Liver CancerPhase 2NCT00471484
Combination Chemotherapy and Interferon Alfa-2b in Treating Patients With Nonmetastatic Liver Cancer That Cannot Be Removed by Surgery
A Phase 2 study testing recombinant interferon alfa-2b, doxorubicin hydrochloride and fluorouracil in people with Liver Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, doxorubicin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Interferon alfa may interfere with the growth of tumor cells. Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- Liver Cancer
- What is being tested?
- recombinant interferon alfa-2b, doxorubicin hydrochloride and fluorouracil
- Type of treatment
- Surgery or procedure
- How many people
- 54 participants
- Where
- 1 siteSingapore
- Study dates
- Mar 2007to not given
- 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 16 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed hepatocellular carcinoma
- Advanced, unresectable, nonmetastatic disease
- Multifocal disease within the same lobe of the liver allowed
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
- No intractable ascites that cannot be controlled by medical therapy
- No extrahepatic metastases
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 3 months
- WBC ≥ 3,000/mm³
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9 g/dL
- Bilirubin ≤ 2.9 mg/dL
- AST and ALT ≤ 5 times upper reference range (URR)
- Albumin > 30 g/L
- Creatinine ≤ 1.5 times URR
- Creatinine clearance > 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after completion of study therapy
- No other prior malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
- No concurrent substantial medical illness, such as cardiac or renal disease
- MUGA heart study normal
- No history of allergic reactions attributed to compounds of similar chemical or biological composition used in the study
- No history of autoimmune disease
- No thyroid dysfunction
- No active hepatitis B or C flare or chronic active hepatitis
- Hepatitis B surface antigen (HBsAg) status known
- If HBsAg is negative, anti-HBc antibodies should be tested; if anti-HBc is positive, then hepatitis B virus (HBV) DNA detection should be performed to discern presence of mutant HBV carriage
- No alcohol or drug abuse
- No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- No psychiatric illness or social situation that would preclude study compliance
- Patients with a history of depression or psychiatric disorders are ineligible
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy and/or radiotherapy
- No other concurrent investigational agents
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National Cancer Centre - Singapore
Singapore, 169610
Donald Poon, MD, 65-6-436-8000
About this study
Official title: A Phase II Trial of Oxaliplatin/Adriamycin/5 Fluorouracil in Continuous Infusion / Interferon α-2b (OXAFI) Combination as Neoadjuvant Therapy in Unresectable Non-Metastatic Hepatocellular Carcinoma
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, doxorubicin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Interferon alfa may interfere with the growth of tumor cells. Giving combination chemotherapy together with interferon alfa may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with interferon alfa-2b works in treating patients with nonmetastatic liver cancer that cannot be removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- Determine the response rate in patients with unresectable, nonmetastatic hepatocellular carcinoma treated with neoadjuvant oxaliplatin, doxorubicin hydrochloride, fluorouracil, and recombinant interferon alfa-2b.
Secondary
- Determine the overall survival of patients treated with this regimen.
- Determine the progression-free survival of patients treated with this regimen.
- Determine the rate of conversion to resectability of tumor in patients treated with this regimen.
- Determine the toxicity profile of this regimen in these patients.
- Assess the quality of life of patients treated with this regimen.
- Correlate changes in serological markers of angiogenesis before and after treatment with clinical outcome in these patients.
- Correlate and validate the use of functional imaging before and after treatment with clinical outcome in these patients.
OUTLINE: Patients receive neoadjuvant OXAFI therapy comprising oxaliplatin IV and doxorubicin hydrochloride IV on days 1, 8 and 15; fluorouracil IV continuously on days 1-28; and recombinant interferon alfa-2b subcutaneously three times weekly in weeks 1-4. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients receive at least 2 courses of neoadjuvant therapy before undergoing evaluation for response. Patients whose disease becomes resectable after achieving a complete or partial response proceed to surgery. Patients whose disease remains unresectable are reevaluated until their disease either becomes resectable, they complete neoadjuvant therapy, or they meet discontinuation criteria.
