Childhood HepatoblastomaPhase 3NCT00003994
Combination Chemotherapy With or Without Amifostine in Treating Young Patients With Liver Cancer
A Phase 3 study testing therapeutic conventional surgery, cisplatin and vincristine sulfate in people with Childhood Hepatoblastoma and Recurrent Childhood Liver Cancer, run by Children's Oncology Group at 1 site in United States.
Trial summary
Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Childhood Hepatoblastoma, Recurrent Childhood Liver Cancer, Stage I Childhood Liver Cancer
- What is being tested?
- therapeutic conventional surgery, cisplatin and vincristine sulfate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 277 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 1999to Oct 2007
- Phase
- Phase 3
- 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 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically proven hepatoblastoma
- Any stage allowed(stages II-IV closed to accrual as of 11-25-03)
- Stratum 1 (stage I):
- Pure fetal histology
- Complete surgical resection of tumor
- Stratum 2 (stages I or II) (stage II closed to accrual as of 11-25-03), meeting 1 of the following criteria:
Show all 23Show fewer
- Complete resection of tumor with histology other than pure fetal
- Gross resection of tumor, including resected tumors with preoperative/intraoperative rupture
- Stratum 3 (stages III or IV) (stages III and IV closed to accrual as of 11-25-03), meeting 1 of the following criteria:
- Unresectable tumors
- Partial resection of tumor with measurable residual disease OR lymph node involvement
- Measurable metastatic disease to lungs or other organs
- No hepatocellular carcinoma
- Creatinine normal for age
- Glomerular filtration rate normal for age
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No prior biologic therapy
- No prior chemotherapy
- No prior endocrine therapy
- No prior radiotherapy
- See Disease Characteristics
- No prior therapy except tumor resection
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Oncology Group
Arcadia, California, 91006-3776
About this study
Official title: Intergroup Protocol for Treatment of Children With Hepatoblastoma
Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy. It is not yet known which chemotherapy regimen is most effective for children and young adults with liver cancer. This randomized phase III trial is studying giving combination chemotherapy together with amifostine to see how well it works compared to combination chemotherapy alone in treating patients with liver cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the response and efficacy of amifostine (amifostine trihydrate) in reducing the toxicity associated with platinum agents.
II. To test whether there is any effect of amifostine on event-free survival by comparing outcome of those treated with amifostine to those treated without on this study and with historic controls.
SECONDARY OBJECTIVES:
- To estimate the event-free survival of patients with stage I pure fetal histology treated with surgery alone.
II. To estimate the efficacy of amifostine in reducing the toxicity associated with cisplatinum in children with resected tumors receiving treatment 01 by randomizing to receive or not receive amifostine.
III. To collect tumor tissue in all patients for cytogenetic and genetic analysis in order to prospectively analyze biologic features and prognosis of patients with detailed treatment history, and to provide a resource for future biologic studies in hepatoblastoma.
IV. To assess the prognostic significance with respect to event-free survival of hepatoblastoma pathologic variants in patients with stage I tumors treated with surgery and chemotherapy (cisplatin + 5FU + vincristine).
OUTLINE: This is a randomized study. Patients are stratified according to disease stage (stage I pure fetal histology vs stage I other histology or stage II [stage II closed to accrual as of 11-25-03] vs stage III or IV [stages III and IV closed to accrual as of 11-25-03]). Patients are randomized to one of four treatment arms. (Arms III and IV closed to accrual as of 4-5-02) (Arm II closed to accrual as of 11-25-03)
All patients undergo surgical resection or attempted resection of tumor. Patients with pure fetal histology achieving complete tumor resection receive no further treatment. All other patients receive postoperative chemotherapy.
Arm I: Patients receive cisplatin IV over 4 hours on day 1, vincristine IV on days 3, 10, and 17, and fluorouracil on day 3.
Arm II (closed to accrual as of 11-25-03): Patients receive treatment as in arm I with the addition of amifostine IV over 15 minutes prior to cisplatin on day 1.
Arm III (closed to accrual as of 4-5-02): Patients receive carboplatin IV over 1 hour on day 1 and cisplatin IV over 4 hours on day 15.
Arm IV (closed to accrual as of 4-5-02): Patients receive treatment as in arm III with the addition of amifostine IV over 15 minutes prior to carboplatin on day 1.
Treatment repeats every 3 weeks for 4 courses in arms I and II (arm II closed to accrual as of 11-25-03) and every 4 weeks for 4 courses in arms III and IV (arms III and IV closed to accrual as of 4-5-02) in the absence of disease progression or unacceptable toxicity. Patients with stage III or IV disease (stages III and IV closed to accrual as of 11-25-03) undergo second look surgery and receive 2 additional courses of chemotherapy if achieving complete response after surgery.
Patients are followed monthly for 6 months, every 2 months for 2 years, every 3 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 356 patients will be accrued for this study within 5.5 years.
- Conditions
- Childhood Hepatoblastoma, Recurrent Childhood Liver Cancer, Stage I Childhood Liver Cancer
- Being tested
- therapeutic conventional surgery, cisplatin, vincristine sulfate, fluorouracil, amifostine trihydrate
- Medical subject headings
- Hepatoblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic conventional surgeryProcedure or surgery
Undergo surgical resection
cisplatinDrug
Also called CACP, CDDP, CPDD, DDP
Given IV
Also called leurocristine sulfate, VCR, Vincasar PFS
Given IV
fluorouracilDrug
Also called 5-fluorouracil, 5-Fluracil, 5-FU
Given IV
amifostine trihydrateDrug
Also called ethiofos, Ethyol, gammaphos, WR-2721
Given IV
carboplatinDrug
Also called Carboplat, CBDCA, JM-8, Paraplat
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (cisplatin, vincristine sulfate, fluorouracil) | Experimental | Patients receive therapeutic conventional surgery (tumor resection). Patients receive cisplatin IV over 4 hours on day 1, vincristine sulfate IV on days 3, 10, and 17, and fluorouracil on day 3. Receives: Procedure: therapeutic conventional surgery; Drug: cisplatin; Drug: vincristine sulfate; Drug: fluorouracil |
| Arm II (cisplatin, vincristine, fluorouracil, amifostine) | Experimental | Patients receive therapeutic conventional surgery (tumor resection). Patients receive treatment as in arm I with the addition of amifostine trihydrate IV over 15 minutes prior to cisplatin on day 1. Receives: Procedure: therapeutic conventional surgery; Drug: cisplatin; Drug: vincristine sulfate; Drug: fluorouracil; Drug: amifostine trihydrate |
| Arm III (carboplatin, cisplatin) | Experimental | Patients receive therapeutic conventional surgery (tumor resection). Patients receive carboplatin IV over 1 hour on day 1 and cisplatin IV over 4 hours on day 15. Receives: Procedure: therapeutic conventional surgery; Drug: cisplatin; Drug: carboplatin |
| Arm IV (carboplain, cisplatin, amifostine) | Experimental | Patients receive therapeutic conventional surgery (tumor resection). Patients receive treatment as in arm III with the addition of amifostine trihydrate IV over 15 minutes prior to carboplatin on day 1. Receives: Procedure: therapeutic conventional surgery; Drug: cisplatin; Drug: amifostine trihydrate; Drug: carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS) rates
EFS rates will be estimated using the method of Kaplan and Meier. Survival curves will be compared using stratified logrank tests.
Measured: Up to 8 years
Toxicity rates assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC)
For comparing the toxicity rates in the +/- amifostine arms, stratified binomial test for proportions (Mantel-Haenszel) will be used assuming no qualitative interaction between the two chemotherapy regimens and amifostine trihydrate.
