Radiation Therapy With Sorafenib for TACE-Resistant Hepatocellular Carcinoma

NCT01618253 | Withdrawn Phase 1 DMC

• 1 other identifier: PRO00017344
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the maximum tolerated radiation dose with concurrent sorafenib for unresectable hepatocellular carcinoma that has not responded to transarterial chemoembolization.

Conditions

Hepatocellular Carcinoma; Hepatocellular Cancer; Hepatoma; Liver Cancer

Keywords

Transarterial Chemoembolization; TACE; Sorafenib Tosylate; Sorafenib; Nexavar; External Beam Radiation Therapy; Radiation Therapy; Radiotherapy; Radiation

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Maximum tolerated dose (MTD) will be determined by dose limiting toxicity (DLT) that is observed in either the acute (during treatment) or subacute (up to 3 months after treatment) setting. Acute DLT will be defined by grade 3-5 hepatic, gastrointestinal, dermatologic, hematologic, or pulmonary toxicity per Common Toxicity Criteria for Adverse Effects (CTCAE), v4.0. Subacute DLT will be defined by radiation induced liver disease (RILD) or grade 3-5 gastrointestinal, hematologic, or pulmonary toxicity per CTCAE, v4.0.

  From date of enrollment until 3 months after completion of treatment.

Secondary Outcomes (5)

• Radiographic Response

  1 & 3 months post-treatment.

• Patterns of Failure

  From date of enrollment until the date of first documented progression, last known folow-up, or date of death from any cause, whichever came first, assessed up to 10 years.

• Progression Free Survival

  From date of enrollment until the date of first documented progression, last known folow-up, or date of death from any cause, whichever came first, assessed up to 10 years.

• Overall Survival

  From date of enrollment until the date of last known folow-up or date of death from any cause, whichever came first, assessed up to 10 years.

• Health Related Quality of Life

  1, 2, & 3 months post-treatment.

Study Arms (1)

Radiation therapy with concurrent sorafenib

EXPERIMENTAL

Drug: Sorafenib; Radiation: Conventional fractionation (2 Gy per day) external beam radiation therapy

Interventions

Sorafenib DRUG

Sorafenib 400 mg PO bid will be started two weeks prior to initiation of radiation therapy (RT) and continue until the end of protocol specified radiation dose.

Also known as: Sorafenib Tosylate, Nexavar

Radiation therapy with concurrent sorafenib

Conventional fractionation (2 Gy per day) external beam radiation therapy RADIATION

Patients will be stratified by the maximum diameter of HCC in any plane (≤10 cm or \>10 cm) based on post-TACE, contrast enhanced MRI or CT. If only 1 lesion is present, the maximum diameter of that lesion in any plane determines stratification. If \>1 but ≤3 lesions are present, the sum of the maximum diameter in any plane of all the lesions determines stratification. The MTD will be determined utilizing a standard 3 + 3 dose escalation scheme (4 Gy increase per bin). For lesions ≤10 cm, the starting RT dose bin will be 42 Gy and escalate to a pre-determined maximum of 62 Gy if no DLT's are experienced. For lesions \>10 cm, the starting RT dose bin will be 40 Gy and escalate to a pre-determined maximum of 52 Gy if no DLT's are experienced.

Also known as: External Beam Radiation Therapy, Radiation Therapy, Radiotherapy

Radiation therapy with concurrent sorafenib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Radiographic or histologic diagnosis of hepatocellular carcinoma (HCC).
• Maximum of 3 HCC lesions within the liver.
• No evidence of lymphadenopathy or metastatic disease per either CT or PET.
• Prior transarterial chemo-embolization (TACE) at least 28 days prior to initiation of protocol therapy.
• Evidence of either progressive disease or stable disease following TACE.
• Child Pugh Class A (score 5-6) or B (score 7).
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 (or Karnofsky ≥70%).
• Normal organ and marrow function (platelets \>60,000/mc; hemoglobin ≥8.5 g/dL; international normalized ratio (INR) ≤2.3; albumin ≥2.8 g/dL; total bilirubin ≤3 mg/dL; aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \<5x upper limit of normal; creatinine ≤1.5x upper limit of normal).
• Negative human immunodeficiency virus serology.
• Negative pregnancy test for women of child bearing age.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Less than 800 cc of normal liver.
• Child Pugh Class B (score 8-9) or C (score 10-15).
• Acute/active hepatitis B infection.
• Prior systemic chemotherapy or abdominal radiation therapy.
• Portal venous (main, primary right, or primary left trunks) or inferior vena cava thrombosis.
• Prior malignancy within 5 years of enrollment except for non-melanoma skin cancer.
• Prior history of myocardial infarction, cerebrovascular accident, or esophageal variceal bleed in the last 6 months.
• Pre-existing heart failure with either a clinical classification of New York Heart Association Class III or IV or cardiac ejection fraction of \<45%.
• Systolic blood pressure \> 160 mmHg or diastolic pressure \> 100 mmHg despite optimal medical management.
• Pulmonary hemorrhage or other serious bleeding event (grade 2+) within 4 weeks initiation of protocol therapy.
• Prior history of scleroderma or active systemic lupus erythematosus.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (3)

• Chung YL, Jian JJ, Cheng SH, Tsai SY, Chuang VP, Soong T, Lin YM, Horng CF. Sublethal irradiation induces vascular endothelial growth factor and promotes growth of hepatoma cells: implications for radiotherapy of hepatocellular carcinoma. Clin Cancer Res. 2006 May 1;12(9):2706-15. doi: 10.1158/1078-0432.CCR-05-2721.

  PMID: 16675562 BACKGROUND

• Plastaras JP, Kim SH, Liu YY, Dicker DT, Dorsey JF, McDonough J, Cerniglia G, Rajendran RR, Gupta A, Rustgi AK, Diehl JA, Smith CD, Flaherty KT, El-Deiry WS. Cell cycle dependent and schedule-dependent antitumor effects of sorafenib combined with radiation. Cancer Res. 2007 Oct 1;67(19):9443-54. doi: 10.1158/0008-5472.CAN-07-1473.

  PMID: 17909054 BACKGROUND

• Ren ZG, Zhao JD, Gu K, Chen Z, Lin JH, Xu ZY, Hu WG, Zhou ZH, Liu LM, Jiang GL. Three-dimensional conformal radiation therapy and intensity-modulated radiation therapy combined with transcatheter arterial chemoembolization for locally advanced hepatocellular carcinoma: an irradiation dose escalation study. Int J Radiat Oncol Biol Phys. 2011 Feb 1;79(2):496-502. doi: 10.1016/j.ijrobp.2009.10.070. Epub 2010 Apr 24.

  PMID: 20421145 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Sorafenib; Radiotherapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Therapeutics

Study Officials

• Beth A. Erickson-Wittmann, M.D.

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2012
• First Posted: June 13, 2012
• Study Start: June 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2016
• Last Updated: September 5, 2013

Record last verified: 2013-09

Locations

US (1)