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NCT00003994 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2013-06-14

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
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
healthy Volunteers
false
maximum Age
21 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Procedure: therapeutic conventional surgery
    2. Drug: cisplatin
    3. Drug: vincristine sulfate
    4. Drug: fluorouracil
    label
    Arm I (cisplatin, vincristine sulfate, fluorouracil)
    type
    EXPERIMENTAL
  2. description
    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.
    intervention Names
    1. Procedure: therapeutic conventional surgery
    2. Drug: cisplatin
    3. Drug: vincristine sulfate
    4. Drug: fluorouracil
    5. Drug: amifostine trihydrate
    label
    Arm II (cisplatin, vincristine, fluorouracil, amifostine)
    type
    EXPERIMENTAL
  3. description
    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.
    intervention Names
    1. Procedure: therapeutic conventional surgery
    2. Drug: cisplatin
    3. Drug: carboplatin
    label
    Arm III (carboplatin, cisplatin)
    type
    EXPERIMENTAL
  4. description
    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.
    intervention Names
    1. Procedure: therapeutic conventional surgery
    2. Drug: cisplatin
    3. Drug: amifostine trihydrate
    4. Drug: carboplatin
    label
    Arm IV (carboplain, cisplatin, amifostine)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm I (cisplatin, vincristine sulfate, fluorouracil)
    2. Arm II (cisplatin, vincristine, fluorouracil, amifostine)
    3. Arm III (carboplatin, cisplatin)
    4. Arm IV (carboplain, cisplatin, amifostine)
    description
    Undergo surgical resection
    name
    therapeutic conventional surgery
    type
    PROCEDURE
  2. arm Group Labels
    1. Arm I (cisplatin, vincristine sulfate, fluorouracil)
    2. Arm II (cisplatin, vincristine, fluorouracil, amifostine)
    3. Arm III (carboplatin, cisplatin)
    4. Arm IV (carboplain, cisplatin, amifostine)
    description
    Given IV
    name
    cisplatin
    other Names
    1. CACP
    2. CDDP
    3. CPDD
    4. DDP
    type
    DRUG
  3. arm Group Labels
    1. Arm I (cisplatin, vincristine sulfate, fluorouracil)
    2. Arm II (cisplatin, vincristine, fluorouracil, amifostine)
    description
    Given IV
    name
    vincristine sulfate
    other Names
    1. leurocristine sulfate
    2. VCR
    3. Vincasar PFS
    type
    DRUG
  4. arm Group Labels
    1. Arm I (cisplatin, vincristine sulfate, fluorouracil)
    2. Arm II (cisplatin, vincristine, fluorouracil, amifostine)
    description
    Given IV
    name
    fluorouracil
    other Names
    1. 5-fluorouracil
    2. 5-Fluracil
    3. 5-FU
    type
    DRUG
  5. arm Group Labels
    1. Arm II (cisplatin, vincristine, fluorouracil, amifostine)
    2. Arm IV (carboplain, cisplatin, amifostine)
    description
    Given IV
    name
    amifostine trihydrate
    other Names
    1. ethiofos
    2. Ethyol
    3. gammaphos
    4. WR-2721
    type
    DRUG
  6. arm Group Labels
    1. Arm III (carboplatin, cisplatin)
    2. Arm IV (carboplain, cisplatin, amifostine)
    description
    Given IV
    name
    carboplatin
    other Names
    1. Carboplat
    2. CBDCA
    3. JM-8
    4. Paraplat
    5. Paraplatin
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
277
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    EFS rates will be estimated using the method of Kaplan and Meier. Survival curves will be compared using stratified logrank tests.
    measure
    Event-free survival (EFS) rates
    time Frame
    Up to 8 years
  2. description
    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.
    measure
    Toxicity rates assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC)
    time Frame
    Up to 8 years
Full 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.
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.
Source references
Source notices and limitations
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        er complete resection.[<a href="#cit/section_7.81">81</a>,<a href="#cit/section_7.82">82</a>] </li></ul></div></li><li>In a COG study (<a href="/clinicaltrials/NCT00003994">COG-P9645</a>), 16 patients with well-differentiated fetal histology hepatoblastoma with two or fewer mitoses per 10 high-power fields were not treated with c
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        1842"><li>At a median follow-up of 5.1 years, the EFS and OS rates were 100% for all nine children.</li></ul></div></li><li>In the COG <a href="/clinicaltrials/NCT00003994">P9645 (NCT00003994)</a> study, 16 patients with stage I (completely resected) tumors had well-differentiated fetal histology and received no adjuvant chemothe
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        n follow-up of 5.1 years, the EFS and OS rates were 100% for all nine children.</li></ul></div></li><li>In the COG <a href="/clinicaltrials/NCT00003994">P9645 (NCT00003994)</a> study, 16 patients with stage I (completely resected) tumors had well-differentiated fetal histology and received no adjuvant chemotherapy. In a retrospec
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        with hepatoblastoma encouraged resection at the time of diagnosis for all tumors amenable to resection without undue risk. The study (<a href="/clinicaltrials/NCT00003994">COG-P9645</a>) did not treat children with stage I tumors of well-differentiated fetal histology with preoperative or postoperative chemotherapy unless they d
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      source title
      Childhood Liver Cancer Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: January 6, 2025
        datetime
        2025-01-06T12:00:00Z
        display
        January 6, 2025

    Preserved source evidence · Not medical advice