At least 2 weeks after receiving neoadjuvant therapy, patients whose disease is resectable undergo surgery for potentially complete resection of their tumors with curative intent. Patients who achieve complete resection proceed to adjuvant therapy.
At least 4 weeks after surgery, patients may restart OXAFI as adjuvant therapy, provided they have fully recovered from surgery and have received fewer than 6 courses of neoadjuvant therapy. Adjuvant therapy repeats every 28 days for a total of 6 courses (including neoadjuvant OXAFI) in the absence of disease progression or unacceptable toxicity.
Patients undergo blood and tissue collection at baseline and periodically during study for evaluation of circulating and tissue biomarkers of angiogenesis. Serum from venous blood samples is analyzed for concentration of VEGF by ELISA. Tumor tissue obtained before and after treatment is examined for tumor VEGF expression, microvessel density, and cellular proliferation by IHC.
Patients complete quality of life questionnaires at baseline, monthly during study treatment, after course 6 of neoadjuvant chemotherapy, or upon discontinuation of study treatment.
Patients are followed periodically for up to 5 years after curative resection of their tumors.
PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.
- Conditions
- Liver Cancer
- Being tested
- recombinant interferon alfa-2b, doxorubicin hydrochloride, fluorouracil, oxaliplatin, diagnostic laboratory biomarker analysis
- Keywords
- adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, advanced adult primary liver cancer, childhood hepatocellular carcinoma, 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.
recombinant interferon alfa-2bBiological
fluorouracilDrug
oxaliplatinDrug
diagnostic laboratory biomarker analysisOther
immunoenzyme techniqueOther
adjuvant therapyProcedure or surgery
biopsyProcedure or surgery
neoadjuvant therapyProcedure or surgery
therapeutic conventional surgeryProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective tumor response rate as measured by RECIST criteria
Secondary outcomes (2)
Serum VEGF levels
Tissue VEGF expression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2007 (estimated)
- Study startMar 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Investigators
- Donald Poon, MD, Study chair, National Cancer Centre, SingaporeKian Fong Foo, MD, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00471484
- Sponsor's protocol ID
- CDR0000543536
- Other IDs
- SINGAPORE-OC-GI-01-06, SINGAPORE-IRB-06-16-HEP, SINGAPORE-CTC0600327, SPRI-SINGAPORE-OC-GI-01-06
- Status last verified
- Nov 2008
- First submitted
- 8 May 2007
- Last updated
- 22 Jun 2011
- Results posted
- No
Publications
Ang MK, Poon D, Foo KF, Chung YF, Chow P, Wan WK, Thng CH, Ooi L. A new chemoimmunotherapy regimen (OXAFI) for advanced hepatocellular carcinoma. Hematol Oncol Stem Cell Ther. 2008 Jul-Sep;1(3):159-65. doi: 10.1016/s1658-3876(08)50024-0.
PubMed 20063546
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Oxaliplatin/Adriamycin/5 Fluorouracil in Continuous Infusion / Interferon α-2b (OXAFI) Combination as Neoadjuvant Therapy in Unresectable Non-Metastatic Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT00471484
- Acronym / sponsor ID
- CDR0000543536
- Conditions
- Liver Cancer
- Keywords
- adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, advanced adult primary liver cancer, childhood hepatocellular carcinoma, stage III childhood liver cancer, stage IV childhood liver cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- Mar 2007
- First posted
- 10 May 2007 (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 oxaliplatin, doxorubicin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Interferon alfa may interfere with the growth of tumor cells. Giving combination chemotherapy together with interferon alfa may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with interferon alfa-2b works in treating patients with nonmetastatic liver cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES:
Primary
- Determine the response rate in patients with unresectable, nonmetastatic hepatocellular carcinoma treated with neoadjuvant oxaliplatin, doxorubicin hydrochloride, fluorouracil, and recombinant interferon alfa-2b.