Measured: Up to 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startMar 1999
- Primary completionOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood HepatoblastomaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 277 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Howard Katzenstein, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003994
- Sponsor's protocol ID
- P9645
- Other IDs
- NCI-2012-02306, COG-P9645, CCG-P9645, POG-9645, CDR0000067200, U10CA098543
- Status last verified
- Jun 2013
- First submitted
- 1 Nov 1999
- Last updated
- 14 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intergroup Protocol for Treatment of Children With Hepatoblastoma
- ClinicalTrials.gov ID
- NCT00003994
- Acronym / sponsor ID
- P9645
- Conditions
- Childhood Hepatoblastoma, Recurrent Childhood Liver Cancer, Stage I Childhood Liver Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 277 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 1999
- Primary completion
- Oct 2007 (actual)
- First posted
- 27 Jan 2003 (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.
Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy. It is not yet known which chemotherapy regimen is most effective for children and young adults with liver cancer. This randomized phase III trial is studying giving combination chemotherapy together with amifostine to see how well it works compared to combination chemotherapy alone in treating patients with liver cancer.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the response and efficacy of amifostine (amifostine trihydrate) in reducing the toxicity associated with platinum agents.
II. To test whether there is any effect of amifostine on event-free survival by comparing outcome of those treated with amifostine to those treated without on this study and with historic controls.
SECONDARY OBJECTIVES:
- To estimate the event-free survival of patients with stage I pure fetal histology treated with surgery alone.
II. To estimate the efficacy of amifostine in reducing the toxicity associated with cisplatinum in children with resected tumors receiving treatment 01 by randomizing to receive or not receive amifostine.
III. To collect tumor tissue in all patients for cytogenetic and genetic analysis in order to prospectively analyze biologic features and prognosis of patients with detailed treatment history, and to provide a resource for future biologic studies in hepatoblastoma.
IV. To assess the prognostic significance with respect to event-free survival of hepatoblastoma pathologic variants in patients with stage I tumors treated with surgery and chemotherapy (cisplatin + 5FU + vincristine).
OUTLINE: This is a randomized study. Patients are stratified according to disease stage (stage I pure fetal histology vs stage I other histology or stage II [stage II closed to accrual as of 11-25-03] vs stage III or IV [stages III and IV closed to accrual as of 11-25-03]). Patients are randomized to one of four treatment arms. (Arms III and IV closed to accrual as of 4-5-02) (Arm II closed to accrual as of 11-25-03)
All patients undergo surgical resection or attempted resection of tumor. Patients with pure fetal histology achieving complete tumor resection receive no further treatment. All other patients receive postoperative chemotherapy.
Arm I: Patients receive cisplatin IV over 4 hours on day 1, vincristine IV on days 3, 10, and 17, and fluorouracil on day 3.
Arm II (closed to accrual as of 11-25-03): Patients receive treatment as in arm I with the addition of amifostine IV over 15 minutes prior to cisplatin on day 1.
Arm III (closed to accrual as of 4-5-02): Patients receive carboplatin IV over 1 hour on day 1 and cisplatin IV over 4 hours on day 15.
Arm IV (closed to accrual as of 4-5-02): Patients receive treatment as in arm III with the addition of amifostine IV over 15 minutes prior to carboplatin on day 1.
Treatment repeats every 3 weeks for 4 courses in arms I and II (arm II closed to accrual as of 11-25-03) and every 4 weeks for 4 courses in arms III and IV (arms III and IV closed to accrual as of 4-5-02) in the absence of disease progression or unacceptable toxicity. Patients with stage III or IV disease (stages III and IV closed to accrual as of 11-25-03) undergo second look surgery and receive 2 additional courses of chemotherapy if achieving complete response after surgery.
