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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00980460




Registration number
NCT00980460
Ethics application status
Date submitted
18/09/2009
Date registered
21/09/2009
Date last updated
21/10/2024

Titles & IDs
Public title
Risk-Based Therapy in Treating Younger Patients With Newly Diagnosed Liver Cancer
Scientific title
Treatment of Children With All Stages of Hepatoblastoma With Temsirolimus (NSC#683864) Added to High Risk Stratum Treatment
Secondary ID [1] 0 0
NCI-2011-01975
Secondary ID [2] 0 0
NCI-2011-01975
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PRETEXT I Hepatoblastoma 0 0
PRETEXT II Hepatoblastoma 0 0
PRETEXT III Hepatoblastoma 0 0
PRETEXT IV Hepatoblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cisplatin
Treatment: Drugs - Dexrazoxane
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Fluorouracil
Treatment: Drugs - Irinotecan Hydrochloride
Other interventions - Laboratory Biomarker Analysis
Treatment: Surgery - Liver Transplantation
Treatment: Drugs - Temsirolimus
Treatment: Surgery - Therapeutic Conventional Surgery
Treatment: Drugs - Vincristine Sulfate

Experimental: High-risk group (regimen H) - Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

Experimental: High-risk group (regimen W) - (regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity.

Experimental: Intermediate-risk group (regimen F) - Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. (Closed to accrual as of 3/12/2012)

Experimental: Low-risk group (regimen T) - Patients undergo surgery and then receive adjuvant cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, and vincristine sulfate IV over 1 minute on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Very low-risk group - Patients undergo surgery and then receive no further treatment.


Treatment: Drugs: Cisplatin
Given IV

Treatment: Drugs: Dexrazoxane
Given IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Fluorouracil
Given IV

Treatment: Drugs: Irinotecan Hydrochloride
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Surgery: Liver Transplantation
Undergo liver transplant

Treatment: Drugs: Temsirolimus
Given IV

Treatment: Surgery: Therapeutic Conventional Surgery
Undergo surgery

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival
Timepoint [1] 0 0
Time from patient enrollment to progression, treatment failure, death from any cause, diagnosis of a second malignant neoplasm, or last follow-up, assessed up to 5 years
Primary outcome [2] 0 0
Number of Cycles on Which Grade 3 or Higher Adverse Events Coded According to CTC AE Version 5 Were Observed
Timepoint [2] 0 0
During protocol therapy up to 1 year after enrollment
Primary outcome [3] 0 0
Number of Deaths
Timepoint [3] 0 0
During protocol therapy or within 30 days of the termination of protocol therapy up to 1 year after enrollment
Primary outcome [4] 0 0
Disease Status at the End of 2 Courses of Therapy
Timepoint [4] 0 0
First two cycles of therapy- up to 42 days after enrollment
Secondary outcome [1] 0 0
Feasibility of Referral for Liver Transplantation
Timepoint [1] 0 0
3 cycles of therapy - up to 3 months after enrollment

Eligibility
Key inclusion criteria
* Patients must be newly diagnosed with histologically-proven hepatoblastoma
* In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled on AHEP0731 without a biopsy

* Clinical situations in which such emergent treatment may be indicated include, but are not limited to, the following circumstances:

* Anatomic or mechanical compromise of critical organ function by tumor (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc)
* Uncorrectable coagulopathy
* For a patient to maintain eligibility for AHEP0731 when emergent treatment is given, the following must occur:

* The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alpha fetoprotein, and must meet all AHEP0731 eligibility criteria at the time of emergent treatment
* Patient must be enrolled on AHEP0731 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP0731 enrollment
* If the patient receives AHEP0731 chemotherapy PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
* Patients will be staged for risk classification and treatment at diagnosis using Children's Oncology Group (COG) staging guidelines
* At the time of study enrollment, the patient's treatment regimen must be identified; if the patient's primary tumor was resected prior to the day of enrollment and a blood specimen for the determination of serum alpha fetoprotein was not obtained prior to that surgery, the patient will be considered to have alpha fetoprotein of greater than 100 ng/mL for the purpose of treatment assignment; if tumor samples obtained prior to the date of enrollment were not sufficient to determine whether small cell undifferentiated (SCU) histology was present, treatment assignment will be made assuming SCU is not present in the tumor
* For patients with stage I or II disease, specimens for rapid central review have been submitted and the rapid central review diagnosis and staging must be available to be provided on the AHEP0731 eligibility case report form (CRF)
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
* Patients may have had surgical resection of some or all sites of hepatoblastoma prior to enrollment
* Organ function requirements are not required for enrolled patients who are stage I, PFH and will not be receiving chemotherapy
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR serum creatinine based on age/gender as follows:

