Clinical trial NCT00243841: Dose Escalation Study for Primary Hepatocellular Carcinoma
Official title: Multi-institution Phase I/II Dose Escalation Study of Hypofractionated Stereotactic Body Radiation Therapy for Primary Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: University of Colorado, Denver
First posted: 2005-10-25
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the maximum tolerated dose of limited fractions of large dose radiation in an effort to achieve a biologically potent cancer therapy in selected patients with primary hepatocellular carcinoma.

Detailed description: Despite recent advances in early detection and diagnosis, only 30-40% of patients with hepatocellular carcinoma may benefit from radical therapies. Liver transplantation offers the best chance for cure. Surgical resection has been the only other potentially curative option, but the majority of patients are not candidates for resection. This reflects the usual comorbidity of severe underlying liver disease that either precludes surgery or makes the surgical approach extremely dangerous.

Eligibility criteria: Inclusion Criteria:

Evaluation by the Surgery and/or Liver Transplant Team has been performed and the patient is not considered a candidate for either "standard" therapy to target area (upper abdomen)

* Adequate liver function defined as:

  * total bilirubin \< 3mg/dl, albumin \> 2.5 g/dl
  * normal PT/PTT unless on anticoagulants
  * mild elevation of liver enzymes acceptable (must be less than three times upper limit of normal)
* Adequate renal function (creatinine \< 1.8 mg/dl or creatinine clearance ≥ 50 ml/min)
* Adequate bone marrow reserve:

  * ANC count ≥ 1500 mm3
  * Platelets ≥ 50,000/mm3
  * Hemoglobin \> 9 g/dL

NOTE: Lab values must be obtained within 2 weeks prior to being registered for protocol therapy.

Exclusion Criteria:

* No history of systemic lupus erythematous, rheumatoid arthritis, systemic sclerosis or scleroderma
* No chemotherapy within 14 days before radiotherapy (chemotherapy may cause transient hepatitis with hepatomegaly)
* No subsequent chemotherapy planned within 2 weeks of radiotherapy
* No active liver infection
* No acute Hepatitis. Definition of active disease:

  * Hepatitis A: Acute hepatitis determined by presence of Anti-HAV- IgM
  * Hepatitis B:

    1. HBsAg (HB surface Antigen): present in patients with acute and chronic hepatitis
    2. HBV DNA present in patients with active viral replication in amounts greater than 100,000 copies
    3. HBeAg is present in wild type HBV infection and suggests active replication
    4. Anti-HBs: Antibody against HBsAg appears after HBV infections and confers immunity
    5. Anti-HBc-IgM: Antibody against HBcAg, fraction IgM, present in acute infection and often could be detected during periods of high viral replication in chronic disease
    6. Anti-HBc-IgG: is present in chronic disease

Primary outcomes:
measure: Number of Patients With DLTs
timeFrame: 6 weeks
measure: 6 Month Local In-field Control
timeFrame: 6 months
Secondary outcomes:
measure: Time to In-field Failure
timeFrame: up to 4 yrs
measure: Overall Survival
timeFrame: Up to 8 years
measure: Phase II: Number of Patients With Treatment Related Grade 3 or 4 Adverse Events
timeFrame: up to 4 years
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Department of Radiation Oncology
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine
name: Mark Langer, MD
role: PRINCIPAL_INVESTIGATOR
References: