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High-Dose Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Metastatic Rhabdomyosarcoma or Ectomesenchymoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00354744
Recruitment Status : Completed
First Posted : July 20, 2006
Results First Posted : January 10, 2014
Last Update Posted : January 29, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Sarcoma
Interventions Biological: dactinomycin
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: irinotecan hydrochloride
Drug: vincristine sulfate
Procedure: conventional surgery
Radiation: radiation therapy
Biological: filgrastim
Enrollment 109
Recruitment Details  
Pre-assignment Details  
Arm/Group Title High_Risk_Rhabdomyosarcoma
Hide Arm/Group Description Parameningeal (without intracranial extension) and paraspinal tumors receive chemotherapy starting Week 1 and begin radiation therapy at Week 20. Weeks 1-6: vincristine sulfate and irinotecan hydrochloride. Weeks 7-34: vincristine sulfate and irinotecan hydrochloride, Cyclophosphamide with MESNA, Doxorubicin hydrochloride, Etoposide, Ifosfamide with MESNA. Weeks 35-54: vincristine sulfate, Dactinomycin, irinotecan hydrochloride and Cyclophosphamide with MESNA and Filgrastim. Radiation therapy beginning at Week 20. Second look conventional surgery: Surgical resection other than biopsy will be applicable for the majority of patients.
Period Title: Overall Study
Started 109
Completed 67
Not Completed 42
Reason Not Completed
Adverse Event             2
Death             2
Lack of Efficacy             11
Lost to Follow-up             2
Physician Decision             11
Withdrawal by Subject             14
Arm/Group Title High_Risk_Rhabdomyosarcoma
Hide Arm/Group Description Parameningeal (without intracranial extension) and paraspinal tumors receive chemotherapy starting Week 1 and begin radiation therapy at Week 20. Weeks 1-6: vincristine sulfate and irinotecan hydrochloride. Weeks 7-34: vincristine sulfate and irinotecan hydrochloride, Cyclophosphamide with MESNA, Doxorubicin hydrochloride, Etoposide, Ifosfamide with MESNA. Weeks 35-54: vincristine sulfate, Dactinomycin, irinotecan hydrochloride and Cyclophosphamide with MESNA and Filgrastim. Radiation therapy beginning at Week 20. Second look conventional surgery: Surgical resection other than biopsy will be applicable for the majority of patients.
Overall Number of Baseline Participants 109
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants
<=18 years
96
  88.1%
Between 18 and 65 years
13
  11.9%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 109 participants
11.85  (6.55)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants
Female
49
  45.0%
Male
60
  55.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants
Hispanic or Latino
18
  16.5%
Not Hispanic or Latino
86
  78.9%
Unknown or Not Reported
5
   4.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants
American Indian or Alaska Native
1
   0.9%
Asian
5
   4.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
16
  14.7%
White
76
  69.7%
More than one race
0
   0.0%
Unknown or Not Reported
11
  10.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 109 participants
United States 92
Canada 11
Australia 6
1.Primary Outcome
Title Number of Patients With Complete or Partial Response Assessed by RECIST Criteria
Hide Description Volumetric measurements of the primary tumor using an elliptical model (0.5 x the product of the 3 largest perpendicular diameters) to assess response to neoadjuvant therapy. The RECIST (Response Evaluation Criteria in Solid Tumors) from the NCI will be used for assessment of the size of measurable metastases, including nodal metastases. Primary Tumor Measurement: Technical guidelines for cross-sectional imaging computed tomography (CT) slice thickness should be 5mm or less and the diameter of the "measurable" mass should be at least twice the reconstructed slice thickness. Smaller masses are considered detectable, but will be counted as "non-measurable." Complete Response (CR): Complete disappearance of the tumor confirmed at >4 weeks. Partial Response (PR): At least 64% decrease in volume compared to the measurement obtained at study enrollment. Progressive Disease (PD): At least 40% increase in tumor volume compared to the smallest volume obtained since the beginning.
