Vincristine, Dactinomycin, and Cyclophosphamide With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Low-Risk Rhabdomyosarcoma

Adult Rhabdomyosarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00075582
• Other study ID #: ARST0331
• Secondary ID: NCI-2009-00425CO
• Status: Completed
• Phase: Phase 3
• Start date: September 4, 2004
• Est. completion date: September 30, 2021

Study information

• Verified date: November 2021
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 390
• Est. completion date: September 30, 2021
• Est. primary completion date: August 13, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Adult Rhabdomyosarcoma
• Embryonal Childhood Rhabdomyosarcoma
• Embryonal-botryoid Childhood Rhabdomyosarcoma
• Previously Untreated Childhood Rhabdomyosarcoma
• Rhabdomyosarcoma

Intervention

Procedure:
• conventional surgery
Some patients may undergo second-look surgery

Drug:
• dactinomycin
Given IV
• cyclophosphamide
Given IV
• vincristine sulfate
Given IV

Radiation:
• radiation therapy
Undergo radiotherapy

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Sydney Children's Hospital	Randwick	New South Wales
Australia	The Children's Hospital at Westmead	Sydney	New South Wales
Australia	Sydney West Area Health Service-Westmead Hospital	Westmead	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Chedoke-McMaster Hospitals	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Hospital Sainte-Justine	Montreal	Quebec
Canada	The Montreal Children's Hospital of the MUHC	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Janeway Child Health Centre	Saint John's	Newfoundland and Labrador
Canada	Centre Hospitalier Universitaire de Quebec	Ste-Foy	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Starship Children's Hospital	Grafton	Auckland
Puerto Rico	San Jorge Children's Hospital	Santurce
Switzerland	Swiss Pediatric Oncology Group - Geneva	Geneva
Switzerland	Swiss Pediatric Oncology Group - Lausanne	Lausanne
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Oncology Group	Arcadia	California
United States	Mission Hospitals Inc	Asheville	North Carolina
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont	Burlington	Vermont
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston	Charleston	West Virginia
United States	Presbyterian Hospital	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	T C Thompson Children's Hospital	Chattanooga	Tennessee
United States	Childrens Memorial Hospital	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	The Children's Medical Center of Dayton	Dayton	Ohio
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
United States	Raymond Blank Children's Hospital	Des Moines	Iowa
United States	Wayne State University	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Hurley Medical Center	Flint	Michigan
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Greenville Cancer Treatment Center	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Hershey Children's Hospital	Hershey	Pennsylvania
United States	Memorial Healthcare System - Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic - Jacksonville	Jacksonville	Florida
United States	The Childrens Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Michigan State University - Breslin Cancer Center	Lansing	Michigan
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Miller Children's Hospital	Long Beach	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Children's Hospital Central California	Madera	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Baptist Hospital of Miami	Miami	Florida
United States	Miami Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	UMDNJ - Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York
United States	Children's Hospital-Main Campus	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Childrens Hospital-King's Daughters	Norfolk	Virginia
United States	Advocate Hope Children's Hospital	Oak Lawn	Illinois
United States	Children's Hospital and Research Center at Oakland	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Childrens Hospital of Orange County	Orange	California
United States	M D Anderson Cancer Center- Orlando	Orlando	Florida
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Nemours Children's Clinic - Pensacola	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	University of California San Francisco Medical Center-Parnassus	San Francisco	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Maine Children's Cancer Program	Scarborough	Maine
United States	Seattle Children's Hospital	Seattle	Washington
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Southern Illinois University	Springfield	Illinois
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Saint Joseph Children's Hospital of Tampa	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	University of Arizona Health Sciences Center	Tucson	Arizona
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  Puerto Rico,  Switzerland, 

References & Publications (1)

Woolson RF (1981) Rank-tests and a one-sample log-rank test for comparing observed survival-data to a standard population. Biometrics 37: 687-696.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients With Low-risk Rhabdomyosarcoma in Subset 1 Failure Free at 5 Years Following Study Entry	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.	From enrollment up to 5 years
Primary	Percentage of Patients With Stage 1, Clinical Group IIB or C (Node Positive) or Stage 2 Failure Free at 5 Years Following Study Entry	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.	From enrollment up to 5 years
Primary	Percentage of Patients With Low-risk Rhabdomyosarcoma in Subset 2 Failure Free at 5 Years Following Study Entry	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.	From enrollment up to 5 years
Secondary	Cumulative Incidence of Patients Who Receive Reduced Doses of Radiation Therapy	The local failure rate will be estimated using cumulative incidence curves.	From enrollment up to 5 years
Secondary	Percentage of Patients With Delayed Surgical Procedures	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.	At 13 weeks after induction
Secondary	Cumulative Incidence of Group III Patients Who Received With Reduced Radiotherapy Dose	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.	From enrollment up to 20 weeks

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive