Combination Chemotherapy With or Without Amifostine in Treating Young Patients With Liver Cancer

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ClinicalTrials.gov Identifier: NCT00003994

Recruitment Status : Completed

First Posted : January 27, 2003

Last Update Posted : June 14, 2013

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Children's Oncology Group

Study Description

Brief 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. 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.

Condition or disease	Intervention/treatment	Phase
Childhood Hepatoblastoma Recurrent Childhood Liver Cancer Stage I Childhood Liver Cancer	Procedure: therapeutic conventional surgery Drug: cisplatin Drug: vincristine sulfate Drug: fluorouracil Drug: amifostine trihydrate Drug: carboplatin	Phase 3

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Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	277 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Intergroup Protocol for Treatment of Children With Hepatoblastoma
Study Start Date :	March 1999
Actual Primary Completion Date :	October 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Drug Information available for: Amifostine Amifostine monohydrate

Genetic and Rare Diseases Information Center resources: Hepatoblastoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm I (cisplatin, vincristine sulfate, fluorouracil) 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.	Procedure: therapeutic conventional surgery Undergo surgical resection Drug: cisplatin Given IV Other Names: CACP CDDP CPDD DDP Drug: vincristine sulfate Given IV Other Names: leurocristine sulfate VCR Vincasar PFS Drug: fluorouracil Given IV Other Names: 5-fluorouracil 5-Fluracil 5-FU
Experimental: Arm II (cisplatin, vincristine, fluorouracil, amifostine) 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.	Procedure: therapeutic conventional surgery Undergo surgical resection Drug: cisplatin Given IV Other Names: CACP CDDP CPDD DDP Drug: vincristine sulfate Given IV Other Names: leurocristine sulfate VCR Vincasar PFS Drug: fluorouracil Given IV Other Names: 5-fluorouracil 5-Fluracil 5-FU Drug: amifostine trihydrate Given IV Other Names: ethiofos Ethyol gammaphos WR-2721
Experimental: Arm III (carboplatin, cisplatin) 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.	Procedure: therapeutic conventional surgery Undergo surgical resection Drug: cisplatin Given IV Other Names: CACP CDDP CPDD DDP Drug: carboplatin Given IV Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin
Experimental: Arm IV (carboplain, cisplatin, amifostine) 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.	Procedure: therapeutic conventional surgery Undergo surgical resection Drug: cisplatin Given IV Other Names: CACP CDDP CPDD DDP Drug: amifostine trihydrate Given IV Other Names: ethiofos Ethyol gammaphos WR-2721 Drug: carboplatin Given IV Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin

Outcome Measures

Primary Outcome Measures :

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.

Eligibility Criteria

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Ages Eligible for Study:	up to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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:
- 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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00003994

Locations

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United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

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Principal Investigator:	Howard Katzenstein	Children's Oncology Group

More Information

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Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00003994
Other Study ID Numbers:	P9645 NCI-2012-02306 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) COG-P9645 ( Other Identifier: Children's Oncology Group ) CCG-P9645 ( Other Identifier: Children's Cancer Group ) POG-9645 ( Other Identifier: Pediatric Oncology Group ) CDR0000067200 ( Other Identifier: Clinical Trials.gov ) U10CA098543 ( U.S. NIH Grant/Contract )
First Posted:	January 27, 2003 Key Record Dates
Last Update Posted:	June 14, 2013
Last Verified:	June 2013

Additional relevant MeSH terms:

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Liver Neoplasms Hepatoblastoma Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Liver Diseases Neoplasms, Complex and Mixed Neoplasms by Histologic Type Carboplatin Fluorouracil Vincristine Amifostine	Antineoplastic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Radiation-Protective Agents Protective Agents

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