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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04322318




Registration number
NCT04322318
Ethics application status
Date submitted
17/03/2020
Date registered
26/03/2020
Date last updated
22/04/2024

Titles & IDs
Public title
A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
Scientific title
Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT)
Secondary ID [1] 0 0
NCI-2020-01561
Secondary ID [2] 0 0
AREN1921
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaplastic Kidney Wilms Tumor 0 0
Recurrent Kidney Wilms Tumor 0 0
Stage II Kidney Wilms Tumor 0 0
Stage III Kidney Wilms Tumor 0 0
Stage IV Kidney Wilms Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Biopsy
Treatment: Surgery - Biospecimen Collection
Treatment: Surgery - Bone Scan
Treatment: Drugs - Carboplatin
Treatment: Surgery - Computed Tomography
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Etoposide
Treatment: Drugs - Ifosfamide
Treatment: Drugs - Irinotecan
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Surgery - Positron Emission Tomography
Treatment: Other - Radiation Therapy
Treatment: Surgery - Surgical Procedure
Treatment: Drugs - Topotecan
Treatment: Surgery - Transabdominal Ultrasound
Treatment: Drugs - Vincristine
Treatment: Surgery - X-Ray Imaging

Experimental: Arm I (Regimen UH-3) - See outline in detailed description section.

Experimental: Arm II (Regimen ICE/Cyclo/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.
Patients undergo surgery and/or RT during cycles 4, 7, and 10 as clinically indicated. Patients undergo a CT scan, a PET scan, a chest x-ray, MRI, an abdominal ultrasound, and/or a bone scan throughout the trial. Patients may also undergo blood specimen collection and biopsy throughout the trial.


Treatment: Surgery: Biopsy
Undergo a biopsy

Treatment: Surgery: Biospecimen Collection
Undergo blood sample collection

Treatment: Surgery: Bone Scan
Undergo a bone scan

Treatment: Drugs: Carboplatin
Given IV

Treatment: Surgery: Computed Tomography
Undergo a CT scan

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Doxorubicin
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Drugs: Ifosfamide
Given IV

Treatment: Drugs: Irinotecan
Given IV

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Surgery: Positron Emission Tomography
Undergo a PET scan

Treatment: Other: Radiation Therapy
Undergo RT

Treatment: Surgery: Surgical Procedure
Undergo surgery

Treatment: Drugs: Topotecan
Given IV

Treatment: Surgery: Transabdominal Ultrasound
Undergo abdominal ultrasound

Treatment: Drugs: Vincristine
Given IV

Treatment: Surgery: X-Ray Imaging
Undergo a chest x-ray
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free survival (EFS)
Timepoint [1] 0 0
From study entry to the earliest of relapse or disease progression, second malignant neoplasm, or death from any cause, assessed up to 5 years after study enrollment
Secondary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
From study entry to death due to any cause, assessed up to 5 years after study enrollment

Eligibility
Key inclusion criteria
- Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be
enrolled on AREN03B2 and have received an initial risk assignment showing DAWT (if
anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a
delayed nephrectomy classification showing DAWT (if anaplasia first noted at delayed
nephrectomy) prior to enrollment on AREN1921. Prior enrollment on AREN03B2 is not an
eligibility requirement for patients with relapsed favorable histology Wilms tumor.

- Patients must be =< 30 years old at study enrollment

- Patients with the following diagnoses are eligible for this study:

- Newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor as confirmed by
central review

- Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must
have previously achieved remission for their initial FHWT diagnosis to be
eligible for this study. The relapse risk groups are defined as follows,
regardless of radiation therapy:

- Standard-Risk relapse: Patients who received two chemotherapy agents for
frontline therapy; primarily actinomycin D and vincristine

- High-Risk relapse: Patients who received three chemotherapy agents for
frontline therapy; primarily vincristine, actinomycin D and doxorubicin or
vincristine, actinomycin D and irinotecan

- Very High-Risk relapse: Patients who received four or more chemotherapy
agents as part of initial therapy; primarily regimen M or its variations

- Patients with newly diagnosed DAWT must have had histologic verification of the
malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but
not required

- Note: For relapsed FHWT patients, an institutional pathology report confirming
favorable histology Wilms tumor (from relapse, if available, or from original
diagnosis) must be available for upload prior to initiation of protocol therapy

- Patients with newly diagnosed Stages 2 - 4 diffuse anaplastic Wilms tumor must be
enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure
that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or
delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior
therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse
anaplastic Wilms tumor at subsequent review of the initial biopsy

- Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least
1 lymph node sampled prior to study enrollment

- Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age

- Patients must have a life expectancy of >= 8 weeks

- Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have
had no prior systemic therapy, except in the following situations:

- Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks
of pre nephrectomy chemotherapy for what was originally presumed to be favorable
histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms
tumor at delayed nephrectomy

- Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of
chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for
presumed favorable histology Wilms tumor based on institutional review, but
subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2
initial risk assignment results (if available per current version of AREN03B2)

- Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an
emergent basis and within allowed timing as described

- Note: Patients who received prior therapy for presumed favorable histology Wilms
tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must
begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who
received emergency radiation to preserve organ function are eligible as noted.
Patients who received radiation as part of standard of care for presumed newly
diagnosed favorable histology Wilms tumor, along with chemotherapy as noted
above, prior to identification of diffuse anaplasia, are also eligible

- Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior
chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In
addition, patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study

- Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry
onto this study

- Radiation therapy (RT): >= 2 weeks (wks) must have elapsed for local palliative
RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >=
50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone
marrow (BM) radiation. Patients with relapsed favorable histology Wilms tumor who
received emergency radiation to preserve organ function are eligible and do not
need to washout with the above criteria

- Patients may not be receiving any other investigational agents (within 4 weeks prior
to study enrollment)

- Peripheral absolute neutrophil count (ANC) >= 750/uL (performed within 7 days prior to
enrollment)

- Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior
to enrollment)

- Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed
within 7 days prior to enrollment)

- Patients with high-risk or very high-risk relapsed FHWT who will be treated with
regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or
radioisotope glomerular filtration rate (GFR) and meet the following requirement:

- Creatinine clearance or radioisotope GFR >= 60 mL/min/1.73 m^2 (performed within
7 days prior to enrollment)

- Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be
treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR
(meeting the above criteria of GFR >= 60 mL/min/1.73 m^2), or an adequate serum
creatinine as per the following table:

- Age: Maximum Serum Creatinine (mg/dL)

- 1 month to < 6 months: 0.4 (male and female)

- 6 months to < 1 year: 0.5 (male and female)

- 1 to < 2 years: 0.6 (male and female)

- 2 to < 6 years: 0.8 (male and female)

- 6 to < 10 years: 1 (male and female)

- 10 to < 13 years: 1.2 (male and female)

- 13 to < 16 years: 1.5 (male), 1.4 (female)

- >= 16 years: 1.7 (male), 1.4 (female)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =<
ULN for patients whose total bilirubin > 1.5 x ULN (performed within 7 days prior to
enrollment)

- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age or =< 5 x ULN for patients with liver metastases
(performed within 7 days prior to enrollment)

- Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by
radionuclide angiogram (obtained within 21 days prior to enrollment and start of
protocol therapy)
Minimum age
No limit
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with a history of bilateral Wilms tumor (synchronous or metachronous)

- Patients with any uncontrolled, intercurrent illness including, but not limited to,
ongoing or active infection, or symptomatic congestive heart failure (defined as grade
2 or higher heart failure per Common Terminology Criteria for Adverse Events [CTCAE]
version 5.0)

- Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk
FHWT initially observed without chemotherapy) or received only one chemotherapy agent
for frontline therapy

- For patients with high-risk or very high-risk relapsed FHWT:

- Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate < 16
mmol/L and serum phosphate =< 2 mg/dL (or < 0.8 mmol/L) without supplementation

- For stages 2-4 DAWT and standard-risk relapsed FHWT patients:

- Chronic inflammatory bowel disease and/or bowel obstruction

- Concomitant use of St. John's wort, which cannot be stopped prior to the start of
trial treatment

- Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential

- Lactating females who plan to breastfeed their infants

- Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation

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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2027
Actual
Sample size
Target
221
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [5] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [6] 0 0
Monash Medical Center-Clayton Campus - Clayton
Recruitment hospital [7] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [8] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5006 - North Adelaide
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3052 - Parkville
Recruitment postcode(s) [8] 0 0
6009 - Perth
Recruitment outside Australia
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Alabama
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Alaska
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Wisconsin
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Alberta
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British Columbia
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Canada
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Manitoba
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Newfoundland and Labrador
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Nova Scotia
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Auckland
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Christchurch
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Puerto Rico
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Caguas
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San Juan
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Saudi Arabia
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Riyadh

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This phase II trial studies how well combination chemotherapy works in treating patients with
newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology
Wilms tumors (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 tumor 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 website
https://clinicaltrials.gov/ct2/show/NCT04322318
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James I Geller
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04322318