A Study of Individualized Stereotactic Body Radiation Therapy (SBRT) for Intrahepatic Cancer

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01522937
• Collaborator: (none)
• Enrollment: 94
• Location: 1
• Arm: 1
• Duration (Months): 73
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This is a Phase II trial to characterize the safety and efficacy of individualized stereotactic body radiation therapy (SRBT) for patients who have had previous liver treatment or who have primary hepatocellular carcinoma (HCC).

Condition or Disease	Intervention/Treatment	Phase
Liver Cancer; Hepatocellular Cancer	Radiation: individualized Stereotactic Body Radiation Therapy (SBRT)	Phase 2

Detailed Description

The trial endpoints are toxicity, survival and progression-free survival. DCE-MRI and plasma biomarkers will also be collected to explore their use as tools for treatment individualization in future trials. During the current trial, an indicator of liver function, indocyanine green (ICG), will be used to identify during treatment patients who are at excess risk for radiation-induced liver disease (RILD) so that their radiation dose may be reduced. The model used for individualization will be updated as trial data accrue, so this is an adaptive trial of an individualized therapy. The planned accrual is seventy (70) evaluable patients over three years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 94 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Individualized Stereotactic Body Radiation Therapy (SBRT) for Intrahepatic Cancer
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Liver cancer patients The aim of this study is to determine the safety and effectiveness of individualized Stereotactic Body Radiation Therapy (SBRT) in patients who either (1) have had previous liver treatments, and/or (2) have primary hepatocellular carcinoma (HCC).

Radiation: individualized Stereotactic Body Radiation Therapy (SBRT); The individualized SBRT involves two treatment phases. The first phase of treatment involves receiving three fractions of SBRT, followed by a 1-month break and assessment of liver function with a blood test - Indocyanine Green (IC-Green). The second phase of treatment involves receiving two more fractions of SBRT, whose doses are adjusted to account for tolerance of the first phase of treatment.

Outcome Measures

Primary Outcome Measures

1. The Percentage of Patients With Local Control at 1 Year Post Treatment [1 Year]

   For this study, local control is defined as the lack of progressive local disease following CR (Complete Response) or PR (Partial Response), or lack of progressive local disease in patients with non-evaluable disease, who have no progressive elevation in serum tumor markers.

Secondary Outcome Measures

1. The Percentage of Patients Alive Without Progression at 1 Year [1 Year]

   Progression is defined as a greater than or equal to 20% growth of a lesion from the smallest lesion measurement

2. The Percentage of Patients Alive at 1 Year [1 Year]

3. The Number of Patients Who Experience Grade 4+ Hepatotoxicity [1 Year]

   Grade 4 toxicities are life threatening toxicities that require urgent attention.

4. The Number of Patients That Experience Grade 4+ Gastrointestinal Bleeding [1 Year]

   Grade 4 toxicities are life threatening toxicities that require urgent attention.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• over age 18

• life expectancy of at least 12 weeks

• Zubrod performance status of ≤2.

• biopsy proven hepatocellular carcinoma (HCC)

• liver metastases

• a discrete hepatic tumor(s) as defined by the Barcelona46 criteria - for cirrhotic patients, (1) 2 imaging studies showing hypervascular tumor > 2cm, or (2) single imaging study showing hypervascular tumor > 2cm with AFP ≥ 400 ng/mL

• a discrete hypervascular tumor present on two consecutive imaging studies (CT or MRI) with documented growth of > 1cm in diameter

• adequate organ function

• women and men not interested in pregnancy

• must be recovered from the effects of any prior surgery, radiation therapy, chemotherapy and the effects of Radiofrequency Ablation (RFA) or Transcatheter Arterial Chemo Embolization (TACE)

• minimum of 6 weeks following their last surgical procedure, radiation and chemotherapy.

Exclusion Criteria:

• cannot be eligible for a curative liver resection

• uncontrolled ascites clinically evident on physical exam

• known allergy to IC-Green

• known allergy to intravenous iodinated contrast agents

• patients with poor venous access

• patients with metastatic cancer with normal liver function who have not undergone previous liver directed therapy and a single tumor < 6 cm in size.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-5010

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Kyle Cuneo, MD, University of Michigan Rogel Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT01522937
• Other Study ID Numbers: UMCC 2009-053; HUM00029467
• First Posted: Feb 1, 2012
• Last Update Posted: Mar 9, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Liver Neoplasms; Carcinoma, Hepatocellular

