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Phase 3 N=481 Randomized Treatment

Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma

Adult Rhabdomyosarcoma · Childhood Alveolar Rhabdomyosarcoma · Childhood Botryoid-Type Embryonal Rhabdomyosarcoma · Childhood Embryonal Rhabdomyosarcoma · Localized Childhood Soft Tissue Sarcoma

Enrolled (actual)
481
Serious AEs
3.4%
Results posted
Jul 2017
Primary outcome: Primary: Event Free Survival (EFS) — 0.6255; 0.5874 Probability

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Cyclophosphamide (Drug); Dactinomycin (Biological); Irinotecan Hydrochloride (Drug); Laboratory Biomarker Analysis (Other); Questionnaire Administration (Other); Radiation Therapy (Radiation); Vincristine Sulfate (Drug)
Age
Pediatric, Adult
Sex
All
Sponsor
Children's Oncology Group
Primary completion
Dec 2014

Outcome Measures

OutcomeResultp-value
PRIMARY
Event Free Survival (EFS)
0.6255; 0.5874
PRIMARY
Response Rate (RR)
0.6667; 0.6726
PRIMARY
Overall Survival (OS)
0.7293; 0.7223
SECONDARY
Event Free Survival (EFS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison
0.6255
SECONDARY
Local Failure
0.1757
SECONDARY
Overall Survival (OS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison
0.7293
SECONDARY
Incidence of Toxicity
0.2072; 0.3673
SECONDARY
Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC
58; 54; 30; 17; 6; 1
SECONDARY
Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 4
0.2857; 0.6364
SECONDARY
Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 15
0.6667; 0.5686
SECONDARY
Incidence of Toxicity Related to VI Treatment in Patients With UGT1A1 Genotype
16; 22; 4; 5; 14; 5 0.99
SECONDARY
Toxicity With CYP2B6 Genotypes
SECONDARY
Toxicity With GSTA1 and CYP2C9 Genotypes
SECONDARY
Event Free Survival (EFS) by PAX Status
0.51; 0.66
SECONDARY
Incidence of Bladder Dysfunction
2; 1

Summary

This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given together with radiation therapy in treating patients with newly diagnosed rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine sulfate, dactinomycin, cyclophosphamide, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective when given together with radiation therapy in treating patients with rhabdomyosarcoma.

Eligibility Criteria

Inclusion Criteria

  • Patients with newly diagnosed embryonal RMS, botryoid or spindle cell variants of embryonal RMS, ectomesenchymoma, or alveolar RMS are eligible for this study
  • Enrollment on COG-D9902 to confirm local histologic diagnosis with central pathology review is required for all patients
  • Patients may be enrolled on ARST0531 and start protocol treatment prior to receipt of central pathology review results
  • Patient must have Intermediate-risk RMS defined as:
  • Embryonal, botryoid, or spindle cell RMS, or ectomesenchymoma: stage 2 or 3 and group III OR
  • Alveolar RMS: stage 1-3 and group I-III
  • Staging ipsilateral retroperitoneal lymph node dissection (SIRLND) is required for all patients >= 10 years of age with paratesticular tumors and for patients 2 cm in dimension, is identified by imaging studies)
  • Regional lymph node sampling or sentinel lymph node procedure is required for histologic evaluation in patients with extremity tumors
  • Clinically or radiographically enlarged nodes should be sampled for histologic evaluation
  • Detection of metastasis by optional FDG PET (not required for study enrollment); FDG PET may detect abnormalities suggestive of metastasis not identified by bone scan, computed tomography (CT), or bone marrow aspiration/biopsy; the prognostic significance of FDG PET-detected abnormalities is not clear; FDG PET-detected abnormalities MUST be confirmed to be metastases by an additional imaging modality (such as magnetic resonance imaging [MRI] or CT) OR pathologic confirmation; unless FDG PET abnormalities are confirmed by another imaging modality or biopsy, FDG PET abnormalities will NOT be considered evidence of metastasis
  • Patients must have a performance status of 0, 1, or 2; the Lansky performance score should be used for patients = 16 years
  • Patients who have received prior chemotherapy (excluding steroids) or radiation therapy, except for patients transferring from ARST0331 (low-risk study), are not eligible
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
  • 1 month to = 16 years: 1.7 mg/dL (males) or 1.4 mg/dL (females)
  • Patients with urinary tract obstruction by tumor must meet the renal function criteria AND must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract
  • Total bilirubin = = 750/uL
  • Platelet count >= 75,000/uL (transfusion independent)
  • No evidence of uncontrolled infection
  • Patients must be able to undergo radiation therapy, if necessary, as specified in the protocol
  • Female patients of childbearing potential must have a negative pregnancy test
  • Female patients who are breast feeding must agree to stop breast feeding
  • Sexually active patients of childbearing potential must be willing to use effective contraception during therapy and for at least 1 month after treatment is completed
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00354835). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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