Clinical trial NCT00003994: Combination Chemotherapy With or Without Amifostine in Treating Young Patients With Liver Cancer
Official title: Intergroup Protocol for Treatment of Children With Hepatoblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Childhood Hepatoblastoma
Recurrent Childhood Liver Cancer
Stage I Childhood Liver Cancer
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 277
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Event-free survival (EFS) rates
timeFrame: Up to 8 years
measure: Toxicity rates assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC)
timeFrame: Up to 8 years
Secondary outcomes:
Other outcomes:
Locations:
city: Arcadia
country: United States
facility: Children's Oncology Group
state: California
Study officials:
affiliation: Children's Oncology Group
name: Howard Katzenstein
role: PRINCIPAL_INVESTIGATOR
References: