Study on Effectiveness and Safety of Hepatocellular Carcinoma Patients Treated With CyberKnife

NCT02363218 | Unknown Phase 2 DMC

• 1 other identifier: Ping Wang
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

Brief Summary

Study Phase: multi-institutional Phase II study Primary Objective(s): To determine overall survival for HCC patients treated with CyberKnife SBRT at 2 years. Secondary Objective(s): 1) To determine overall survival for HCC patients treated with CyberKnife SBRT at 1 year 2) To determine local control using RECIST and EASL criteria at 1 and 2 years 3) To assess progression-free survival at 1 and 2 years 4) To assess acute and late toxicities following CyberKnife SBRT. Hypothesis: Overall survival rate of HCC patients at one year after SBRT treatment is not less than 65%. Study Design: Single arm study. Patients will undergo a CT scan with and without contrast and MRI scan for radiation treatment planning and target delineation.SBRT will be delivered on the CyberKnife with Synchrony Respiratory Tracking capabilities. The tumor will be tracked with 3 implanted fiducial seeds for targeting. Treatment will be delivered in 3 fractions within a 7 day window at the discretion of the investigator. Sample size: The sample size required is 93 with a power of 90%, p=0.05, 50% response rate is considered not effective (p0) and 65% overall survival rate at 1 year (p1) is considered effectiveness of the treatment. The estimated drop-out rate is 20%, so the total sample size would be 117. Statistical Considerations: The set of Intention-To-Treat (ITT) will be analyzed. All patients will be censored at their last visit, including the patients lost to follow-up. All patients will be followed and counted in the therapy to which they were assigned, even if they decline that therapy. Only those patients who refuse (in writing) to have their outcomes count in the study's conclusions will not be included in the analyses from that time forward; however, the follow-up data for such patients will be included up until the time they withdraw consent. Such patients will be replaced. Baseline characteristics of patients will be presented with summary statistics. Time-to-event survival rates for OS and DFS will be estimated using the Kaplan-Meier method and presented at one and/or two years. The incidence of acute and late toxicities will be presented in tabular form on both a per-patient and per-event basis.

Conditions

Liver Neoplasms

Keywords

Liver Neoplasms; Stereotactic Body Radiotherapy; CyberKnife

Outcome Measures

Primary Outcomes (1)

• Overall survival rate

  Two years

Secondary Outcomes (3)

• Overall survival rate

  One year

• Local Control rate

  Two years

• Progression-free survival

  One-Two Years

Study Arms (1)

CyberKnife

EXPERIMENTAL

Hepatocellular Carcinoma Patients Treated With CyberKnife

Radiation: CyberKnife

Interventions

CyberKnife RADIATION

Patients will undergo a CT scan with and without contrast and MRI scan for radiation treatment planning and target delineation.SBRT will be delivered on the CyberKnife with Synchrony Respiratory Tracking capabilities. The tumor will be tracked with 3 implanted fiducial seeds for targeting. Treatment will be delivered in 3 fractions within a 7 day window at the discretion of the investigator.

CyberKnife

Eligibility Criteria

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

You may qualify if:

• Confirmed hepatocellular carcinoma according to one of three EASL criteria:
• Histopathology
• Two radiographic techniques (out of US, MRI, CT, Angiography) that confirm a lesion \>2 cm with arterial hypervascularization
• One radiographic technique that confirms a lesion \>2 cm with arterial hypervascularization and an AFP\>400 ng/mL
• Unifocal liver tumors not to exceed 5 cm in greatest axial dimension. Multifocal lesions will be restricted to a maximum of 3 lesions with a maximum lesion size of 3 cm for each lesion, that can be treated within a single target volume within the same liver segment as long as the dose constraints to normal tissue can be met.
• Volumn of uninvolved liver \>750 cc
• Hepatic lesion in patients for whom surgical resection is not possible or patients who refuse surgery.
• Eastern Clinical Oncology Group (ECOG) performance status 0, 1 or 2 (Appendix I)
• Patients with liver disease classified as Child Pugh class A
• Life expectancy \>6 months
• Age \> 18 years old
• Albumin \> 2.5 g/dL
• Total Bilirubin \< 3 mg/dL
• INR \<1.5
• Transaminases (SGOT and SGPT) no more than 3 times the upper limit of normal

You may not qualify if:

• Prior surgery, chemotherapy or radiation for the liver tumor
• Prior radiotherapy to the upper abdomen
• Prior RFA or liver transplant
• Tumors greater than 5 cm in greatest axial dimension
• Child B status
• Contraindication to receiving radiotherapy
• Active gastrointestinal bleed within 2 weeks of study enrollment
• Clinically significant ascites refractory to medical therapy
• Women who are pregnant
• Administration of any systemic chemotherapy within the last 6 months
• Presence of multifocal lesions located in different lobes of the liver or extrahepatic metastases
• Portal vein thrombus
• Participation in another concurrent treatment protocol

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Related Publications (16)

• Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005 Nov;42(5):1208-36. doi: 10.1002/hep.20933. No abstract available.

  PMID: 16250051 BACKGROUND

• Bruix J, Hessheimer AJ, Forner A, Boix L, Vilana R, Llovet JM. New aspects of diagnosis and therapy of hepatocellular carcinoma. Oncogene. 2006 Jun 26;25(27):3848-56. doi: 10.1038/sj.onc.1209548.

  PMID: 16799626 BACKGROUND

• Blomgren H, Lax I, Naslund I, Svanstrom R. Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. Acta Oncol. 1995;34(6):861-70. doi: 10.3109/02841869509127197.

  PMID: 7576756 BACKGROUND

• Cardenes HR, Price TR, Perkins SM, Maluccio M, Kwo P, Breen TE, Henderson MA, Schefter TE, Tudor K, Deluca J, Johnstone PA. Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma. Clin Transl Oncol. 2010 Mar;12(3):218-25. doi: 10.1007/s12094-010-0492-x.

  PMID: 20231127 BACKGROUND

• Fuss M, Salter BJ, Herman TS, Thomas CR Jr. External beam radiation therapy for hepatocellular carcinoma: potential of intensity-modulated and image-guided radiation therapy. Gastroenterology. 2004 Nov;127(5 Suppl 1):S206-17. doi: 10.1053/j.gastro.2004.09.035.

  PMID: 15508086 BACKGROUND

• Herfarth KK, Hof H, Bahner ML, Lohr F, Hoss A, van Kaick G, Wannenmacher M, Debus J. Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors. Int J Radiat Oncol Biol Phys. 2003 Oct 1;57(2):444-51. doi: 10.1016/s0360-3016(03)00586-8.

  PMID: 12957256 BACKGROUND

• Herfarth KK, Debus J, Lohr F, Bahner ML, Rhein B, Fritz P, Hoss A, Schlegel W, Wannenmacher MF. Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial. J Clin Oncol. 2001 Jan 1;19(1):164-70. doi: 10.1200/JCO.2001.19.1.164.

  PMID: 11134209 BACKGROUND

• Katz AW, Carey-Sampson M, Muhs AG, Milano MT, Schell MC, Okunieff P. Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases. Int J Radiat Oncol Biol Phys. 2007 Mar 1;67(3):793-8. doi: 10.1016/j.ijrobp.2006.10.025. Epub 2006 Dec 29.

  PMID: 17197128 BACKGROUND

• Kavanagh BD, Scheftera TE, Wersall PJ. Liver, renal, and retroperitoneal tumors: stereotactic radiotherapy. Front Radiat Ther Oncol. 2007;40:415-426. doi: 10.1159/000106051.

  PMID: 17641524 BACKGROUND

• Lax I, Blomgren H, Naslund I, Svanstrom R. Stereotactic radiotherapy of malignancies in the abdomen. Methodological aspects. Acta Oncol. 1994;33(6):677-83. doi: 10.3109/02841869409121782.

  PMID: 7946448 BACKGROUND

• Mendez Romero A, Wunderink W, Hussain SM, De Pooter JA, Heijmen BJ, Nowak PC, Nuyttens JJ, Brandwijk RP, Verhoef C, Ijzermans JN, Levendag PC. Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution phase i-ii study. Acta Oncol. 2006;45(7):831-7. doi: 10.1080/02841860600897934.

  PMID: 16982547 BACKGROUND

• Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001 Oct 15;94(2):153-6. doi: 10.1002/ijc.1440. No abstract available.

  PMID: 11668491 BACKGROUND

• Schefter TE, Kavanagh BD, Timmerman RD, Cardenes HR, Baron A, Gaspar LE. A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases. Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1371-8. doi: 10.1016/j.ijrobp.2005.01.002.

  PMID: 16029795 BACKGROUND

• Takeda A, Takahashi M, Kunieda E, Takeda T, Sanuki N, Koike Y, Atsukawa K, Ohashi T, Saito H, Shigematsu N, Kubo A. Hypofractionated stereotactic radiotherapy with and without transarterial chemoembolization for small hepatocellular carcinoma not eligible for other ablation therapies: Preliminary results for efficacy and toxicity. Hepatol Res. 2008 Jan;38(1):60-9. doi: 10.1111/j.1872-034X.2007.00084.x. Epub 2007 May 15.

  PMID: 17506837 BACKGROUND

• Tse RV, Hawkins M, Lockwood G, Kim JJ, Cummings B, Knox J, Sherman M, Dawson LA. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2008 Feb 1;26(4):657-64. doi: 10.1200/JCO.2007.14.3529. Epub 2008 Jan 2.

  PMID: 18172187 BACKGROUND

• Wada H, Takai Y, Nemoto K, Yamada S. Univariate analysis of factors correlated with tumor control probability of three-dimensional conformal hypofractionated high-dose radiotherapy for small pulmonary or hepatic tumors. Int J Radiat Oncol Biol Phys. 2004 Mar 15;58(4):1114-20. doi: 10.1016/j.ijrobp.2003.08.012.

  PMID: 15001252 BACKGROUND

MeSH Terms

Conditions

Liver Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• PING WANG, MD.PHD

  Tianjin Medical University Institute & Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

YONGCHUN SONG, MD

CONTACT

8613512208919; sych1977@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2015
• First Posted: February 13, 2015
• Study Start: May 1, 2014
• Primary Completion: May 1, 2017
• Study Completion: December 1, 2017
• Last Updated: October 7, 2016

Record last verified: 2015-02

Locations

CN (1)