Time Frame Protocol week 6 evaluation
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients with protocol week tumor assessment (N=102)
Arm/Group Title High_Risk_Rhabdomyosarcoma
Hide Arm/Group Description:
Parameningeal (without intracranial extension) and paraspinal tumors receive chemotherapy starting Week 1 and begin radiation therapy at Week 20. Weeks 1-6: vincristine sulfate and irinotecan hydrochloride. Weeks 7-34: vincristine sulfate and irinotecan hydrochloride, Cyclophosphamide with MESNA, Doxorubicin hydrochloride, Etoposide, Ifosfamide with MESNA. Weeks 35-54: vincristine sulfate, Dactinomycin, irinotecan hydrochloride and Cyclophosphamide with MESNA and Filgrastim. Radiation therapy beginning at Week 20. Second look conventional surgery: Surgical resection other than biopsy will be applicable for the majority of patients
Overall Number of Participants Analyzed 102
Measure Type: Number
Unit of Measure: percentage of participants
63
2.Primary Outcome
Title Percentage of Patients Experiencing Adverse Events Due to Concurrent Therapy
Hide Description Adverse events are reported for patients receiving concurrent irinotecan hydrochloride and radiotherapy.
Time Frame From enrollment to up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Percentage of patients experiencing a grade 3/4/5 toxicity in a course.
Arm/Group Title High_Risk_Rhabdomyosarcoma
Hide Arm/Group Description:
Parameningeal (without intracranial extension) and paraspinal tumors receive chemotherapy starting Week 1 and begin radiation therapy at Week 20. Weeks 1-6: vincristine sulfate and irinotecan hydrochloride. Weeks 7-34: vincristine sulfate and irinotecan hydrochloride, Cyclophosphamide with MESNA, Doxorubicin hydrochloride, Etoposide, Ifosfamide with MESNA. Weeks 35-54: vincristine sulfate, Dactinomycin, irinotecan hydrochloride and Cyclophosphamide with MESNA and Filgrastim. Radiation therapy beginning at Week 20. Second look conventional surgery: Surgical resection other than biopsy will be applicable for the majority of patients.
Overall Number of Participants Analyzed 109
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
Course 1
53.3
(43.4 to 63.0)
Course 2
68.4
(58.2 to 77.4)
Course 3
79.3
(69.3 to 87.3)
Course 4
55.7
(43.3 to 67.6)
3.Secondary Outcome
Title Percentage of Patients Event Free at 4 Years Following Study Entry
Hide Description Event-free survival: Time to recurrence, second malignancy, or death as a first event, estimated from a Kaplan Meier curve
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients
Arm/Group Title High_Risk_Rhabdomyosarcoma
Hide Arm/Group Description:
Patients with parameningeal (without intracranial extension) and paraspinal tumors should receive chemotherapy beginning Week 1 and begin radiation therapy at Week 20. Weeks 1-6 vincristine sulfate (VCR) & irinotecan hydrochloride (IRIN), Weeks 7-34 vincristine sulfate (VCR), Cyclophosphamide (CPM) with MESNA, Doxorubicin hydrochloride (DOX), Etoposide (ETOP), Ifosfamide (IFOS) with MESNA. Weeks 35-54 vincristine sulfate (VCR), Dactinomycin (DACT) and Cyclophosphamide (CPM) with MESNA and Filgrastim. Radiation therapy beginning at Week 20. Second look conventional surgery: Surgical resection other than biopsy will be applicable for the majority of patients.
Overall Number of Participants Analyzed 109
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
36
(27 to 46)
Time Frame [Not Specified]
Adverse Event Reporting Description The denominator for adverse events is 108 rather than 109 is because 1 patient did not receive treatment, therefore was excluded from the denominator.
 
Arm/Group Title High_Risk_Rhabdomyosarcoma
Hide Arm/Group Description Parameningeal (without intracranial extension) and paraspinal tumors receive chemotherapy starting Week 1 and begin radiation therapy at Week 20. Weeks 1-6: vincristine sulfate and irinotecan hydrochloride. Weeks 7-34: vincristine sulfate and irinotecan hydrochloride, Cyclophosphamide with MESNA, Doxorubicin hydrochloride, Etoposide, Ifosfamide with MESNA. Weeks 35-54: vincristine sulfate, Dactinomycin, irinotecan hydrochloride and Cyclophosphamide with MESNA and Filgrastim. Radiation therapy beginning at Week 20. Second look conventional surgery: Surgical resection other than biopsy will be applicable for the majority of patients.