* 1 month to < 6 months: 0.4 mg/dL
* 6 months to < 1 year: 0.5 mg/dL
* 1 to < 2 years: 0.6 mg/dL
* 2 to < 6 years: 0.8 mg/dL
* 6 to < 10 years: 1 mg/dL
* 10 to < 13 years: 1.2 mg/dL
* 13 to < 16 years: 1.5 mg/dL (male) or 1.4 mg/dL (female)
* >= 16 years: 1.7 mg/dL (male) or 1.4 mg/dL (female)
* Total bilirubin < 1.5 x upper limit of normal (ULN) for age
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN for age
* Absolute neutrophil count (ANC) > 750/uL
* Platelet count > 75,000/uL
* Shortening fraction >= 27% by echocardiogram
* Ejection fraction >= 47% by radionuclide angiogram (multi gated acquisition scan [MUGA]); Note: the echocardiogram (or MUGA) may be done within 28 days prior to enrollment
* Serum triglyceride level =< 300 mg/dL (=< 3.42 mmol/L)
* Serum cholesterol level =< 300 mg/dL (7.75 mmol/L)
* Random or fasting blood glucose within the upper normal limits for age; if the initial blood glucose is a random sample that is outside of the normal limits, then a follow-up fasting blood glucose can be obtained and must be within the upper normal limits for age
* Normal pulmonary function tests (including diffusing capacity of the lungs for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen); Note: for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
* Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and if seizures are well controlled
* Prothrombin time (PT) < 1.2 x ULN
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Minimum age
No limit
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with stage I or II disease who do not have specimens submitted for rapid central pathology review by day 14 after initial surgical resection
* Patients that have been previously treated with chemotherapy for hepatoblastoma or other hepatoblastoma-directed therapy (e.g., radiation therapy, biologic agents, local therapy [embolization, radiofrequency ablation, laser]) are not eligible
* Patients who have received any prior chemotherapy are not eligible
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anticancer agents are not eligible
* Patients who have previously received a solid organ transplant are not eligible
* Patients who have an uncontrolled infection are not eligible
* Females who are pregnant or breast feeding are not eligible for this study
* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
* Males and females of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method
* Patients receiving corticosteroids are not eligible; patients must have been off corticosteroids for 7 days prior to start of chemotherapy
* Patients who are currently receiving enzyme inducing anticonvulsants are not eligible
* Patients must not be receiving any of the following potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors: erythromycin, clarithromycin, azithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, grapefruit juice or St. John's wort
* Patients who are currently receiving therapeutic anticoagulants (including aspirin, low molecular weight heparin, warfarin and others) are not eligible
* Patients who are currently receiving angiotensin-converting enzymes (ACE) inhibitors are not eligible
* Patients must not have had major surgery within 6 weeks prior to enrollment on the high risk stratum; patients with history of recent minor surgical procedures (vascular catheter placement, bone marrow evaluation, laparoscopic surgery, liver tumor biopsy) will be eligible

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/09/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
5/03/2025
Actual
Sample size
Target
Accrual to date
Final
236
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [4] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
5006 - North Adelaide
Recruitment postcode(s) [4] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
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Hawaii
Country [12] 0 0
United States of America
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Idaho
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United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Iowa
Country [16] 0 0
United States of America
State/province [16] 0 0
Kentucky
Country [17] 0 0
United States of America
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Louisiana
Country [18] 0 0
United States of America
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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United States of America
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Missouri
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Nebraska
Country [26] 0 0
United States of America
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Nevada
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United States of America
State/province [27] 0 0
New Hampshire
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New Jersey
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New Mexico
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United States of America
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New York
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United States of America
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North Carolina
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Ohio
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Oklahoma
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Oregon
Country [35] 0 0
United States of America
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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United States of America
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Tennessee
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Texas
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Utah
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Virginia
Country [43] 0 0
United States of America
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Washington
Country [44] 0 0
United States of America
State/province [44] 0 0
West Virginia
Country [45] 0 0
United States of America
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Wisconsin
Country [46] 0 0
Brazil
State/province [46] 0 0
Sao Paulo
Country [47] 0 0
Canada
State/province [47] 0 0
Alberta
Country [48] 0 0
Canada
State/province [48] 0 0
British Columbia
Country [49] 0 0
Canada
State/province [49] 0 0
Manitoba
Country [50] 0 0
Canada
State/province [50] 0 0
Nova Scotia
Country [51] 0 0
Canada
State/province [51] 0 0
Ontario
Country [52] 0 0
Canada
State/province [52] 0 0
Quebec
Country [53] 0 0
Canada
State/province [53] 0 0
Saskatchewan
Country [54] 0 0
Japan
State/province [54] 0 0
Fukushima Prefecture
Country [55] 0 0
Japan
State/province [55] 0 0
Kagoshima
Country [56] 0 0
Japan
State/province [56] 0 0
Suntou
Country [57] 0 0
Japan
State/province [57] 0 0
Tokyo
Country [58] 0 0
Japan
State/province [58] 0 0
Hiroshima City
Country [59] 0 0
Puerto Rico
State/province [59] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Howard M Katzenstein
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00980460