Brief Summary
This phase III trial is studying how well combination chemotherapy and radiation therapy work in treating patients with newly diagnosed low-risk rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine, dactinomycin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which treatment regimen is more effective in treating low-risk rhabdomyosarcoma.
Brief Title
Vincristine, Dactinomycin, and Cyclophosphamide With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Low-Risk Rhabdomyosarcoma
Detailed Description
PRIMARY OBJECTIVES:
I. Determine the failure-free survival of patients with newly diagnosed low-risk rhabdomyosarcoma treated with vincristine (V), dactinomycin (A), cyclophosphamide (C), and radiotherapy.
SECONDARY OBJECTIVES:
I. Determine local control rates in patients treated with this regimen. II. Determine the rate of second-look surgery in patients with bulk residual tumor at diagnosis (clinical group III) and the proportion of second-look surgeries that render patients treated with this regimen tumor-free or with microscopic tumor only and evaluate the pathologic significance of that residual tumor.
III. Determine the local control rates in patients with clinical group III disease treated with response-adjusted radiotherapy doses after second-look surgical resection.
OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 2 treatment regimens according to disease stage and clinical group.
REGIMEN I (subset 1 patients) \[closed to accrual as of 08/13/2010: Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21 and dactinomycin\* IV over 1 minute on day 1 of weeks 13, 16, 19, and 22; and radiotherapy\*\*, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose.
REGIMEN II (subset 2 patients)\[closed to accrual as of 9/23/2011\]: Patients receive VAC chemotherapy and radiotherapy\*\* as in regimen I and VA chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin\* IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46. Patients with clinical group III disease may undergo second-look surgery at week 13 followed by response-adjusted radiotherapy, and continued VA\* chemotherapy. In both regimens, treatment continues in the absence of disease progression or unacceptable toxicity.
NOTE: \*For both regimens, dactinomycin is omitted during radiotherapy.
NOTE: \*\*Clinical Group I tumors and those with Clinical Group III uterine/cervix primary disease with negative nodes who have undergone a complete resection (i.e. hysterectomy) at Week 13 do not receive radiotherapy at Week 13
Patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 1 year, and then annually thereafter.
I. Determine the failure-free survival of patients with newly diagnosed low-risk rhabdomyosarcoma treated with vincristine (V), dactinomycin (A), cyclophosphamide (C), and radiotherapy.
SECONDARY OBJECTIVES:
I. Determine local control rates in patients treated with this regimen. II. Determine the rate of second-look surgery in patients with bulk residual tumor at diagnosis (clinical group III) and the proportion of second-look surgeries that render patients treated with this regimen tumor-free or with microscopic tumor only and evaluate the pathologic significance of that residual tumor.
III. Determine the local control rates in patients with clinical group III disease treated with response-adjusted radiotherapy doses after second-look surgical resection.
OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 2 treatment regimens according to disease stage and clinical group.
REGIMEN I (subset 1 patients) \[closed to accrual as of 08/13/2010: Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21 and dactinomycin\* IV over 1 minute on day 1 of weeks 13, 16, 19, and 22; and radiotherapy\*\*, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose.
REGIMEN II (subset 2 patients)\[closed to accrual as of 9/23/2011\]: Patients receive VAC chemotherapy and radiotherapy\*\* as in regimen I and VA chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin\* IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46. Patients with clinical group III disease may undergo second-look surgery at week 13 followed by response-adjusted radiotherapy, and continued VA\* chemotherapy. In both regimens, treatment continues in the absence of disease progression or unacceptable toxicity.
NOTE: \*For both regimens, dactinomycin is omitted during radiotherapy.