Study Results

Participant Flow

Arm/Group Title	Liver Cancer Patients
Arm/Group Description	The aim of this study is to determine the safety and effectiveness of individualized Stereotactic Body Radiation Therapy (SBRT) in patients who either (1) have had previous liver treatments, and/or (2) have primary hepatocellular carcinoma (HCC). individualized Stereotactic Body Radiation Therapy (SBRT): The individualized SBRT involves two treatment phases. The first phase of treatment involves receiving three fractions of SBRT, followed by a 1-month break and assessment of liver function with a blood test - Indocyanine Green (IC-Green). The second phase of treatment involves receiving two more fractions of SBRT, whose doses are adjusted to account for tolerance of the first phase of treatment.
Period Title: Overall Study
STARTED	146
COMPLETED	146
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Liver Cancer Patients
Arm/Group Description	The aim of this study is to determine the safety and effectiveness of individualized Stereotactic Body Radiation Therapy (SBRT) in patients who either (1) have had previous liver treatments, and/or (2) have primary hepatocellular carcinoma (HCC). individualized Stereotactic Body Radiation Therapy (SBRT): The individualized SBRT involves two treatment phases. The first phase of treatment involves receiving three fractions of SBRT, followed by a 1-month break and assessment of liver function with a blood test - Indocyanine Green (IC-Green). The second phase of treatment involves receiving two more fractions of SBRT, whose doses are adjusted to account for tolerance of the first phase of treatment.
Overall Participants	146
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	65
Gender (Count of Participants)
Female	30 20.5%
Male	116 79.5%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Patients With Local Control at 1 Year Post Treatment
Description	For this study, local control is defined as the lack of progressive local disease following CR (Complete Response) or PR (Partial Response), or lack of progressive local disease in patients with non-evaluable disease, who have no progressive elevation in serum tumor markers.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liver Cancer Patients
Arm/Group Description	The aim of this study is to determine the safety and effectiveness of individualized Stereotactic Body Radiation Therapy (SBRT) in patients who either (1) have had previous liver treatments, and/or (2) have primary hepatocellular carcinoma (HCC). individualized Stereotactic Body Radiation Therapy (SBRT): The individualized SBRT involves two treatment phases. The first phase of treatment involves receiving three fractions of SBRT, followed by a 1-month break and assessment of liver function with a blood test - Indocyanine Green (IC-Green). The second phase of treatment involves receiving two more fractions of SBRT, whose doses are adjusted to account for tolerance of the first phase of treatment.
Measure Participants	102
Number (95% Confidence Interval) [percentage of patients]	99

2. Secondary Outcome

Title	The Percentage of Patients Alive Without Progression at 1 Year
Description	Progression is defined as a greater than or equal to 20% growth of a lesion from the smallest lesion measurement
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liver Cancer Patients
Arm/Group Description	The aim of this study is to determine the safety and effectiveness of individualized Stereotactic Body Radiation Therapy (SBRT) in patients who either (1) have had previous liver treatments, and/or (2) have primary hepatocellular carcinoma (HCC). individualized Stereotactic Body Radiation Therapy (SBRT): The individualized SBRT involves two treatment phases. The first phase of treatment involves receiving three fractions of SBRT, followed by a 1-month break and assessment of liver function with a blood test - Indocyanine Green (IC-Green). The second phase of treatment involves receiving two more fractions of SBRT, whose doses are adjusted to account for tolerance of the first phase of treatment.
Measure Participants	102
Number (95% Confidence Interval) [percentage of patients]	62

3. Secondary Outcome

Title	The Percentage of Patients Alive at 1 Year
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liver Cancer Patients
Arm/Group Description	The aim of this study is to determine the safety and effectiveness of individualized Stereotactic Body Radiation Therapy (SBRT) in patients who either (1) have had previous liver treatments, and/or (2) have primary hepatocellular carcinoma (HCC). individualized Stereotactic Body Radiation Therapy (SBRT): The individualized SBRT involves two treatment phases. The first phase of treatment involves receiving three fractions of SBRT, followed by a 1-month break and assessment of liver function with a blood test - Indocyanine Green (IC-Green). The second phase of treatment involves receiving two more fractions of SBRT, whose doses are adjusted to account for tolerance of the first phase of treatment.
Measure Participants	102
Number (95% Confidence Interval) [percentage of patients]	67

4. Secondary Outcome

Title	The Number of Patients Who Experience Grade 4+ Hepatotoxicity
Description	Grade 4 toxicities are life threatening toxicities that require urgent attention.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liver Cancer Patients
Arm/Group Description	The aim of this study is to determine the safety and effectiveness of individualized Stereotactic Body Radiation Therapy (SBRT) in patients who either (1) have had previous liver treatments, and/or (2) have primary hepatocellular carcinoma (HCC). individualized Stereotactic Body Radiation Therapy (SBRT): The individualized SBRT involves two treatment phases. The first phase of treatment involves receiving three fractions of SBRT, followed by a 1-month break and assessment of liver function with a blood test - Indocyanine Green (IC-Green). The second phase of treatment involves receiving two more fractions of SBRT, whose doses are adjusted to account for tolerance of the first phase of treatment.
Measure Participants	102
Number [patients]	0