Patients are followed monthly for 6 months, every 2 months for 2 years, every 3 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 356 patients will be accrued for this study within 5.5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm I (cisplatin, vincristine sulfate, fluorouracil) | Experimental | Procedure: therapeutic conventional surgery, Drug: cisplatin, Drug: vincristine sulfate, Drug: fluorouracilPatients receive therapeutic conventional surgery (tumor resection). Patients receive cisplatin IV over 4 hours on day 1, vincristine sulfate IV on days 3, 10, and 17, and fluorouracil on day 3. |
| Arm II (cisplatin, vincristine, fluorouracil, amifostine) | Experimental | Procedure: therapeutic conventional surgery, Drug: cisplatin, Drug: vincristine sulfate, Drug: fluorouracil, Drug: amifostine trihydratePatients receive therapeutic conventional surgery (tumor resection). Patients receive treatment as in arm I with the addition of amifostine trihydrate IV over 15 minutes prior to cisplatin on day 1. |
| Arm III (carboplatin, cisplatin) | Experimental | Procedure: therapeutic conventional surgery, Drug: cisplatin, Drug: carboplatinPatients receive therapeutic conventional surgery (tumor resection). Patients receive carboplatin IV over 1 hour on day 1 and cisplatin IV over 4 hours on day 15. |
| Arm IV (carboplain, cisplatin, amifostine) | Experimental | Procedure: therapeutic conventional surgery, Drug: cisplatin, Drug: amifostine trihydrate, Drug: carboplatinPatients receive therapeutic conventional surgery (tumor resection). Patients receive treatment as in arm III with the addition of amifostine trihydrate IV over 15 minutes prior to carboplatin on day 1. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (23 listed)
- Histologically proven hepatoblastoma
- Stratum 1 (stage I):
- Stratum 2 (stages I or II) (stage II closed to accrual as of 11-25-03), meeting 1 of the following criteria:
- Stratum 3 (stages III or IV) (stages III and IV closed to accrual as of 11-25-03), meeting 1 of the following criteria:
- No hepatocellular carcinoma
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| therapeutic conventional surgeryUndergo surgical resection | Procedure or surgery | Arm I (cisplatin, vincristine sulfate, fluorouracil), Arm II (cisplatin, vincristine, fluorouracil, amifostine), Arm III (carboplatin, cisplatin), Arm IV (carboplain, cisplatin, amifostine) |
| cisplatinAlso: CACP, CDDP, CPDD, DDPGiven IV | Drug | Arm I (cisplatin, vincristine sulfate, fluorouracil), Arm II (cisplatin, vincristine, fluorouracil, amifostine), Arm III (carboplatin, cisplatin), Arm IV (carboplain, cisplatin, amifostine) |
| vincristine sulfateAlso: leurocristine sulfate, VCR, Vincasar PFSGiven IV | Drug | Arm I (cisplatin, vincristine sulfate, fluorouracil), Arm II (cisplatin, vincristine, fluorouracil, amifostine) |
| fluorouracilAlso: 5-fluorouracil, 5-Fluracil, 5-FUGiven IV | Drug | Arm I (cisplatin, vincristine sulfate, fluorouracil), Arm II (cisplatin, vincristine, fluorouracil, amifostine) |
| amifostine trihydrateAlso: ethiofos, Ethyol, gammaphos, WR-2721Given IV | Drug | Arm II (cisplatin, vincristine, fluorouracil, amifostine), Arm IV (carboplain, cisplatin, amifostine) |
| carboplatinAlso: Carboplat, CBDCA, JM-8, ParaplatGiven IV | Drug | Arm III (carboplatin, cisplatin), Arm IV (carboplain, cisplatin, amifostine) |
Primary outcome
Event-free survival (EFS) rates
Time frame: Up to 8 years
EFS rates will be estimated using the method of Kaplan and Meier. Survival curves will be compared using stratified logrank tests.
Toxicity rates assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC)
Time frame: Up to 8 years
For comparing the toxicity rates in the +/- amifostine arms, stratified binomial test for proportions (Mantel-Haenszel) will be used assuming no qualitative interaction between the two chemotherapy regimens and amifostine trihydrate.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 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.
Howard Katzenstein principal investigator
Children's Oncology Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing therapeutic conventional surgery, cisplatin and vincristine sulfate in people with Childhood Hepatoblastoma and Recurrent Childhood Liver Cancer, run by Children's Oncology Group at 1 site in United States.
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 23 inclusion and 0 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 14 Jun 2013. 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 United States. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 survival (EFS) rates (time frame: Up to 8 years). The study lists 2 primary outcomes in all. 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 14 Jun 2013.