NOTE: \*\*Clinical Group I tumors and those with Clinical Group III uterine/cervix primary disease with negative nodes who have undergone a complete resection (i.e. hysterectomy) at Week 13 do not receive radiotherapy at Week 13
Patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 1 year, and then annually thereafter.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Adult Rhabdomyosarcoma
Embryonal Childhood Rhabdomyosarcoma
Embryonal-botryoid Childhood Rhabdomyosarcoma
Previously Untreated Childhood Rhabdomyosarcoma
Eligibility Criteria
Inclusion Criteria:
* Histologically confirmed newly diagnosed embryonal rhabdomyosarcoma (RMS), botryoid or spindle cell variants of embryonal RMS, or embryonal ectomesenchymoma, meeting criteria for 1 of the following subsets:
* Subset 1, defined by meeting 1 of the following criteria (closed to accrual as of 08/13/2010):
* Stage 1 and clinical group I (completely resected) or II (microscopic residual disease and/or regional lymph node involvement) disease
* Stage 1 and clinical group III (gross residual disease) disease arising in the orbit
* Stage 2 and clinical group I or II disease
* Subset 2, defined by meeting 1 of the following criteria (closed to accrual as of 09/23/2011):
* Stage 1 and clinical group III disease arising in a non-orbit site
* Stage 3 and clinical group I or II disease
* Prior staging ipsilateral retroperitoneal lymph node dissection required for all patients age 10 and over with paratesticular tumors and patients under 10 years of age with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement is identified by imaging studies)
* If there is extensive gross node involvement only confirmatory node biopsy is recommended and the patient is classified as Clinical Group III
* Prior regional lymph node sampling required for patients with extremity tumors
* None of the following diagnoses:
* Intermediate-risk embryonal RMS
* Metastatic embryonal RMS
* Alveolar RMS
* Undifferentiated sarcoma
* RMS not otherwise specified (NOS)
* Other soft tissue sarcoma, including sarcoma NOS
* Prior enrollment on clinical trial COG-D9902
* Performance status - ECOG 0-2
* Performance status - Karnofsky 50-100% (≥ 16 years old)
* Performance status - Lansky 50-100% (\< 16 years old)
* Absolute neutrophil count at least 750/mm\^3
* Platelet count at least 75,000/mm\^3 (transfusion independent)
* Bilirubin no greater than 1.5 times upper limit of normal (ULN)\*
* Creatinine\* based on age/gender as follows:
* No greater than 0.8 mg/dL for patients age 5 and under
* No greater than 1.0 mg/dL for patients age 6 to 9
* No greater than 1.2 mg/dL for patients age 10 to 12
* No greater than 1.4 mg/dL for female patients age 13 and over
* No greater than 1.5 mg/dL for male patients age 13 to 15
* No greater than 1.7 mg/dL for male patients age 16 and over
* Creatinine clearance\* or radioisotope glomerular filtration rate at least 70 mL/min/1.73 m\^2
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled infection
* No prior chemotherapy (except for patients treated on the related intermediate-risk study)
* Prior steroids allowed
* No prior radiotherapy
* Histologically confirmed newly diagnosed embryonal rhabdomyosarcoma (RMS), botryoid or spindle cell variants of embryonal RMS, or embryonal ectomesenchymoma, meeting criteria for 1 of the following subsets:
* Subset 1, defined by meeting 1 of the following criteria (closed to accrual as of 08/13/2010):
* Stage 1 and clinical group I (completely resected) or II (microscopic residual disease and/or regional lymph node involvement) disease
* Stage 1 and clinical group III (gross residual disease) disease arising in the orbit
* Stage 2 and clinical group I or II disease
* Subset 2, defined by meeting 1 of the following criteria (closed to accrual as of 09/23/2011):
* Stage 1 and clinical group III disease arising in a non-orbit site
* Stage 3 and clinical group I or II disease
* Prior staging ipsilateral retroperitoneal lymph node dissection required for all patients age 10 and over with paratesticular tumors and patients under 10 years of age with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement is identified by imaging studies)
* If there is extensive gross node involvement only confirmatory node biopsy is recommended and the patient is classified as Clinical Group III
* Prior regional lymph node sampling required for patients with extremity tumors
* None of the following diagnoses:
* Intermediate-risk embryonal RMS
* Metastatic embryonal RMS
* Alveolar RMS
* Undifferentiated sarcoma
* RMS not otherwise specified (NOS)
