Combination Chemotherapy and Thalidomide in Treating Younger Patients Undergoing Surgery For Newly Diagnosed Liver Cancer

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Liver Cancer

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

cisplatin

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

thalidomide

Intervention Type DRUG

adjuvant therapy

Intervention Type PROCEDURE

conventional surgery

Intervention Type PROCEDURE

neoadjuvant therapy

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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

Maximum Eligible Age

29 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Bruce Morland, MD

Role: STUDY_CHAIR

Birmingham Children's Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Our Lady's Hospital for Sick Children Crumlin

Dublin, , Ireland

Site Status

Birmingham Children's Hospital

Birmingham, England, United Kingdom

Site Status

Institute of Child Health at University of Bristol

Bristol, England, United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Site Status

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, England, United Kingdom

Site Status

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, United Kingdom

Site Status

Royal London Hospital

London, England, United Kingdom

Site Status

Great Ormond Street Hospital for Children

London, England, United Kingdom

Site Status

Royal Manchester Children's Hospital

Manchester, England, United Kingdom

Site Status

Sir James Spence Institute of Child Health at Royal Victoria Infirmary

Newcastle upon Tyne, England, United Kingdom

Site Status

Queen's Medical Centre

Nottingham, England, United Kingdom

Site Status

Oxford Radcliffe Hospital

Oxford, England, United Kingdom

Site Status

Children's Hospital - Sheffield

Sheffield, England, United Kingdom

Site Status

Southampton General Hospital

Southampton, England, United Kingdom

Site Status

Royal Marsden - Surrey

Sutton, England, United Kingdom

Site Status

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, United Kingdom

Site Status

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, United Kingdom

Site Status

Royal Hospital for Sick Children

Edinburgh, Scotland, United Kingdom

Site Status

Royal Hospital for Sick Children

Glasgow, Scotland, United Kingdom

Site Status

Childrens Hospital for Wales

Cardiff, Wales, United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Ireland United Kingdom