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Hepatocellular CarcinomaPhase 3NCT00617981

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

A Phase 3 study testing ThermoDox and 5% Dextrose Solution in people with Hepatocellular Carcinoma, run by Imunon at 79 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
ThermoDox and 5% Dextrose Solution
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
701 participants
Where
79 sitesin 11 countries
Study dates
May 2008to Aug 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Have life expectancy of ≥ 4 months.
  • Have Child-Pugh Class A or B liver disease without encephalopathy or/and ascites.

Who cannot join

  • 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.
Show all 23Show fewer
  • 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.
  • Have contraindications to receiving doxorubicin HCl.
  • Are being treated with other investigational agents.
  • Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication (study subjects being considered for completion of treatment or re-treatment may have received ThermoDox previously).
  • Have other concurrent malignancy (subjects with treated squamous cell carcinoma of the skin or basal cell carcinoma of the skin may be included), evidence of extrahepatic cancer from their primary malignancy, or ongoing, medically significant active infection.
  • Documented HIV positive.
  • NYHA class III or IV functional classification for heart failure.
  • Evidence of hemachromatosis.
  • Have history of contrast-induced nephropathy.

Trial locations and contacts

79 sites in 11 countries.

79 sites in 11 countries

China16 sites

  • Cancer Institute and Hospital, Chinese Academy of Medical Sciences

    Beijing, 100021

  • Beijing Cancer Hospital, Peking University School of Oncology

    Beijing, 100036

  • Beijing You An Hospital, Capital Medical University

    Beijing, 100069

  • Beijing You An Hospital，Capital Medical University

    Beijing, 100069

  • The First Hospital of Jilin University

    Changchun, Jilin, 130021

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

    Chongqing, 400038

  • The 1st Affiliated Hospital, Fujian Medical University

    Fuzhou, Fujian, 350005

  • Sun Yat-Sen University Cancer Center

    Guangzhou, 510060

  • Oncology Center of Nanfang Hospital, Southern Medical University

    Guangzhou, 510515

  • The First Affiliated Hospital of Zhejiang University

    Hangzhou, Zhejiang, 310013

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

    Nanjing, Jiangsu, 210008

  • Shanghai Changhai Hospital, Second Military Medical University

    Shanghai, 200433

  • The First Affiliated Hospital of Suzhou University

    Suzhou, Jiangsu, 215006

  • Tianjin Cancer Hospital

    Tianjin, Tianjin Municipality, 300060

  • Tianjin No. 3 Central Hospital

    Tianjin, 300170

  • Tongji Hospital

    Wuhan, Hubei, 430030

Other trials in China

Japan13 sites

  • Chiba University Hospital

    Chiba, 260-8677

  • Yamanashi Prefectural Central Hospital

    Kofu, 400-8506

  • Mie University Hospital

    Mie, 514-8507

  • Saiseikai Niigata Daini Hospital

    Niigata, 950-1104

  • Okayama University Hospital

    Okayama, 700-8558

  • Iwate Medical University Hospital

    Shiwa, 020-8505

  • Kyoundo Hospital

    Tokyo, 101-0062

  • The University of Tokyo Hospital

    Tokyo, 113-8655

  • Japanese Red Cross Medical Center

    Tokyo, 150-8935

  • JR Tokyo General Hospital

    Tokyo, 151-8528

  • Kanto Central Hospital

    Tokyo, 158-8531

  • Wakayama Medical University

    Wakayama, 641-8510

  • Yokohama City University Medical Center

    Yokohama, 232-0024

Other trials in Japan

South Korea12 sites

  • Pusan National University Hospital

    Busan, 602-739

  • Kyungpook National University Hospital

    Daegu, Gyeongsangbuk-do, 700-721

  • Kyungpook National University Hospital

    Daegu, Jung-gu, 700-721

  • Soonchunhyang University Bucheon Hospital

    Gyeonggi-do, Bucheon-si

  • Inje University Ilsan Paik Hospital

    Gyeonggi-do, Goyang-si, 411-706

  • Seoul National University Bundang Hospital

    Seongnam-si, 464-707

  • Samsung Medical Center

    Seoul, Gangnam-gu, 135-710

  • Seoul National University Hospital

    Seoul, Jongno-gu, 110-744

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

    Seoul, Seocho-gu, 137-701

  • Yonsei University Severance Hospital

    Seoul, 120-752

  • Korea University Medical Center Anam Hospital

    Seoul, 136-705

  • Asan Medical Center

    Seoul, 138-736

Other trials in South Korea

United States9 sites

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Mayo Clinic - Jacksonville, Florida

