Clinical trial · Interventional

Radiation Therapy With Sorafenib for TACE-Resistant Hepatocellular Carcinoma

Phase I Study of Radiation Therapy With Concurrent Sorafenib for Hepatocellular Carcinoma Not Responding to Transarterial Chemoembolization

NCT01618253CI-TRIAL-00012014withdrawnPhase 1ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Why stopped (as posted): Closed due to poor accrual.

Summary

Brief summary (as posted)

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

Conditions

Conditions (4)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Hepatocellular Cancer	Hepatocellular Carcinoma	CURATED_BROADER	0.80
Hepatocellular Carcinoma	Hepatocellular Carcinoma	ONTOLOGY_EXACT	0.98
Hepatoma	Hepatocellular Carcinoma	ALIAS	0.90
Liver Cancer	Malignant Liver Neoplasm	CURATED_EXACT	0.92

Interventions

Interventions (2)

Intervention	Type	Mapped drug	Match
Conventional fractionation (2 Gy per day) external beam radiation therapy	Radiation	—	UNRESOLVED
Sorafenib	Drug	Sorafenib	ALIAS

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Radiation therapy with concurrent sorafenib
interventionNames
1. Drug: Sorafenib
2. Radiation: Conventional fractionation (2 Gy per day) external beam radiation therapy

Primary outcomes (1)

measure
Maximum Tolerated Dose
timeFrame
From date of enrollment until 3 months after completion of treatment.
description
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.

Secondary outcomes (5)

measure

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years
Maximum age: 80 Years

Show eligibility criteria text

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

References

Publications (3)

BACKGROUNDChung 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
BACKGROUNDPlastaras 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
BACKGROUNDRen 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

Registry

Dates and enrollment

Start: Jun 1, 2012
Primary completion: Jun 1, 2015
Completion: Jun 1, 2016
First posted: Jun 13, 2012
Last update posted: Sep 5, 2013
Enrollment: 0 (actual)
Lead sponsor: Medical College of Wisconsin OTHER
Keywords: Transarterial Chemoembolization, TACE, Sorafenib Tosylate, Sorafenib, Nexavar, External Beam Radiation Therapy, Radiation Therapy, Radiotherapy, Radiation

Data updated 22 days agoSource updated Sep 5, 2013source: clinicaltrials

Locations

Locations by country (1)

Country	Sites	Recruiting
United States	1	0

Trial listing is informational. Eligibility is decided by the study team; contact information is on ClinicalTrials.gov.