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

• 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: 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
• Information provided by (Responsible Party): Theodore Sunki Hong, Massachusetts General Hospital

Tracking Information

• First Submitted Date: September 11, 2009
• First Posted Date: September 15, 2009
• Results First Submitted Date: December 7, 2017
• Results First Posted Date: January 31, 2018
• Last Update Posted Date: August 15, 2018
• Study Start Date: August 2009
• Actual Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 5, 2018)

• 2 Year Local Control Rate [ Time Frame: 2 years ]
  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).
• Median Overall Survival [ Time Frame: 5 years ]
  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.

Original Primary Outcome Measures (submitted: September 14, 2009)

• To demonstrate the 2 year LC of >85% with proton beam irradiation for unresectable liver tumors. [ Time Frame: 2 years ]
• To evaluate 5 year overall survival and local control. [ Time Frame: 5 years ]

Current Secondary Outcome Measures (submitted: January 5, 2018)

• Number of Participants With Treatment Related Adverse Events ≥ Grade 3 [ Time Frame: 2 years ]
  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).
• Patterns of Failure [ Time Frame: 2 years ]
  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

Original Secondary Outcome Measures (submitted: September 14, 2009)

• To determine safety and tolerance of this treatment program. [ Time Frame: 2 years ]
• To evaluate tumor response, patterns of failure, and survival in this patient population. [ Time Frame: 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Proton Beam Irradiation for the Treatment of Unresectable Hepatocellular Cancer and Cholangiocarcinoma
• Official Title: Phase II Study of Proton Beam Irradiation for the Treatment of Unresectable Hepatocellular Cancer and Cholangiocarcinoma
• Brief 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.

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Liver Cancer

Intervention

Radiation: Proton Beam Irradiation

Given once a day, 5 days a week, for 3 weeks

Study Arms

Experimental: Proton Beam Irradiation

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

Intervention: Radiation: Proton Beam Irradiation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 5, 2018): 83
• Original Estimated Enrollment (submitted: September 14, 2009): 40
• Actual Study Completion Date: July 2018
• Actual Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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:

• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00976898
• Other Study ID Numbers: 09-131; P01CA021239 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Theodore Sunki Hong, Massachusetts General Hospital
• Original Responsible Party: Theodore S. Hong, MD, Massachusetts General Hospital
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current

Collaborators

• Dana-Farber Cancer Institute
• Brigham and Women's Hospital
• National Cancer Institute (NCI)
• M.D. Anderson Cancer Center
• University of Pennsylvania

Investigators

• Principal Investigator: Theodore S. Hong, MD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: July 2018