All-Cause Mortality
High_Risk_Rhabdomyosarcoma
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
High_Risk_Rhabdomyosarcoma
Affected / at Risk (%)
Total   4/108 (3.70%) 
Infections and infestations   
Anorectal infection  1/108 (0.93%) 
Infections and infestations - Other  1/108 (0.93%) 
Sepsis  1/108 (0.93%) 
Injury, poisoning and procedural complications   
Radiation recall reaction (dermatologic)  1/108 (0.93%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
High_Risk_Rhabdomyosarcoma
Affected / at Risk (%)
Total   95/108 (87.96%) 
Blood and lymphatic system disorders   
Anemia  8/108 (7.41%) 
Blood and lymphatic system disorders - Other  1/108 (0.93%) 
Febrile neutropenia  44/108 (40.74%) 
Cardiac disorders   
Cardiac disorders - other  1/108 (0.93%) 
Pericardial effusion  1/108 (0.93%) 
Supraventricular tachycardia  1/108 (0.93%) 
Gastrointestinal disorders   
Abdominal distension  1/108 (0.93%) 
Abdominal pain  15/108 (13.89%) 
Anal pain  3/108 (2.78%) 
Ascites  1/108 (0.93%) 
Colitis  9/108 (8.33%) 
Constipation  4/108 (3.70%) 
Diarrhea  34/108 (31.48%) 
Dysphagia  3/108 (2.78%) 
Enterocolitis  1/108 (0.93%) 
Esophageal pain  2/108 (1.85%) 
Esophageal stenosis  1/108 (0.93%) 
Esophagitis  4/108 (3.70%) 
Gastritis  1/108 (0.93%) 
Gastrointestinal disorders - Other  2/108 (1.85%) 
Ileus  3/108 (2.78%) 
Lower gastrointestinal hemorrhage  1/108 (0.93%) 
Malabsorption  1/108 (0.93%) 
Mucositis oral  20/108 (18.52%) 
Nausea  21/108 (19.44%) 
Oral pain  4/108 (3.70%) 
Proctitis  1/108 (0.93%) 
Rectal mucositis  2/108 (1.85%) 
Rectal pain  2/108 (1.85%) 
Small intestinal obstruction  2/108 (1.85%) 
Stomach pain  1/108 (0.93%) 
Typhlitis  1/108 (0.93%) 
Vomiting  16/108 (14.81%) 
General disorders   
Edema limbs  1/108 (0.93%) 
Fatigue  7/108 (6.48%) 
Fever  4/108 (3.70%) 
Gait disturbance  2/108 (1.85%) 
General disorders and administration site conditions - Other  1/108 (0.93%) 
Non-cardiac chest pain  2/108 (1.85%) 
Pain  4/108 (3.70%) 
Hepatobiliary disorders   
Hepatic failure  1/108 (0.93%) 
Immune system disorders   
Anaphylaxis  3/108 (2.78%) 
Infections and infestations   
Abdominal infection  2/108 (1.85%) 
Anorectal infection  1/108 (0.93%) 
Bladder infection  3/108 (2.78%) 
Catheter related infection  8/108 (7.41%) 
Enterocolitis infectious  11/108 (10.19%) 
Infections and infestations - Other  51/108 (47.22%) 
Lung infection  1/108 (0.93%) 
Nail infection  1/108 (0.93%) 
Otitis externa  1/108 (0.93%) 
Otitis media  1/108 (0.93%) 
Peripheral nerve infection  1/108 (0.93%) 
Pleural infection  1/108 (0.93%) 
Skin infection  2/108 (1.85%) 
Tooth infection  1/108 (0.93%) 
Upper respiratory infection  4/108 (3.70%) 
Urinary tract infection  4/108 (3.70%) 
Wound infection  1/108 (0.93%) 
Injury, poisoning and procedural complications   
Dermatitis radiation  6/108 (5.56%) 
Radiation recall reaction (dermatologic)  1/108 (0.93%) 
Vascular access complication  1/108 (0.93%) 
Venous injury  1/108 (0.93%) 
Investigations   
Activated partial thromboplastin time prolonged  1/108 (0.93%) 
Alanine aminotransferase increased  12/108 (11.11%) 
Aspartate aminotransferase increased  8/108 (7.41%) 
Blood antidiuretic hormone abnormal  1/108 (0.93%) 
Blood bilirubin increased  4/108 (3.70%) 
Creatinine increased  2/108 (1.85%) 
GGT increased  3/108 (2.78%) 
INR increased  1/108 (0.93%) 
Lipase increased  4/108 (3.70%) 
Lymphocyte count decreased  1/108 (0.93%) 
