Phase 3 Study of ThermoDox With Radiofrequency Ablation (RFA) in Treatment of Hepatocellular Carcinoma (HCC)

NCT00617981 | Completed Phase 3 Results DMC

• 1 other identifier: 104-06-301
• Study Type: interventional
• Target: 701
• Locations: 11 countries
• Sites: 79

Brief Summary

The purpose of this study is to determine whether ThermoDox, a thermally sensitive liposomal doxorubicin, is effective in the treatment of non-resectable hepatocellular carcinoma when used in conjunction with radiofrequency ablation (RFA).

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; liver cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival Will be Measured From the Date of Randomization to the First Date on Which One of the Following Occurs. o Local Recurrence o Any New Distant Intrahepatic HCC Tumor o Any New Extrahepatic HCC Tumor o Death From Any Cause

  3 years

Secondary Outcomes (4)

• Overall Survival as Measured by Time From Randomization to Death or the End of the Study.

  3 years

• Number of Participants With Definite Worsening as Per Patient-Reported Outcomes

  3 years

• Number of Participants With Local Recurrence

  3 years

• Evaluation of Safety

  3 years

Study Arms (2)

ThermoDox + RFA

EXPERIMENTAL

ThermoDox 50 mg/m2 start infusion over 30 minutes about 15 minutes before radiofrequency ablation begins.

Drug: ThermoDox

Sham + RFA

SHAM COMPARATOR

Sham infusion over 30 minutes about 15 minutes before radiofrequency ablation begins.

Drug: 5% Dextrose Solution

Interventions

ThermoDox DRUG

Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion

ThermoDox + RFA

5% Dextrose Solution DRUG

Single 30 minute intravenous infusion

Sham + RFA

Eligibility Criteria

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

You may qualify if:

• Diagnosed hepatocellular carcinoma (HCC)
• No more than 4 HCC lesions with at least one ≥ 3.0 cm and none \> 7.0 cm in maximum diameter, based on diagnosis at screening.
• If a subject has a large lesion (5.0 - 7.0 cm), any other lesions must be less than 5.0 cm.
• Anticipated ablation volume will be no larger than either removal of 3 hepatic segments or removal of more than 30% of total liver volume (as per maximum surgical limit).
• If additional lesions are discovered during the laparoscopic or open treatment procedure, that were undetectable by CT at screening, the size and location of the lesion(s) will be recorded in the CRF and the lesions will be treated at the discretion of the physician and guided by the local standard of care. The subject will remain on study if all lesions are treated. If any lesions cannot be completely ablated within two treatment attempts the subject will be considered a treatment failure.
• Study subjects being considered for re-treatment after disease progression may have more than 4 lesions.
• Male or female 18 years of age or older.
• Are willing to sign an informed consent form, indicating that they are aware of the investigational nature of this study that is in keeping with the policies of the institution.
• Be an appropriate candidate for receiving RFA as a medically indicated treatment as evaluated by the following factors:
• Number of lesions
• Size of lesions
• Overall health of liver
• Not a candidate for surgical resection
• Have an echocardiogram revealing a Left Ventricular Ejection Fraction (LVEF) ≥ 50%. Measurements with a multiple gated acquisition (MUGA) scan are allowed if an echocardiogram cannot be performed. The same method of measurement should be used to evaluate ejection fraction (EF) of the subject for the duration of the study.
• Willing to return to the study site for their study visits.

You may not qualify if:

• Have serious medical illnesses including, but not limited to, congestive heart failure, myocardial infarction or cerebral vascular accident within the last six months, or life threatening cardiac arrhythmias.
• Is scheduled for liver transplantation.
• Have previously received any treatment for HCC (except for study subjects being considered for completion of treatment or re-treatment).
• Have previously received any doxorubicin (study subjects being considered for completion of treatment or re-treatment may have received ThermoDox previously).
• Have extrahepatic metastasis.
• Are pregnant or breast-feeding. In women of childbearing potential, a negative pregnancy test (serum) is required prior to study treatment.
• Women of childbearing potential who are not practicing an acceptable form of birth control (i.e. diaphragm, cervical cap, condom, surgical sterility or birth control pills. Women whose partner has undergone a vasectomy must use a second form of birth control).
• Have any known allergic reactions to any of the drugs or liposomal components or intravenous imaging agents to be used in this study.
• Have portal or hepatic vein tumor invasion/thrombosis.
• Have INR \> 1.5 times the institution's upper normal limit (UNL), except in subjects who are therapeutically anticoagulated for medical conditions unrelated to HCC such as atrial fibrillation. Subjects may be re-screened after condition is treated or anticoagulant is withheld.
• Have platelet count \< 75,000/mm3, absolute neutrophil count \< 1500/mm3, or Hgb \< 10.0 g/dL (unless the hemoglobin value has been stable, the subject is cardiovascularly stable, asymptomatic and judged able to withstand the RFA procedure).
• Have serum creatinine ≥ 2.5 mg/dL or calculated creatinine clearance (CrCl) ≤ 25.0 mL/min.
• Have serum bilirubin \> 3.0 mg/dL.
• Have serum albumin \< 2.8 g/dL.
• Have body temperature \>1010F (38.30C) immediately prior to study treatment.

