Liver CancerPhase 2NCT00276705
Combination Chemotherapy and Thalidomide in Treating Younger Patients Undergoing Surgery For Newly Diagnosed Liver Cancer
A Phase 2 study testing cisplatin, cyclophosphamide and doxorubicin hydrochloride in people with Liver Cancer, run by Children's Cancer and Leukaemia Group at 21 sites in 2 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as cisplatin and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Read more about this study
- Who is it for?
- Ages Up to 29 years
- Conditions the study is for
- Liver Cancer
- What is being tested?
- cisplatin, cyclophosphamide and doxorubicin hydrochloride
- Type of treatment
- Surgery or procedure
- How many people
- 47 participants
- Where
- 21 sitesin 2 countries
- Study dates
- Jun 2005to Apr 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 Up to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Histologically confirmed hepatocellular carcinoma (HCC) family of tumors by percutaneous needle biopsy (unless primary tumor resection is attempted)
- Newly diagnosed disease
- No recurrent disease
- Fibrolamellar and transitional variants
- Noncirrhotic disease
- If suspicious of liver cirrhosis (e.g., abnormal liver function tests and/or positive viral serology and/or radiological evidence) at diagnosis, patient must undergo biopsy of normal liver to exclude liver cirrhosis
PATIENT CHARACTERISTICS:
- Able to follow the protocol
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Life expectancy at least 3 months
- Glomerular filtration rate ≥ 75-50% of the lower limit of normal for age (≥ 60 mL/min for patients ≥ 2 years old)
- Cardiac ejection fraction ≥ 29% at baseline ECHO
PRIOR CONCURRENT THERAPY:
- No prior treatment for HCC
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United Kingdom20 sites
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, AB25 2ZG
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, BT12 6BE
Birmingham Children's Hospital
Birmingham, England, B4 6NH
Institute of Child Health at University of Bristol
Bristol, England, BS2 8AE
Addenbrooke's Hospital
Cambridge, England, CB2 2QQ
Childrens Hospital for Wales
Cardiff, Wales, CF14 4XW
Royal Hospital for Sick Children
Edinburgh, Scotland, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, G3 8SJ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
Leicester Royal Infirmary
Leicester, England, LE1 5WW
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, L12 2AP
Royal London Hospital
London, England, E1 1BB
Great Ormond Street Hospital for Children
London, England, WC1N 3JH
Royal Manchester Children's Hospital
Manchester, England, M27 4HA
Sir James Spence Institute of Child Health at Royal Victoria Infirmary
Newcastle upon Tyne, England, NE1 4LP
Queen's Medical Centre
Nottingham, England, NG7 2UH
Oxford Radcliffe Hospital
Oxford, England, 0X3 9DU
Children's Hospital - Sheffield
Sheffield, England, S10 2TH
Southampton General Hospital
Southampton, England, SO16 6YD
Royal Marsden - Surrey
Sutton, England, SM2 5PT
About this study
Official title: Hepatocellular Carcinoma Family of Tumours In Children / Adolescents and Young Adults
RATIONALE: Drugs used in chemotherapy, such as cisplatin and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Thalidomide may stop the growth of liver cancer by blocking blood flow to the tumor. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Giving combination chemotherapy, thalidomide, and chemoembolization before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving thalidomide together with chemotherapy after surgery may kill any remaining tumor cells and prevent the tumor from coming back.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy and thalidomide together with chemoembolization works in treating younger patients undergoing surgery for newly diagnosed liver cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine the event-free and overall survival of younger patients undergoing surgery for newly diagnosed, noncirrhotic hepatocellular carcinoma (HCC) treated with neoadjuvant cisplatin, doxorubicin hydrochloride, and thalidomide (PLADOTH) followed by transarterial hepatic arterial chemoembolization comprising cisplatin and doxorubicin hydrochloride and adjuvant cyclophosphamide and thalidomide.
- Determine the efficacy and tolerability of PLADOTH in patients with initially unresectable noncirrhotic HCC treated with this regimen.
- Determine the rate of complete surgical resection by encouragement of liver transplantation in the treatment strategy as a valid option for tumor removal when partial liver resection or other surgical options remain unfeasible for patients treated with this regimen.
- Determine the long-term remission and decreased relapse rates of patients treated with this regimen based on the postoperative regimen.
Secondary
- Determine the response rate of patients treated with this regimen after treatment with PLADOTH.
- Determine the short-term toxicity and feasibility of PLADOTH in patients treated with this regimen.
- Determine the efficacy and toxicity of the postoperative regimen in terms of maintenance and duration of complete remission (no more evidence of disease and normal alpha-fetoprotein, if initially elevated) in patients treated with this regimen.
- Determine whether response to PLADOTH by the RECIST criteria can be used for better monitoring of response of patients treated with this regimen.
