Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor
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| ClinicalTrials.gov Identifier: NCT00352534 |
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Recruitment Status :
Active, not recruiting
First Posted : July 14, 2006
Results First Posted : May 15, 2017
Last Update Posted : January 31, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Stage I Kidney Wilms Tumor Stage II Kidney Wilms Tumor Stage III Kidney Wilms Tumor | Radiation: 3-Dimensional Conformal Radiation Therapy Biological: Dactinomycin Drug: Doxorubicin Hydrochloride Procedure: Therapeutic Conventional Surgery Drug: Vincristine Sulfate | Phase 3 |
PRIMARY OBJECTIVES:
I. Evaluate the overall and event-free survival of younger patients with newly diagnosed stage I favorable histology Wilms' tumor (< 2 years of age and < 550gms) treated with nephrectomy only (very low risk), or with newly diagnosed stage III favorable histology Wilms tumor with possible nephrectomy followed by vincristine, dactinomycin, doxorubicin hydrochloride, and radiotherapy (standard risk).
SECONDARY OBJECTIVES:
I. Determine the effects of adding doxorubicin hydrochloride to the regimen for patients with stage I or II favorable histology found to have a high-risk biological marker.
II. Determine whether the omission of adjuvant therapy increases the incidence of contralateral kidney lesions in patients with very low-risk disease treated by nephrectomy and observation only.
III. Determine whether the omission of adjuvant therapy increases the incidence of renal failure in patients with very low-risk disease who have metachronous relapse.
IV. Correlate study outcomes in patients with standard-risk disease with biological data from tissue collections on protocol study COG-AREN03B2.
OUTLINE: This is a multicenter study. Patients are stratified according to clinical and biological risk factors (very low risk vs standard risk).
STRATUM I: (very low-risk disease) Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks.
STRATUM II: (standard-risk, stage I or II disease with adverse biological marker) Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.
STRATUM III: (standard-risk, stage III disease) Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks.
After completion of study treatment, patients are followed periodically for up to 8 years.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 808 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Treatment for Very Low and Standard Risk Favorable Histology Wilms Tumor |
| Actual Study Start Date : | October 30, 2006 |
| Actual Primary Completion Date : | December 31, 2014 |
| Estimated Study Completion Date : | December 31, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Stratum I (very low-risk disease)
Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Patients undergo radiotherapy
Other Names:
Biological: Dactinomycin Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo surgery Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Stratum II (standard-risk, stage I or II)
Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Patients undergo radiotherapy
Other Names:
Biological: Dactinomycin Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo surgery Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Stratum III (standard-risk, stage III)
Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Patients undergo radiotherapy
Other Names:
Biological: Dactinomycin Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo surgery Drug: Vincristine Sulfate Given IV
Other Names:
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- Event Free Survival Probability [ Time Frame: 4 years ]Probability of no relapse, secondary malignancy, or death after 4 year in the study.
- Overall Survival (OS) Probability [ Time Frame: 4 years ]Probability of being alive after 4 years in the study.
- Incidence of Contralateral Kidney Lesions [ Time Frame: During follow-up ]Number of contralateral kidney lesions during follow-up.
- Incidence of Renal Failure [ Time Frame: During follow-up ]Number of renal failures defined as requiring dialysis or renal transplant as determined by low GFR during follow-up
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| Ages Eligible for Study: | up to 29 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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Histologically confirmed Wilms' tumor
- Newly diagnosed stage I-III disease
- Favorable histology
- No moderate- or high-risk Wilms' predisposition syndromes
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Must meet 1 of the following disease stratification categories:
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Very low-risk disease
- Stage I disease
- Age < 2 years
- Tumor weight < 550 g
- Regional lymph nodes histologically negative (must have been sampled)
- No pulmonary metastases on CT scan of chest
- No synchronous bilateral Wilms tumors (Stage V)
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Not predisposed to develop bilateral Wilms tumors, defined as unilateral Wilms tumor and any of the following:
- Aniridia
- Beckwith-Wiedemann syndrome
- Simpson-Golabi-Behmel syndrome
- Denys-Drash syndrome or other associated genito-urinary anomalies
- Multicentric WT or unilateral WT with contralateral nephrogenic rest(s) in a child < 1 year of age
- Diffuse hyperplastic perilobar nephroblastomatosis
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Standard-risk disease meeting 1 of the following criteria:
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Disease does not require radiotherapy
- LOH at chromosomes 1p and 16q for stage I or II
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Stage I disease meeting 1 of the following criteria:
- Age ≥ 2 years to age < 30 years
- Tumor weight ≥ 500 g
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Stage II disease
- Age < 30 years
- Any tumor weight
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Disease requires radiotherapy
- No LOH at chromosomes 1p and 16q*
- Stage III disease
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- Must be enrolled on protocol COG-AREN03B2
- Karnofsky performance status (PS) 50-100% for patients > 16 years old
- Lansky PS 50-100% for patients ≤ 16 years old
- Bilirubin (direct) ≤ 1.5 times upper limit of normal (ULN)
- AST or ALT < 2.5 times ULN
- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram (standard-risk disease)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patient must use effective contraception
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No prior tumor-directed chemotherapy or radiotherapy
- Patients transferring from AREN03B2 with LOH 1p and 16q allowed
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00352534
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| Principal Investigator: | Conrad V Fernandez | Children's Oncology Group |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00352534 |
| Other Study ID Numbers: |
AREN0532 NCI-2009-01067 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 06-936 AREN0532 CDR0000487540 AREN0532 ( Other Identifier: Children's Oncology Group ) AREN0532 ( Other Identifier: CTEP ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | July 14, 2006 Key Record Dates |
| Results First Posted: | May 15, 2017 |
| Last Update Posted: | January 31, 2023 |
| Last Verified: | January 2023 |
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Neoplasms Wilms Tumor Neoplasms, Complex and Mixed Neoplasms by Histologic Type Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Neoplastic Syndromes, Hereditary Kidney Diseases Urologic Diseases Genetic Diseases, Inborn Dactinomycin Cactinomycin Doxorubicin |
Liposomal doxorubicin Vincristine Antibiotics, Antineoplastic Antineoplastic Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Anti-Bacterial Agents Anti-Infective Agents Protein Synthesis Inhibitors |