Sponsors & Collaborators

• Imunon: lead

Study Sites (79)

UCLA

Los Angeles, California, 90095, United States

Location

Mayo Clinic - Jacksonville, Florida

Jacksonville, Florida, 32224, United States

Location

University Of Louisville

Louisville, Kentucky, 40202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Geisinger Health System

Wilkes-Barre, Pennsylvania, 18711, United States

Location

University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2L4, Canada

Location

The 1st Affiliated Hospital, Fujian Medical University

Fuzhou, Fujian, 350005, China

Location

Tongji Hospital

Wuhan, Hubei, 430030, China

Location

Nanjing Drum Tower Hospital, The Affilitated Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

Location

The First Affiliated Hospital of Suzhou University

Suzhou, Jiangsu, 215006, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310013, China

Location

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, 100021, China

Location

Beijing Cancer Hospital, Peking University School of Oncology

Beijing, 100036, China

Location

Beijing You An Hospital, Capital Medical University

Beijing, 100069, China

Location

Beijing You An Hospital，Capital Medical University

Beijing, 100069, China

Location

Southwest Hospital, The First Affiliated Hospital of the Third Military Medical University

Chongqing, 400038, China

Location

Sun Yat-Sen University Cancer Center

Guangzhou, 510060, China

Location

Oncology Center of Nanfang Hospital, Southern Medical University

Guangzhou, 510515, China

Location

Shanghai Changhai Hospital, Second Military Medical University

Shanghai, 200433, China

Location

Tianjin No. 3 Central Hospital

Tianjin, 300170, China

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Azienda Ospedaliera di Padova

Padua, Veneto, 35128, Italy

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola Malpighi

Bologna, 40138, Italy

Location

Ospedale Classificato San Giuseppe, Milano

Milan, 20123, Italy

Location

Azienda Ospedaliera San Gerardo

Monza, 20052, Italy

Location

Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Pascale" di Napoli

Napoli, 80131, Italy

Location

Azienda Ospedaliero-Univeristaria Pisana

Pisa, 56124, Italy

Location

Istituto dei Tumori Regina Elena

Roma, 00144, Italy

Location

Azienda Sanitaria Ospedaliera Ordine Mauriziano di Torino Presidio Ospedaliero "Umberto I"

Torino, 10128, Italy

Location

Chiba University Hospital

Chiba, 260-8677, Japan

Location

Yamanashi Prefectural Central Hospital

Kofu, 400-8506, Japan

Location

Mie University Hospital

Mie, 514-8507, Japan

Location

Saiseikai Niigata Daini Hospital

Niigata, 950-1104, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Iwate Medical University Hospital

Shiwa, 020-8505, Japan

Location

Kyoundo Hospital

Tokyo, 101-0062, Japan

Location

The University of Tokyo Hospital

Tokyo, 113-8655, Japan

Location

Japanese Red Cross Medical Center

Tokyo, 150-8935, Japan

Location

JR Tokyo General Hospital

Tokyo, 151-8528, Japan

Location

Kanto Central Hospital

Tokyo, 158-8531, Japan

Location

Wakayama Medical University

Wakayama, 641-8510, Japan

Location

Yokohama City University Medical Center

Yokohama, 232-0024, Japan

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Chinese General Hospital and Medical Center

Santa Cruz, Manila, 1003, Philippines

Location

The Medical City

Pasig, National Capital Region, 1605, Philippines

Location

St. Luke's Medical Center

Quezon City, 1112, Philippines

Location

Cardinal Santos Medical Center

San Juan City, 1053, Philippines

Location

Soonchunhyang University Bucheon Hospital

Gyeonggi-do, Bucheon-si, South Korea

Location

Samsung Medical Center

Seoul, Gangnam-gu, 135-710, South Korea

Location

Inje University Ilsan Paik Hospital

Gyeonggi-do, Goyang-si, 411-706, South Korea

Location

Kyungpook National University Hospital

Daegu, Gyeongsangbuk-do, 700-721, South Korea

Location

Seoul National University Hospital

Seoul, Jongno-gu, 110-744, South Korea

Location

Kyungpook National University Hospital

Daegu, Jung-gu, 700-721, South Korea

Location

The Catholic University of Korea, Kangnam St.Mary's Hospital

Seoul, Seocho-gu, 137-701, South Korea

Location

Pusan National University Hospital

Busan, 602-739, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 464-707, South Korea

Location

Yonsei University Severance Hospital

Seoul, 120-752, South Korea

Location

Korea University Medical Center Anam Hospital

Seoul, 136-705, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Chang Gung Memorial Hospital - Kao Shiung

Niaosong, Kaohsiung County, 833, Taiwan

Location

Chang Gung Memorial Hospital - Linkou

Linkou District, Taoyuan, 333, Taiwan

Location

Chang-Gung Memorial Hospital - Chiayi Branch

Chiayi City, 613, Taiwan

Location

Chang Gung Memorial Hospital - Keelung

Keelung, 204, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Tri-Service General Hospital

Taipei, 114, Taiwan

Location

Songklanagarind Hospital

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Thammasat University Hospital

Pathum Thani, 12120, Thailand

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

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

Results Point of Contact

• Title: Nicholas Borys, M.D. Senior Vice President and Chief Medical Officer
• Organization: Celsion Corporation

nborys@celsion.com

609-896-9100

Study Officials

• Ronnie T Poon, M.D.

  Queen Mary Hospital, University of Hong Kong

  STUDY DIRECTOR

• Riccardo Lencioni, M.D.

  University of Pisa

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2008
• First Posted: February 18, 2008
• Study Start: May 1, 2008
• Primary Completion: January 1, 2013
• Study Completion: August 1, 2016
• Last Updated: May 3, 2024
• Results First Posted: March 24, 2017

Record last verified: 2024-05

Locations

US (9); CA (2); CN (16); IT (8); HK (1); MY (1); TW (9); PH (4); TH (4); KR (12); JP (13)