- Determine whether the rate of fall of serum VEGF and bFGF levels during PLADOTH can be used as prognostic factors for short-term and long-term outcome in patients treated with this regimen.
- Determine the feasibility of chemoembolization in patients treated with this regimen who do not respond to PLADOTH.
- Determine which subset of tumors may benefit from an angiostatic treatment approach based on radiological, surgical, and pathological data collected from patients treated with this regimen.
- Identify possible novel factors that might influence treatment choice and disease outcome based on radiological, surgical, and pathological data collected from patients treated with this regimen.
- Determine guidelines for diagnostic, therapeutic, and follow-up management that would improve clinical care for patients treated with this regimen.
OUTLINE: This is a multicenter, nonrandomized, open-label study.
All patients undergo either tumor biopsy or resection. Patients with localized resectable tumors undergo resection. They then proceed directly to the postoperative treatment. Patients with initially unresectable tumors undergo biopsy then proceed to the pre-operative regimen.
- Pre-operative chemotherapy and thalidomide (PLADOTH): Patients receive PLADOTH comprising cisplatin IV continuously over 24 hours on day 1, doxorubicin hydrochloride IV over 1 hour on days 1 and 2 (or IV continuously over 24 hours on days 1 and 3), and oral thalidomide daily on days 1-21. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients whose tumors are deemed resectable proceed to surgery. Patients with responding disease but whose tumors remain unresectable proceed to chemoembolization or receive 2 additional courses of PLADOTH.
- Transarterial hepatic artery chemoembolization (TACE): Patients undergo TACE comprising cisplatin and doxorubicin hydrochloride administered through a catheter placed near the tumor. TACE may be repeated every 3-4 weeks for as long as disease continues to respond or until the tumor becomes resectable. Patients also receive oral thalidomide once daily during TACE. Once the tumor is deemed resectable, patients proceed to surgery.
- Surgery: Patients undergo surgical resection of the tumor. Patients undergo either partial or total hepatectomy followed by a liver transplant and lung surgery, if necessary. Patients then proceed to the postoperative treatment.
- Postoperative treatment: Beginning within 6 weeks after surgery, patients receive oral cyclophosphamide once every other day and oral thalidomide once daily for up to 1 year in the absence of disease progression or unacceptable toxicity.
Patients with metastatic disease who show disease progression at any time during treatment go off study and receive individual advice regarding further treatment based on the decision of the principal investigator.
After completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.
- Conditions
- Liver Cancer
- Being tested
- cisplatin, cyclophosphamide, doxorubicin hydrochloride, thalidomide, adjuvant therapy
- Keywords
- adult primary hepatocellular carcinoma, childhood hepatocellular carcinoma, advanced adult primary liver cancer, localized resectable adult primary liver cancer, localized unresectable adult primary liver cancer, stage I childhood liver cancer, stage II childhood liver cancer, stage III childhood liver cancer, stage IV childhood liver cancer
- Medical subject headings
- Liver Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cisplatinDrug
cyclophosphamideDrug
thalidomideDrug
adjuvant therapyProcedure or surgery
conventional surgeryProcedure or surgery
neoadjuvant therapyProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free and overall survival following tumor resection
Secondary outcomes (1)
Efficacy and tolerability following course 2 and 4 of pre-operative chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2006 (estimated)
- Study startJun 2005
- Primary completionApr 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 47 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Cancer and Leukaemia Group
- Sponsor type
- University, hospital or other
- Investigators
- Bruce Morland, MD, Study chair, Birmingham Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00276705
- Sponsor's protocol ID
- CDR0000454579
- Other IDs
- CCLG-LT-2005-05, CCLG-SIOPEL-HCC, CCLG-SIOPEL-5, EU-20590, EUDRACT-2005-000427-42
- Status last verified
- Jun 2009
- First submitted
- 12 Jan 2006
- Last updated
- 17 Sep 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatocellular Carcinoma Family of Tumours In Children / Adolescents and Young Adults
- ClinicalTrials.gov ID
- NCT00276705
- Acronym / sponsor ID
- CDR0000454579
- Conditions
- Liver Cancer
- Keywords
- adult primary hepatocellular carcinoma, childhood hepatocellular carcinoma, advanced adult primary liver cancer, localized resectable adult primary liver cancer, localized unresectable adult primary liver cancer, stage I childhood liver cancer, stage II childhood liver cancer, stage III childhood liver cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 47 participants (estimated)
- Lead sponsor
- Children's Cancer and Leukaemia GroupUniversity, hospital or other
- Study start
- Jun 2005
- Primary completion
- Apr 2009 (estimated)
- First posted
- 13 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as cisplatin and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Thalidomide may stop the growth of liver cancer by blocking blood flow to the tumor. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Giving combination chemotherapy, thalidomide, and chemoembolization before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving thalidomide together with chemotherapy after surgery may kill any remaining tumor cells and prevent the tumor from coming back.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy and thalidomide together with chemoembolization works in treating younger patients undergoing surgery for newly diagnosed liver cancer.