5. Secondary Outcome

Title	The Number of Patients That Experience Grade 4+ Gastrointestinal Bleeding
Description	Grade 4 toxicities are life threatening toxicities that require urgent attention.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liver Cancer Patients
Arm/Group Description	The aim of this study is to determine the safety and effectiveness of individualized Stereotactic Body Radiation Therapy (SBRT) in patients who either (1) have had previous liver treatments, and/or (2) have primary hepatocellular carcinoma (HCC). individualized Stereotactic Body Radiation Therapy (SBRT): The individualized SBRT involves two treatment phases. The first phase of treatment involves receiving three fractions of SBRT, followed by a 1-month break and assessment of liver function with a blood test - Indocyanine Green (IC-Green). The second phase of treatment involves receiving two more fractions of SBRT, whose doses are adjusted to account for tolerance of the first phase of treatment.
Measure Participants	102
Number [patients]	0

Adverse Events

Arm/Group Title	Liver Cancer Patients
Arm/Group Description	The aim of this study is to determine the safety and effectiveness of individualized Stereotactic Body Radiation Therapy (SBRT) in patients who either (1) have had previous liver treatments, and/or (2) have primary hepatocellular carcinoma (HCC). individualized Stereotactic Body Radiation Therapy (SBRT): The individualized SBRT involves two treatment phases. The first phase of treatment involves receiving three fractions of SBRT, followed by a 1-month break and assessment of liver function with a blood test - Indocyanine Green (IC-Green). The second phase of treatment involves receiving two more fractions of SBRT, whose doses are adjusted to account for tolerance of the first phase of treatment.
All Cause Mortality
	Liver Cancer Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Liver Cancer Patients
	Affected / at Risk (%)	# Events
Total	22/146 (15.1%)
Blood and lymphatic system disorders
Anemia	1/146 (0.7%)	1
Cardiac disorders
Atrial fibrillation	1/146 (0.7%)	1
Chest pain - cardiac	1/146 (0.7%)	1
Heart failure	1/146 (0.7%)	1
Myocardial infarction	1/146 (0.7%)	1
Gastrointestinal disorders
Diarrhea	1/146 (0.7%)	1
Esophageal varices hemorrhage	1/146 (0.7%)	1
Pancreatitis	1/146 (0.7%)	1
Vomiting	1/146 (0.7%)	1
Abdominal pain	2/146 (1.4%)	2
Gastrointestinal disorders - Other	2/146 (1.4%)	2
Nausea	2/146 (1.4%)	2
Upper gastrointestinal hemorrhage	2/146 (1.4%)	3
Ascites	3/146 (2.1%)	3
General disorders
Chills	1/146 (0.7%)	1
Multi-organ failure	1/146 (0.7%)	1
Fatigue	2/146 (1.4%)	2
Fever	2/146 (1.4%)	2
Hepatobiliary disorders
Cholecystitis	1/146 (0.7%)	1
Hepatobiliary disorders - Other	3/146 (2.1%)	3
Infections and infestations
Sepsis	1/146 (0.7%)	1
Urinary tract infection	1/146 (0.7%)	1
Lung infection	2/146 (1.4%)	2
Injury, poisoning and procedural complications
Fall	1/146 (0.7%)	1
Investigations
Blood bilirubin increased	1/146 (0.7%)	1
Metabolism and nutrition disorders
Dehydration	1/146 (0.7%)	1
Hyperglycemia	1/146 (0.7%)	1
Metabolism and nutrition disorders - Other	1/146 (0.7%)	1
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	1/146 (0.7%)	1
Nervous system disorders
Encephalopathy	1/146 (0.7%)	1
Psychiatric disorders
Psychiatric disorders - Other	2/146 (1.4%)	2
Renal and urinary disorders
Renal and urinary disorders - Other	1/146 (0.7%)	1
Urinary retention	1/146 (0.7%)	1
Acute kidney injury	2/146 (1.4%)	2
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/146 (0.7%)	1
Pneumonitis	1/146 (0.7%)	1