Neutrophil count decreased  9/108 (8.33%) 
Platelet count decreased  4/108 (3.70%) 
Serum amylase increased  1/108 (0.93%) 
Weight loss  14/108 (12.96%) 
White blood cell decreased  4/108 (3.70%) 
Metabolism and nutrition disorders   
Acidosis  1/108 (0.93%) 
Alkalosis  1/108 (0.93%) 
Anorexia  24/108 (22.22%) 
Dehydration  17/108 (15.74%) 
Hypercalcemia  3/108 (2.78%) 
Hyperglycemia  8/108 (7.41%) 
Hyperkalemia  3/108 (2.78%) 
Hypernatremia  2/108 (1.85%) 
Hyperuricemia  1/108 (0.93%) 
Hypoalbuminemia  5/108 (4.63%) 
Hypocalcemia  5/108 (4.63%) 
Hypoglycemia  1/108 (0.93%) 
Hypokalemia  20/108 (18.52%) 
Hyponatremia  7/108 (6.48%) 
Hypophosphatemia  5/108 (4.63%) 
Musculoskeletal and connective tissue disorders   
Back pain  4/108 (3.70%) 
Bone pain  1/108 (0.93%) 
Buttock pain  1/108 (0.93%) 
Generalized muscle weakness  1/108 (0.93%) 
Muscle weakness lower limb  2/108 (1.85%) 
Muscle weakness upper limb  1/108 (0.93%) 
Musculoskeletal and connective tissue disorder - Other  1/108 (0.93%) 
Myalgia  1/108 (0.93%) 
Neck pain  1/108 (0.93%) 
Pain in extremity  2/108 (1.85%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumor Pain  4/108 (3.70%) 
Nervous system disorders   
Cognitive disturbance  2/108 (1.85%) 
Encephalopathy  1/108 (0.93%) 
Headache  5/108 (4.63%) 
Nervous system disorders - Other  1/108 (0.93%) 
Neuralgia  1/108 (0.93%) 
Peripheral motor neuropathy  8/108 (7.41%) 
Peripheral sensory neuropathy  8/108 (7.41%) 
Seizure  1/108 (0.93%) 
Sinus pain  1/108 (0.93%) 
Syncope  1/108 (0.93%) 
Psychiatric disorders   
Depression  4/108 (3.70%) 
Personality change  1/108 (0.93%) 
Renal and urinary disorders   
Acute kidney injury  1/108 (0.93%) 
Chronic kidney disease  1/108 (0.93%) 
Cystitis noninfective  3/108 (2.78%) 
Hematuria  2/108 (1.85%) 
Proteinuria  1/108 (0.93%) 
Renal and urinary disorders - Other  2/108 (1.85%) 
Urinary tract obstruction  1/108 (0.93%) 
Urinary tract pain  1/108 (0.93%) 
Reproductive system and breast disorders   
Perineal pain  1/108 (0.93%) 
Uterine hemorrhage  1/108 (0.93%) 
Respiratory, thoracic and mediastinal disorders   
Adult respiratory distress syndrome  1/108 (0.93%) 
Cough  2/108 (1.85%) 
Dyspnea  1/108 (0.93%) 
Epistaxis  2/108 (1.85%) 
Hypoxia  5/108 (4.63%) 
Laryngeal edema  1/108 (0.93%) 
Pharyngolaryngeal pain  3/108 (2.78%) 
Pleural effusion  2/108 (1.85%) 
Pneumonitis  4/108 (3.70%) 
Respiratory, thoracic and mediastinal disorders - Other  1/108 (0.93%) 
Skin and subcutaneous tissue disorders   
Purpura  1/108 (0.93%) 
Rash maculo-papular  1/108 (0.93%) 
Vascular disorders   
Hypotension  3/108 (2.78%) 
Thromboembolic event  1/108 (0.93%) 
Vascular disorders - Other  1/108 (0.93%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
EMail: resultsreportingcoordinator@childrensoncologygroup.org
Publications of Results:
Weigel B, Lyden E, Anderson JR, et al.: Early results from Children's Oncology Group (COG) ARST0431: intensive multidrug therapy for patients with metastatic rhabdomyosarcoma (RMS). [Abstract] J Clin Oncol 28 (Suppl 15): A-9503, 2010.
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00354744    
Other Study ID Numbers: ARST0431
CDR0000489215 ( Other Identifier: Clinical Trials.gov )
COG-ARST0431 ( Other Identifier: Children's Oncology Group )
First Submitted: July 19, 2006
First Posted: July 20, 2006
Results First Submitted: September 3, 2013
Results First Posted: January 10, 2014
Last Update Posted: January 29, 2020