania, Roberts Proton Facility
Philadelphia, Pennsylvania, United States
University of Texas MD Anderson Cancer Center
Houston, Texas 77030, United States

References and documents

Study documents

Protocol and statistical analysis plan · Nov 16, 2015

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 15, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00976898
Lead sponsor: Massachusetts General Hospital
Collaborators: Dana-Farber Cancer Institute, Brigham and Women's Hospital, National Cancer Institute (NCI), M.D. Anderson Cancer Center, University of Pennsylvania
Responsible party: Hannah Roberts (Principal Investigator, Massachusetts General Hospital) — Principal investigator
First posted: Sep 15, 2009
Start date: Aug 2009
Primary completion: Mar 2017
Completion: Jul 2018
Results posted: Jan 31, 2018
Last update: Sep 15, 2025

Study contacts

Hannah J. Roberts, MD

principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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