    Jacksonville, Florida, 32224

  • UCLA

    Los Angeles, California, 90095

  • University Of Louisville

    Louisville, Kentucky, 40202

  • Mount Sinai School of Medicine

    New York, New York, 10029

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Texas Health Science Center

    San Antonio, Texas, 78229

  • Geisinger Health System

    Wilkes-Barre, Pennsylvania, 18711

Other trials in United States

Taiwan9 sites

  • Chang-Gung Memorial Hospital - Chiayi Branch

    Chiayi City, 613

  • Chang Gung Memorial Hospital - Keelung

    Keelung, 204

  • Chang Gung Memorial Hospital - Linkou

    Linkou District, Taoyuan, 333

  • Chang Gung Memorial Hospital - Kao Shiung

    Niaosong, Kaohsiung County, 833

  • China Medical University Hospital

    Taichung, 404

  • Taichung Veterans General Hospital

    Taichung, 407

  • National Taiwan University Hospital

    Taipei, 100

  • Taipei Veterans General Hospital

    Taipei, 112

  • Tri-Service General Hospital

    Taipei, 114

Other trials in Taiwan

Italy8 sites

  • Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola Malpighi

    Bologna, 40138

  • Ospedale Classificato San Giuseppe, Milano

    Milan, 20123

  • Azienda Ospedaliera San Gerardo

    Monza, 20052

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

    Naples, 80131

  • Azienda Ospedaliera di Padova

    Padova, Veneto, 35128

  • Azienda Ospedaliero-Univeristaria Pisana

    Pisa, 56124

  • Istituto dei Tumori Regina Elena

    Roma, 00144

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

    Torino, 10128

Other trials in Italy

Philippines4 sites

  • The Medical City

    Pasig, National Capital Region, 1605

  • St. Luke's Medical Center

    Quezon City, 1112

  • Cardinal Santos Medical Center

    San Juan City, 1053

  • Chinese General Hospital and Medical Center

    Santa Cruz, Manila, 1003

Other trials in Philippines

Thailand4 sites

  • King Chulalongkorn Memorial Hospital

    Bangkok, 10330

  • Siriraj Hospital

    Bangkok, 10700

  • Songklanagarind Hospital

    Hat Yai, Changwat Songkhla, 90110

  • Thammasat University Hospital

    Pathum Thani, 12120

Other trials in Thailand

Canada2 sites

  • Toronto General Hospital

    Toronto, Ontario, M5G 2L4

  • Vancouver General Hospital

    Vancouver, British Columbia

Other trials in Canada

Hong Kong1 site

  • Queen Mary Hospital

    Hong Kong

Other trials in Hong Kong

Malaysia1 site

  • University Malaya Medical Centre

    Kuala Lumpur, 59100

Other trials in Malaysia

About this study

Official title: A Phase III, Randomized, Double-Blinded, Dummy-Controlled Study of the Efficacy and Safety of ThermoDox® (Thermally Sensitive Liposomal Doxorubicin) in Combination With Radiofrequency Ablation (RFA) Compared to RFA-Alone in the Treatment of Non-Resectable Hepatocellular Carcinoma

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).

Read the detailed description

This will be a Phase III, randomized, double-blinded, dummy-controlled, efficacy, and safety study of ThermoDox plus RFA versus RFA plus dummy infusion.

The 50 mg/m2 ThermoDox or dummy infusion will be administered IV over 30 minutes. As part of blinded pre-medication ThermoDox treated subjects will receive 20 mg of dexamethasone orally 48 hours prior to the drug infusion for infusion reaction prophylaxis. Subjects on the control arm will receive a matching dummy pre-medication pill orally at 48 hours prior to infusion of the study treatment. Thirty minutes prior to receiving the ThermoDox infusion, subjects will receive a blinded dose of 20 mg of IV dexamethasone, 50 mg IV diphenhydramine and either 50 mg of IV ranitidine or 20 mg of IV famotidine. Subjects on the control arm will receive a masked dummy pre-medication pill orally at 48 hours prior to infusion of the study medication, and a dummy infusion 30 minutes prior to dummy infusion of D5W (250 cc of 5% Dextrose solution). RFA will be initiated approximately at a minimum of 15 minutes after the initiation of study drug infusion and should be completed no later than 3 hours after study drug infusion initiation. The total length of the RFA procedure is proportional to the size of the tumor(s) involved and is anticipated to range from 12 to 60 minutes for each lesion with an estimated overall procedure time of less than 3 hours.