* Other soft tissue sarcoma, including sarcoma NOS
* Prior enrollment on clinical trial COG-D9902
* Performance status - ECOG 0-2
* Performance status - Karnofsky 50-100% (≥ 16 years old)
* Performance status - Lansky 50-100% (\< 16 years old)
* Absolute neutrophil count at least 750/mm\^3
* Platelet count at least 75,000/mm\^3 (transfusion independent)
* Bilirubin no greater than 1.5 times upper limit of normal (ULN)\*
* Creatinine\* based on age/gender as follows:
* No greater than 0.8 mg/dL for patients age 5 and under
* No greater than 1.0 mg/dL for patients age 6 to 9
* No greater than 1.2 mg/dL for patients age 10 to 12
* No greater than 1.4 mg/dL for female patients age 13 and over
* No greater than 1.5 mg/dL for male patients age 13 to 15
* No greater than 1.7 mg/dL for male patients age 16 and over
* Creatinine clearance\* or radioisotope glomerular filtration rate at least 70 mL/min/1.73 m\^2
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled infection
* No prior chemotherapy (except for patients treated on the related intermediate-risk study)
* Prior steroids allowed
* No prior radiotherapy
Inclusion Criteria
Inclusion Criteria:
* Histologically confirmed newly diagnosed embryonal rhabdomyosarcoma (RMS), botryoid or spindle cell variants of embryonal RMS, or embryonal ectomesenchymoma, meeting criteria for 1 of the following subsets:
* Subset 1, defined by meeting 1 of the following criteria (closed to accrual as of 08/13/2010):
* Stage 1 and clinical group I (completely resected) or II (microscopic residual disease and/or regional lymph node involvement) disease
* Stage 1 and clinical group III (gross residual disease) disease arising in the orbit
* Stage 2 and clinical group I or II disease
* Subset 2, defined by meeting 1 of the following criteria (closed to accrual as of 09/23/2011):
* Stage 1 and clinical group III disease arising in a non-orbit site
* Stage 3 and clinical group I or II disease
* Prior staging ipsilateral retroperitoneal lymph node dissection required for all patients age 10 and over with paratesticular tumors and patients under 10 years of age with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement is identified by imaging studies)
* If there is extensive gross node involvement only confirmatory node biopsy is recommended and the patient is classified as Clinical Group III
* Prior regional lymph node sampling required for patients with extremity tumors
* None of the following diagnoses:
* Intermediate-risk embryonal RMS
* Metastatic embryonal RMS
* Alveolar RMS
* Undifferentiated sarcoma
* RMS not otherwise specified (NOS)
* Other soft tissue sarcoma, including sarcoma NOS
* Prior enrollment on clinical trial COG-D9902
* Performance status - ECOG 0-2
* Performance status - Karnofsky 50-100% (≥ 16 years old)
* Performance status - Lansky 50-100% (\< 16 years old)
* Absolute neutrophil count at least 750/mm\^3
* Platelet count at least 75,000/mm\^3 (transfusion independent)
* Bilirubin no greater than 1.5 times upper limit of normal (ULN)\*
* Creatinine\* based on age/gender as follows:
* No greater than 0.8 mg/dL for patients age 5 and under
* No greater than 1.0 mg/dL for patients age 6 to 9
* No greater than 1.2 mg/dL for patients age 10 to 12
* No greater than 1.4 mg/dL for female patients age 13 and over
* No greater than 1.5 mg/dL for male patients age 13 to 15
* No greater than 1.7 mg/dL for male patients age 16 and over
* Creatinine clearance\* or radioisotope glomerular filtration rate at least 70 mL/min/1.73 m\^2
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled infection
* No prior chemotherapy (except for patients treated on the related intermediate-risk study)
* Prior steroids allowed
* No prior radiotherapy
* Histologically confirmed newly diagnosed embryonal rhabdomyosarcoma (RMS), botryoid or spindle cell variants of embryonal RMS, or embryonal ectomesenchymoma, meeting criteria for 1 of the following subsets:
* Subset 1, defined by meeting 1 of the following criteria (closed to accrual as of 08/13/2010):
* Stage 1 and clinical group I (completely resected) or II (microscopic residual disease and/or regional lymph node involvement) disease
* Stage 1 and clinical group III (gross residual disease) disease arising in the orbit
* Stage 2 and clinical group I or II disease
* Subset 2, defined by meeting 1 of the following criteria (closed to accrual as of 09/23/2011):
* Stage 1 and clinical group III disease arising in a non-orbit site
* Stage 3 and clinical group I or II disease