Secondary
- Determine the overall survival of patients treated with this regimen.
- Determine the progression-free survival of patients treated with this regimen.
- Determine the rate of conversion to resectability of tumor in patients treated with this regimen.
- Determine the toxicity profile of this regimen in these patients.
- Assess the quality of life of patients treated with this regimen.
- Correlate changes in serological markers of angiogenesis before and after treatment with clinical outcome in these patients.
- Correlate and validate the use of functional imaging before and after treatment with clinical outcome in these patients.
OUTLINE: Patients receive neoadjuvant OXAFI therapy comprising oxaliplatin IV and doxorubicin hydrochloride IV on days 1, 8 and 15; fluorouracil IV continuously on days 1-28; and recombinant interferon alfa-2b subcutaneously three times weekly in weeks 1-4. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients receive at least 2 courses of neoadjuvant therapy before undergoing evaluation for response. Patients whose disease becomes resectable after achieving a complete or partial response proceed to surgery. Patients whose disease remains unresectable are reevaluated until their disease either becomes resectable, they complete neoadjuvant therapy, or they meet discontinuation criteria.
At least 2 weeks after receiving neoadjuvant therapy, patients whose disease is resectable undergo surgery for potentially complete resection of their tumors with curative intent. Patients who achieve complete resection proceed to adjuvant therapy.
At least 4 weeks after surgery, patients may restart OXAFI as adjuvant therapy, provided they have fully recovered from surgery and have received fewer than 6 courses of neoadjuvant therapy. Adjuvant therapy repeats every 28 days for a total of 6 courses (including neoadjuvant OXAFI) in the absence of disease progression or unacceptable toxicity.
Patients undergo blood and tissue collection at baseline and periodically during study for evaluation of circulating and tissue biomarkers of angiogenesis. Serum from venous blood samples is analyzed for concentration of VEGF by ELISA. Tumor tissue obtained before and after treatment is examined for tumor VEGF expression, microvessel density, and cellular proliferation by IHC.
Patients complete quality of life questionnaires at baseline, monthly during study treatment, after course 6 of neoadjuvant chemotherapy, or upon discontinuation of study treatment.
Patients are followed periodically for up to 5 years after curative resection of their tumors.
PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older 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 |
|---|---|---|
| recombinant interferon alfa-2b | Biological | – |
| doxorubicin hydrochloride | Drug | – |
| fluorouracil | Drug | – |
| oxaliplatin | Drug | – |
| diagnostic laboratory biomarker analysis | Other | – |
| immunoenzyme technique | Other | – |
| immunohistochemistry staining method | Other | – |
| adjuvant therapy | Procedure or surgery | – |
| biopsy | Procedure or surgery | – |
| neoadjuvant therapy | Procedure or surgery | – |
| therapeutic conventional surgery | Procedure or surgery | – |
Primary outcome
Objective tumor response rate as measured by RECIST criteria
2 secondary outcomes
Serum VEGF levels
Tissue VEGF expression
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2011.
- Results publication: PubMed 20063546Ang MK, Poon D, Foo KF, Chung YF, Chow P, Wan WK, Thng CH, Ooi L. A new chemoimmunotherapy regimen (OXAFI) for advanced hepatocellular carcinoma. Hematol Oncol Stem Cell Ther. 2008 Jul-Sep;1(3):159-65. doi: 10.1016/s1658-3876(08)50024-0.
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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.
Donald Poon, MD study chair
National Cancer Centre, Singapore
Kian Fong Foo, MD
National Cancer Centre, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing recombinant interferon alfa-2b, doxorubicin hydrochloride and fluorouracil in people with Liver Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
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 22 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective tumor response rate as measured by RECIST criteria. 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 NCT00471484, which also lists 1 linked publication.
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 22 Jun 2011.