Subjects with incomplete ablations will be re-treated to complete the ablation according to the treatment assigned at randomization. The completion of an ablation in this manner will restart the timeline of the study-related visits/procedures. This repeated ablation procedure cannot occur earlier than 21 days post-ablation but no later than 14 days after the first post-ablation CT scan assessment. These subjects will start over at screening (see Table 1). If a complete ablation is not achieved after these two study treatments, the subject will be considered a treatment failure and the patient will be discontinued and followed for survival only.

Subjects who recur with local and/or distant intrahepatic HCC after a complete initial ablation will have met the primary endpoint of progression-free survival. However, if these subjects have lesions that are amenable to RFA the standard of care is to consider them for repeat RFA. Therefore, these subjects may receive treatment to which they were randomized if they continue to meet the inclusion and exclusion criteria of the protocol. Subjects who develop any extrahepatic lesion will have met the primary endpoint and will be discontinued from study treatment but will still be followed for overall survival.

Dynamic Contrast CT imaging will be used to assess the effectiveness of the ablation therapy. The blind will be maintained at the level of CT scan reads. All protocol-specified CT images will be centrally read and assessed by the endpoint committee in a blinded fashion. Posttreatment CT scans will be obtained at months 1, 3, 5, 7, 9 and 12 and every three months thereafter until withdrawal. Adverse event assessments and laboratory examinations will occur at each visit. All subjects will be monitored throughout the investigational period.

Patients that meet inclusion/exclusion criteria may be at risk for contrast-induced nephropathy (CIN) when undergoing the required CT with contrast procedures. The investigators must be mindful of the risk factors (e.g. diabetes, borderline renal function) associated with CIN and employ strategies to reduce the risk of CIN. In subjects with diabetes or borderline renal function (creatinine greater than 1.5 mg/dL) special precautions (e.g. hydration, contrast dose reduction, follow up creatinine determination) should be employed. An accepted procedure is adequate intravenous volume expansion with isotonic saline (1.0 - 1.5 mL/kg per hour) for 3-12 hours before the procedure and continued for 6-24 hours.

All randomized subjects will be followed for safety and overall survival.

Being tested
ThermoDox, 5% Dextrose Solution
Keywords
hepatocellular carcinoma, liver cancer
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ThermoDoxDrug

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

  • 5% Dextrose SolutionDrug

    Single 30 minute intravenous infusion

Study groups in NCT00617981
Study groupRoleWhat they receive
ThermoDox + RFAExperimentalThermoDox 50 mg/m2 start infusion over 30 minutes about 15 minutes before radiofrequency ablation begins.
Receives: Drug: ThermoDox
Sham + RFASham comparatorSham infusion over 30 minutes about 15 minutes before radiofrequency ablation begins.
Receives: Drug: 5% Dextrose Solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 3 years

Secondary outcomes (4)

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

    Measured: 3 years

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

    Number of participants with significant symptom deterioration, defined as greater than or equal to 4-point increase from baseline in the eight-item Functional Assessment of Cancer Therapy-Hepatobiliary Symptom Index.

    Measured: 3 years

  3. Number of Participants With Local Recurrence

    Number of participants with local progression in the intent-to-treat (ITT) population.

    Measured: 3 years

  4. Evaluation of Safety

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2008 (estimated)
  2. Study startMay 2008
  3. Primary completionJan 2013
  4. Study completionAug 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
701 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00617981
Sponsor's protocol ID
104-06-301
Status last verified
May 2024
First submitted
6 Feb 2008
Last updated
3 May 2024
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ThermoDox and 5% Dextrose Solution in people with Hepatocellular Carcinoma, run by Imunon at 79 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 79 sites in China, Japan, South Korea, United States, Taiwan and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00617981.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2024.

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