Liver Cancer
Conditions
Keywords
adult primary hepatocellular carcinoma, advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer
Brief summary
This is a phase I trial studying the side effects and best dose of stereotactic radiation therapy (SRT) in treating patients with advanced liver cancer. Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue.
Detailed description
This is a phase I trial studying the side effects and best dose of stereotactic radiation therapy (SRT) in treating patients with advanced liver cancer. Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Participants must have pathologically confirmed hepatocellular carcinoma with at least one tumor with a maximum diameter of ≤ 8 cm and must have Karnofsky performance status ≥ 60% and a life expectancy of at least 12 weeks. The primary objective is determining the safety of hypofractionated stereotactic radiotherapy in patients with advanced hepatocellular carcinoma by using toxicity profiles described in the Common Terminology Criteria for Adverse Events (CTCAE) V.3.0. Secondary objectives are determining the maximal tolerable SRT dose, objective tumor response rate, the value of 4-Dimensional Computed Tomography (4DCT) in liver cancer planning, and the value of breath gating in liver cancer stereotactic body radiotherapy (SBRT). After completion of study therapy, participants are followed at 1 and 3 months.
Interventions
RADIATIONstereotactic body radiation therapy
Undergo radiotherapy
Sponsors
National Cancer Institute (NCI)
University of Nebraska
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed advanced hepatocellular carcinoma (HCC) * Measurable disease, defined as ≥ 1 unidimensionally target lesion that can be accurately measured by CT scan or MRI according to RECIST and must have a maximum diameter ≤ 8 cm * Child-Pugh class A-B cirrhotic status * Karnofsky performance status 60-100% * Life expectancy ≥ 12 weeks * White blood cell count (WBC) ≥ 2,000/μL * Platelet count ≥ 60,000/mm³ * Hemoglobin ≥ 8.5 g/dLINR ≤ 2.3 * More than 6 months since prior myocardial infarction * Prior systemic chemotherapy allowed * At least 6 weeks since prior non-radiation local therapy (e.g., surgery, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) * Concurrent therapeutic anticoagulation (e.g., warfarin or heparin) allowed provided that no prior evidence of underlying abnormality in Prothrombin time (PT/INR) and partial thromboplastin time (PTT) exists
Exclusion criteria
* No known central nervous system (CNS) tumors, including metastatic brain disease * No malignancy within the past 3 years that is distinct in its primary site or histology from HCC, except for carcinoma in situ of the cervix, treated basal cell carcinoma, or superficial bladder tumors (i.e., Ta, Tis, and T1), or any other cancer that has been curatively treated \> 3 years prior to study entry * No renal failure requiring hemodialysis or peritoneal dialysis * No uncontrolled intercurrent illness including, but not limited to, any of the following: * Ongoing or active infection \> grade 2 * New York Heart Association (NYHA) class II-IV congestive heart failure * Active coronary artery disease * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin * Uncontrolled hypertension * Condition that could jeopardize the safety of the patient or study compliance * No history of variceal bleeding where the varices have not been eradicated or decompressed by shunt placement * No condition that would prevent the patient from undergoing marker implantation * Not pregnant or nursing/negative pregnancy test * No substance abuse, medical, psychological, or social condition that may interfere with the patient's participation in the study or evaluation of the study results * No prior radiotherapy to the liver
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Safety of Hypofractionated Stereotactic Radiotherapy in Patients With Advanced Hepatocellular Carcinoma | Up to 1 month after Stereotactic Radiation Therapy (SRT) treatment | Toxicity as assessed by NCI CTCAE v3.0 (Adverse Events). Due to delayed toxicities attributable to radiotherapy, all toxicities observed within 1 month after SRT will be scored. Dose limiting toxicity (DLT) is defined as any of following toxicities, that is possibly, probably or definitely related to Stereotactic Radiation Therapy (SRT) occurring within 1 month from the start of treatment: 1. grade 4 or 5 hepatic 2. grade 4 or 5 gastrointestinal 3. grade 4 or 5 thrombocytopenia 4. grade 4 hepatic liver enzyme elevations persisting for ≥ 5 days 5. any adverse event requiring interruption of therapy by ≥ 2 weeks (14 calendar days). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response at 1-month Post SRT | Measured from first day of SRT to 1-month post SRT. | Response rate from tumor measurement at 1-month post-SRT |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 10 Gy x 5 Dose Level 10 Gy x 5 | 3 |
| 12 Gy x 5 Dose level 12 Gy x 5 | 3 |
| 14 Gy x 5 Dose level 14 Gy x 5 | 1 |
| Total | 7 |
Baseline characteristics
| Characteristic | 10 Gy x 5 | 12 Gy x 5 | 14 Gy x 5 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 00 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 1 participants | 7 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 1 |
Outcome results
Primary
The Safety of Hypofractionated Stereotactic Radiotherapy in Patients With Advanced Hepatocellular Carcinoma
Toxicity as assessed by NCI CTCAE v3.0 (Adverse Events). Due to delayed toxicities attributable to radiotherapy, all toxicities observed within 1 month after SRT will be scored. Dose limiting toxicity (DLT) is defined as any of following toxicities, that is possibly, probably or definitely related to Stereotactic Radiation Therapy (SRT) occurring within 1 month from the start of treatment: 1. grade 4 or 5 hepatic 2. grade 4 or 5 gastrointestinal 3. grade 4 or 5 thrombocytopenia 4. grade 4 hepatic liver enzyme elevations persisting for ≥ 5 days 5. any adverse event requiring interruption of therapy by ≥ 2 weeks (14 calendar days).
Time frame: Up to 1 month after Stereotactic Radiation Therapy (SRT) treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 Gy x 5 | The Safety of Hypofractionated Stereotactic Radiotherapy in Patients With Advanced Hepatocellular Carcinoma | Experienced at least 1 Toxicity | 0 Participants |
| 10 Gy x 5 | The Safety of Hypofractionated Stereotactic Radiotherapy in Patients With Advanced Hepatocellular Carcinoma | Experienced No Toxicities | 3 Participants |
| 12 Gy x 5 | The Safety of Hypofractionated Stereotactic Radiotherapy in Patients With Advanced Hepatocellular Carcinoma | Experienced No Toxicities | 3 Participants |
| 12 Gy x 5 | The Safety of Hypofractionated Stereotactic Radiotherapy in Patients With Advanced Hepatocellular Carcinoma | Experienced at least 1 Toxicity | 0 Participants |
| 14 Gy x 5 | The Safety of Hypofractionated Stereotactic Radiotherapy in Patients With Advanced Hepatocellular Carcinoma | Experienced No Toxicities | 0 Participants |
| 14 Gy x 5 | The Safety of Hypofractionated Stereotactic Radiotherapy in Patients With Advanced Hepatocellular Carcinoma | Experienced at least 1 Toxicity | 1 Participants |
Secondary
Response at 1-month Post SRT
Response rate from tumor measurement at 1-month post-SRT
Time frame: Measured from first day of SRT to 1-month post SRT.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 Gy x 5 | Response at 1-month Post SRT | PR | 3 Participants |
| 10 Gy x 5 | Response at 1-month Post SRT | SD | 0 Participants |
| 12 Gy x 5 | Response at 1-month Post SRT | PR | 2 Participants |
| 12 Gy x 5 | Response at 1-month Post SRT | SD | 1 Participants |
| 14 Gy x 5 | Response at 1-month Post SRT | SD | 1 Participants |
| 14 Gy x 5 | Response at 1-month Post SRT | PR | 0 Participants |