Detailed description
OBJECTIVES:
Primary
- Determine the event-free and overall survival of younger patients undergoing surgery for newly diagnosed, noncirrhotic hepatocellular carcinoma (HCC) treated with neoadjuvant cisplatin, doxorubicin hydrochloride, and thalidomide (PLADOTH) followed by transarterial hepatic arterial chemoembolization comprising cisplatin and doxorubicin hydrochloride and adjuvant cyclophosphamide and thalidomide.
- Determine the efficacy and tolerability of PLADOTH in patients with initially unresectable noncirrhotic HCC treated with this regimen.
- Determine the rate of complete surgical resection by encouragement of liver transplantation in the treatment strategy as a valid option for tumor removal when partial liver resection or other surgical options remain unfeasible for patients treated with this regimen.
- Determine the long-term remission and decreased relapse rates of patients treated with this regimen based on the postoperative regimen.
Secondary
- Determine the response rate of patients treated with this regimen after treatment with PLADOTH.
- Determine the short-term toxicity and feasibility of PLADOTH in patients treated with this regimen.
- Determine the efficacy and toxicity of the postoperative regimen in terms of maintenance and duration of complete remission (no more evidence of disease and normal alpha-fetoprotein, if initially elevated) in patients treated with this regimen.
- Determine whether response to PLADOTH by the RECIST criteria can be used for better monitoring of response of patients treated with this regimen.
- Determine whether the rate of fall of serum VEGF and bFGF levels during PLADOTH can be used as prognostic factors for short-term and long-term outcome in patients treated with this regimen.
- Determine the feasibility of chemoembolization in patients treated with this regimen who do not respond to PLADOTH.
- Determine which subset of tumors may benefit from an angiostatic treatment approach based on radiological, surgical, and pathological data collected from patients treated with this regimen.
- Identify possible novel factors that might influence treatment choice and disease outcome based on radiological, surgical, and pathological data collected from patients treated with this regimen.
- Determine guidelines for diagnostic, therapeutic, and follow-up management that would improve clinical care for patients treated with this regimen.
OUTLINE: This is a multicenter, nonrandomized, open-label study.
All patients undergo either tumor biopsy or resection. Patients with localized resectable tumors undergo resection. They then proceed directly to the postoperative treatment. Patients with initially unresectable tumors undergo biopsy then proceed to the pre-operative regimen.
- Pre-operative chemotherapy and thalidomide (PLADOTH): Patients receive PLADOTH comprising cisplatin IV continuously over 24 hours on day 1, doxorubicin hydrochloride IV over 1 hour on days 1 and 2 (or IV continuously over 24 hours on days 1 and 3), and oral thalidomide daily on days 1-21. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients whose tumors are deemed resectable proceed to surgery. Patients with responding disease but whose tumors remain unresectable proceed to chemoembolization or receive 2 additional courses of PLADOTH.
- Transarterial hepatic artery chemoembolization (TACE): Patients undergo TACE comprising cisplatin and doxorubicin hydrochloride administered through a catheter placed near the tumor. TACE may be repeated every 3-4 weeks for as long as disease continues to respond or until the tumor becomes resectable. Patients also receive oral thalidomide once daily during TACE. Once the tumor is deemed resectable, patients proceed to surgery.
- Surgery: Patients undergo surgical resection of the tumor. Patients undergo either partial or total hepatectomy followed by a liver transplant and lung surgery, if necessary. Patients then proceed to the postoperative treatment.
- Postoperative treatment: Beginning within 6 weeks after surgery, patients receive oral cyclophosphamide once every other day and oral thalidomide once daily for up to 1 year in the absence of disease progression or unacceptable toxicity.
Patients with metastatic disease who show disease progression at any time during treatment go off study and receive individual advice regarding further treatment based on the decision of the principal investigator.
After completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cisplatin | Drug | – |
| cyclophosphamide | Drug | – |
| doxorubicin hydrochloride | Drug | – |
| thalidomide | Drug | – |
| adjuvant therapy | Procedure or surgery | – |
| conventional surgery | Procedure or surgery | – |
| neoadjuvant therapy | Procedure or surgery | – |
Primary outcome
Event-free and overall survival following tumor resection
1 secondary outcome
Efficacy and tolerability following course 2 and 4 of pre-operative chemotherapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce Morland, MD study chair
Birmingham Children's Hospital
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cisplatin, cyclophosphamide and doxorubicin hydrochloride in people with Liver Cancer, run by Children's Cancer and Leukaemia Group at 21 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 17 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United Kingdom, Ireland. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Event-free and overall survival following tumor resection. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Sep 2013.