Respiratory, thoracic and mediastinal disorders - Other	1/146 (0.7%)	2
Social circumstances
Social circumstances - Other	1/146 (0.7%)	1
Vascular disorders
Hypotension	1/146 (0.7%)	1
Thromboembolic event	2/146 (1.4%)	2
Other (Not Including Serious) Adverse Events
	Liver Cancer Patients
	Affected / at Risk (%)	# Events
Total	81/146 (55.5%)
Blood and lymphatic system disorders
Anemia	9/146 (6.2%)	10
Cardiac disorders
Sick sinus syndrome	1/146 (0.7%)	1
Sinus tachycardia	2/146 (1.4%)	2
Ear and labyrinth disorders
Ear and labyrinth disorders - Other	1/146 (0.7%)	1
Tinnitus	1/146 (0.7%)	1
Eye disorders
Blurred vision	1/146 (0.7%)	1
Gastrointestinal disorders
Abdominal distension	3/146 (2.1%)	3
Bloating	1/146 (0.7%)	1
Dyspepsia	4/146 (2.7%)	4
Esophagitis	1/146 (0.7%)	1
Gastritis	21/146 (14.4%)	22
Oral pain	1/146 (0.7%)	1
Diarrhea	2/146 (1.4%)	2
Vomiting	8/146 (5.5%)	11
Abdominal pain	3/146 (2.1%)	5
Gastrointestinal disorders - Other	2/146 (1.4%)	2
Nausea	7/146 (4.8%)	8
Ascites	9/146 (6.2%)	10
General disorders
Edema limbs	5/146 (3.4%)	6
General disorders and administration site conditions - Other	5/146 (3.4%)	5
Non-cardiac chest pain	1/146 (0.7%)	1
Pain	3/146 (2.1%)	3
Chills	1/146 (0.7%)	2
Fatigue	64/146 (43.8%)	94
Fever	1/146 (0.7%)	2
Hepatobiliary disorders
Hepatic failure	1/146 (0.7%)	1
Hepatic pain	33/146 (22.6%)	38
Portal vein thrombosis	1/146 (0.7%)	1
Infections and infestations
Urinary tract infection	1/146 (0.7%)	1
Investigations
Alanine aminotransferase increased	2/146 (1.4%)	2
Alkaline phosphatase increased	2/146 (1.4%)	2
Aspartate aminotransferase increased	2/146 (1.4%)	2
CD4 lymphocytes decreased	1/146 (0.7%)	1
Creatinine increased	1/146 (0.7%)	1
INR increased	1/146 (0.7%)	1
Lipase increased	1/146 (0.7%)	1
Lymphocyte count decreased	21/146 (14.4%)	24
Neutrophil count decreased	2/146 (1.4%)	2
Platelet count decreased	12/146 (8.2%)	18
Serum amylase increased	1/146 (0.7%)	1
White blood cell decreased	7/146 (4.8%)	12
Blood bilirubin increased	6/146 (4.1%)	10
Metabolism and nutrition disorders
Acidosis	1/146 (0.7%)	1
Anorexia	3/146 (2.1%)	4
Hyperkalemia	2/146 (1.4%)	5
Hypoalbuminemia	4/146 (2.7%)	5
Hypocalcemia	1/146 (0.7%)	1
Hypoglycemia	1/146 (0.7%)	1
Hyponatremia	3/146 (2.1%)	3
Dehydration	2/146 (1.4%)	2
Hyperglycemia	6/146 (4.1%)	8
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other	1/146 (0.7%)	4
Neck pain	1/146 (0.7%)	1
Pain in extremity	1/146 (0.7%)	1
Generalized muscle weakness	1/146 (0.7%)	1
Nervous system disorders
Ataxia	1/146 (0.7%)	1
Depressed level of consciousness	1/146 (0.7%)	1
Dizziness	2/146 (1.4%)	2
Dysarthria	1/146 (0.7%)	1
Dysgeusia	1/146 (0.7%)	1
Peripheral sensory neuropathy	1/146 (0.7%)	2
Seizure	1/146 (0.7%)	1
Syncope	1/146 (0.7%)	1
Encephalopathy	2/146 (1.4%)	3
Psychiatric disorders
Anxiety	2/146 (1.4%)	2
Confusion	3/146 (2.1%)	4
Depression	3/146 (2.1%)	3
Personality change	1/146 (0.7%)	1
Psychiatric disorders - Other	2/146 (1.4%)	2
Renal and urinary disorders
Hematuria	1/146 (0.7%)	1
Urine discoloration	2/146 (1.4%)	2
Renal and urinary disorders - Other	1/146 (0.7%)	1
Acute kidney injury	1/146 (0.7%)	1
Reproductive system and breast disorders
Erectile dysfunction	2/146 (1.4%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/146 (3.4%)	5
Epistaxis	4/146 (2.7%)	4
Hiccups	1/146 (0.7%)	1
Hoarseness	1/146 (0.7%)	1
Pleural effusion	1/146 (0.7%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/146 (0.7%)	1
Pruritus	1/146 (0.7%)	1
Skin and subcutaneous tissue disorders - Other	4/146 (2.7%)	4
Vascular disorders
Hypertension	2/146 (1.4%)	2
Thromboembolic event	1/146 (0.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.