Official Title
Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumours (DAWT) and Relapsed Favorable Histology Wilms Tumours (FHWT)
Summary:
This phase II trial studies how well combination chemotherapy works in treating patients with
newly diagnosed stage II-IV diffuse anaplastic Wilms tumours (DAWT) or favourable histology
Wilms tumours (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such
as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan)
and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) work
in different ways to stop the growth of tumour cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. This trial may help doctors find out
what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and
standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen
ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with
3 or more drugs for the initial WT).
Trial Description
Primary Outcome:
- Event-free survival (EFS)
Secondary Outcome:
PRIMARY OBJECTIVES:
-
To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/
carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the
event-free survival (EFS) of patients with newly diagnosed stage 4 diffuse anaplastic Wilms
tumour (DAWT) as compared to historical controls.
- To evaluate whether the addition of vincristine/irinotecan to
cyclophosphamide/carboplatin/etoposide alternating with
vincristine/doxorubicin/cyclophosphamide improves the EFS of patients with standard-risk
relapsed favourable histology Wilms tumour (SRrFHWT) as compared to historical controls.
SECONDARY OBJECTIVES:
-
To evaluate whether the addition of vincristine/irinotecan to
cyclophosphamide/carboplatin/etoposide alternating with
vincristine/doxorubicin/cyclophosphamide improves the overall survival (OS) of patients with
newly diagnosed stage 4 DAWT as compared to historical controls.
- To evaluate whether the addition of vincristine/irinotecan to
cyclophosphamide/carboplatin/etoposide alternating with
vincristine/doxorubicin/cyclophosphamide improves the OS of patients with SRrFHWT as compared
to historical controls.
- To evaluate whether the addition of vincristine/irinotecan to
cyclophosphamide/carboplatin/etoposide alternating with
vincristine/doxorubicin/cyclophosphamide improves the EFS and OS of patients with newly
diagnosed stage 2 and 3 DAWT as compared to historical controls.
- To establish EFS and OS for high-risk (HRrFHWT) and very high risk (VHRrFHWT) relapsed
favourable histology Wilms tumour treated with ifosfamide/carboplatin/etoposide alternating
with cyclophosphamide/ topotecan.
EXPLORATORY OBJECTIVES:
-
To describe renal toxicity of ifosfamide/carboplatin/etoposide in HRrFHWT and VHRrFHWT
patients using conventional and novel biomarkers of renal toxicity (urine NGAL, cystatin C
and Kim1) in the context of the chemotherapy regimens used on this study.
- To collect and bank serial blood and urine samples in patients with newly diagnosed DAWT
or relapsed FHWT and tumour tissue in patients with relapsed FHWT, for future analysis.
- To assess the impact of p53 gene and protein expression on outcome for patients with
newly diagnosed DAWT.
- To determine EFS/OS in the subsets of patients with newly diagnosed DAWT or relapsed FWHT
who undergo gross total resection at all disease sites at diagnosis or after neoadjuvant
chemotherapy.
- To describe the rate of regional lymph node sampling at the time of nephrectomy with the
use of a pre-operative surgical checklist for patients with newly diagnosed DAWT.
- To determine the feasibility of intensity modulated radiation therapy (IMRT) with central
quality assurance (QA) monitoring to reduce radiation induced toxicity to the heart, thyroid,
breast and solitary kidney for children with lung and liver metastases (part of an
overarching aim in this study and across frontline favourable histology Wilms tumour studies).
OUTLINE:
Patients are assigned to 1 of 2 arms.
ARM I (REGIMEN UH-3):
CYCLES 1, 5, 7, 10, AND 13: Patients receive vincristine intravenously (IV) over 1 minute or
via minibag per institutional policy on days 1, 8, and 15. Patients also receive doxorubicin
IV over 1-15 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats
every 21 days during cycles 1, 5, 7, 10, and 13 in the absence of disease progression or
unacceptable toxicity.
CYCLES 2, 6, 9, 12, AND 14: Patients receive carboplatin IV over 15-60 minutes on day 1.
Patients also receive cyclophosphamide IV over 15-30 minutes and etoposide IV over 1-2 hours
on days 1-4. Treatment repeats every 21 days during cycles 2, 6, 9, 12, and 14 in the absence
of disease progression or unacceptable toxicity.
CYCLES 3, 4, 8, AND 11: Patients receive vincristine IV over 1 minute or via minibag per
institutional policy on days 1 and 8 and irinotecan IV over 90 minutes on days 1-5. Treatment
repeats every 21 days during cycles 3, 4, 8, and 11 in the absence of disease progression or
unacceptable toxicity.
ARM II (REGIMEN IFOSFAMIDE, CARBOPLATIN, ETOPOSIDE [ICE]/CYCLOPHOSPHAMIDE [CYCLO]/TOPOTECAN
[TOPO]):
CYCLES 1, 2, 4, 5, 7, AND 9: Patients receive carboplatin IV over 15-60 minutes on day 1.
Patients also receive etoposide IV over 1-2 hours and ifosfamide IV over 2-4 hours on days
1-3. Treatment repeats every 21 days during cycles 1, 2, 4, 5, 7, and 9 in the absence of
disease progression or unacceptable toxicity.
CYCLES 3, 6, 8, AND 10: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan
IV over 30 minutes on days 1-5. Treatment repeats every 21 days during cycles 3, 6, 8, and 10
in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for years 1-2,
every 6 months for years 3-4, and once at year 5.
View this trial on ClinicalTrials.gov