* Prior staging ipsilateral retroperitoneal lymph node dissection required for all patients age 10 and over with paratesticular tumors and patients under 10 years of age with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement is identified by imaging studies)
* If there is extensive gross node involvement only confirmatory node biopsy is recommended and the patient is classified as Clinical Group III
* Prior regional lymph node sampling required for patients with extremity tumors
* None of the following diagnoses:
* Intermediate-risk embryonal RMS
* Metastatic embryonal RMS
* Alveolar RMS
* Undifferentiated sarcoma
* RMS not otherwise specified (NOS)
* Other soft tissue sarcoma, including sarcoma NOS
* Prior enrollment on clinical trial COG-D9902
* Performance status - ECOG 0-2
* Performance status - Karnofsky 50-100% (≥ 16 years old)
* Performance status - Lansky 50-100% (\< 16 years old)
* Absolute neutrophil count at least 750/mm\^3
* Platelet count at least 75,000/mm\^3 (transfusion independent)
* Bilirubin no greater than 1.5 times upper limit of normal (ULN)\*
* Creatinine\* based on age/gender as follows:
* No greater than 0.8 mg/dL for patients age 5 and under
* No greater than 1.0 mg/dL for patients age 6 to 9
* No greater than 1.2 mg/dL for patients age 10 to 12
* No greater than 1.4 mg/dL for female patients age 13 and over
* No greater than 1.5 mg/dL for male patients age 13 to 15
* No greater than 1.7 mg/dL for male patients age 16 and over
* Creatinine clearance\* or radioisotope glomerular filtration rate at least 70 mL/min/1.73 m\^2
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled infection
* No prior chemotherapy (except for patients treated on the related intermediate-risk study)
* Prior steroids allowed
* No prior radiotherapy
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
49 Years
NCT Id
NCT00075582
Org Class
Network
Org Full Name
Children's Oncology Group
Org Study Id
ARST0331
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Vincristine, Dactinomycin, and Lower Doses of Cyclophosphamide With or Without Radiation Therapy for Patients With Newly Diagnosed Low-Risk Embryonal/Botryoid/Spindle Cell Rhabdomyosarcoma
Primary Outcomes
Outcome Description
Kaplan Meier estimate of failure free survival at 5 years, where failure free survival is defined as the time to relapse, progression, second malignancy, and death whichever occurs first.
Outcome Measure
Percentage of Patients With Low-risk Rhabdomyosarcoma in Subset 1 Failure Free at 5 Years Following Study Entry
Outcome Time Frame
From enrollment up to 5 years
Outcome Description
Kaplan Meier estimate of failure free survival at 5 years, where failure free survival is defined as the time to relapse, progression, second malignancy, and death whichever occurs first.
Outcome Measure
Percentage of Patients With Stage 1, Clinical Group IIB or C (Node Positive) or Stage 2 Failure Free at 5 Years Following Study Entry
Outcome Time Frame
From enrollment up to 5 years
Outcome Description
Kaplan Meier estimate of failure free survival at 5 years, where failure free survival is defined as the time to relapse, progression, second malignancy, and death whichever occurs first.
Outcome Measure
Percentage of Patients With Low-risk Rhabdomyosarcoma in Subset 2 Failure Free at 5 Years Following Study Entry
Outcome Time Frame
From enrollment up to 5 years
Secondary Ids
Secondary Id
NCI-2009-00425
Secondary Id
COG-ARST0331
Secondary Id
CDR0000347078
Secondary Id
U10CA098543
Secondary Outcomes
Outcome Description
The local failure rate will be estimated using cumulative incidence curves.
Outcome Time Frame
From enrollment up to 5 years
Outcome Measure
Cumulative Incidence of Patients Who Receive Reduced Doses of Radiation Therapy
Outcome Description
The decision to perform second-look surgery should be based on the physical examination and imaging studies at Week 12 and should only be considered if a reasonable functional and cosmetic result is anticipated.
Outcome Time Frame
At 13 weeks after induction
Outcome Measure
Percentage of Patients With Delayed Surgical Procedures
Outcome Description
The local failure rate will be estimated using cumulative incidence curves for Group III patients who received reduced doses of radiation therapy after second look surgical resection.
Outcome Time Frame
From enrollment up to 20 weeks
Outcome Measure
Cumulative Incidence of Group III Patients Who Received With Reduced Radiotherapy Dose
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
49
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Peter Cole
Investigator Email
pcole@montefiore.org
Investigator Phone
718-839-7462