Last updated on August 2019

Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma


Brief description of study

This randomized phase III trial studies how well combination chemotherapy (vincristine sulfate, dactinomycin, cyclophosphamide alternated with vincristine sulfate and irinotecan hydrochloride or vinorelbine) works compared to combination chemotherapy plus temsirolimus in treating patients with rhabdomyosarcoma (cancer that forms in the soft tissues, such as muscle), and has an intermediate chance of coming back after treatment (intermediate risk). Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Combination chemotherapy and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy or combination chemotherapy plus temsirolimus is more effective in treating patients with intermediate-risk rhabdomyosarcoma.

Detailed Study Description

PRIMARY OBJECTIVES:

I. To compare the event-free survival (EFS) of patients with intermediate-risk (IR) rhabdomyosarcoma (RMS) treated with surgery, radiotherapy, and vincristine (vincristine sulfate), dactinomycin, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (irinotecan hydrochloride) (VI) (VAC/VI) with maintenance to that of patients treated with surgery, radiotherapy and VAC/VI plus temsirolimus with maintenance.

SECONDARY OBJECTIVES:

I. To compare the overall survival (OS) of patients with IR RMS treated with surgery, radiotherapy, and VAC alternating with VI with maintenance to that of patients treated with surgery, radiotherapy and VAC/VI plus temsirolimus with maintenance.

EXPLORATORY OBJECTIVES:

I. To compare the outcome of patients based on their forkhead box O1 protein (FOXO1) fusion gene partner, by evaluating paired box (PAX) 3 versus (vs) PAX7 in all patients found to be FOXO1 fusion positive.

II. To compare the outcome of patients based on their [F18]-fluorodeoxy-D-glucose-positron emission tomography (FDG-PET) response at week 9 (positive or negative), as assessed by Deauville criteria (5-point).

III. To estimate the frequency of patients with circulating tumor deoxyribonucleic acid (DNA) (ctDNA) at diagnosis and subsequent time-points.

IV. To compare the outcome of patients (VAC/VI with or without temsirolimus) who have received maintenance therapy on ARST1431 to those who received VAC/VI on ARST0531.

OUTLINE

FEASIBILITY PHASE (THE FEASIBILITY PHASE IS COMPLETE, EFFECTIVE WITH AMENDMENT #1A): (< 21 years old): This is a dose-escalation study of temsirolimus.

Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37, and temsirolimus IV over 30-60 minutes on days 1, 8, and 15. Patients also undergo radiation therapy (RT) beginning week 13 for up to 6.5 weeks. Courses with temsirolimus repeat every 21 days for 12 weeks in the absence of disease progression or unacceptable toxicity.

EFFICACY PHASE: Patients are randomized to Regimen A or B. Patients with disease that is ARMS FOXO1 fusion negative (stage I, group I/II, stage 1, group III [orbit] or stage II, group I/II) are assigned to Regimen C.

REGIMEN A (VAC/VI): Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. Patients also undergo primary site RT beginning at week 13 or metastatic site RT beginning at week 43 for up to 6.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then receive vinorelbine IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide orally (PO) once daily (QD) on days 1-28. Cycles repeats every 28 days for 24 weeks in the absence of disease progression or unacceptable toxicity.

REGIMEN B (VAC/VI TEMSIROLIMUS): Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37 and temsirolimus IV over 30-60 minutes on day 1 of weeks 1-12 and 21-42. Patients also undergo RT as in Regimen A. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then receive vinorelbine IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide PO QD on days 1-28. Cycles repeats every 28 days for 24 weeks in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE (Patients in Regimen A or Regimen B): Patients receive vinorelbine IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 6 cycles.

REGIMEN C (FOXO1 FUSION NEGATIVE): Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-10 and 13-22, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, and 22, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients undergo RT beginning at week 13 for up to 6.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, 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 for up to 10 years.

Clinical Study Identifier: NCT02567435

Find a site near you

Start Over

Bay Area Hospital

Coos Bay, OR United States
  Connect »

Kaiser Permanente-Oakland

Oakland, CA United States
  Connect »

Inova Fairfax Hospital

Falls Church, VA United States
  Connect »

Cleveland Clinic Foundation

Cleveland, OH United States
  Connect »

Sibley Memorial Hospital

Washington, WA United States
  Connect »

PCR Oncology

Arroyo Grande, CA United States
  Connect »

Florida Hospital Orlando

Orlando, FL United States
  Connect »

Childrens Oncology Group

Philadelphia, PA United States
  Connect »

University Hospital

San Antonio, TX United States
  Connect »

Saint Mary's Hospital

West Palm Beach, FL United States
  Connect »

University of Virginia Cancer Center

Charlottesville, VA United States
  Connect »

Ochsner Medical Center Jefferson

New Orleans, LA United States
  Connect »

Katmai Oncology Group

Anchorage, AK United States
  Connect »

Mercy Health Saint Mary's

Grand Rapids, MI United States
  Connect »

Children's Hospital of Alabama

Birmingham, AL United States
  Connect »

Alaska Women's Cancer Care

Anchorage, AK United States
  Connect »

Anchorage Oncology Centre

Anchorage, AK United States
  Connect »

Arkansas Children's Hospital

Little Rock, AR United States
  Connect »

Kaiser Permanente-Anaheim

Anaheim, CA United States
  Connect »

Kaiser Permanente-Bellflower

Bellflower, CA United States
  Connect »

Kaiser Permanente-Fontana

Fontana, CA United States
  Connect »

Children's Hospital Los Angeles

Los Angeles, CA United States
  Connect »

Mattel Children's Hospital UCLA

Los Angeles, CA United States
  Connect »

Yale University

New Haven, CT United States
  Connect »

Nemours Children's Hospital

Orlando, FL United States
  Connect »

Johns Hopkins All Children's Hospital

Saint Petersburg, FL United States
  Connect »

Tampa General Hospital

Tampa, FL United States
  Connect »

Saint John's Hospital

Springfield, IL United States
  Connect »

Blank Children's Hospital

Des Moines, IA United States
  Connect »

Norton Children's Hospital

Louisville, KY United States
  Connect »

Children's Hospital New Orleans

New Orleans, LA United States
  Connect »

Maine Children's Cancer Program

Scarborough, ME United States
  Connect »

C S Mott Children's Hospital

Ann Arbor, MI United States
  Connect »

Bronson Battle Creek

Battle Creek, MI United States
  Connect »

Bronson Methodist Hospital

Kalamazoo, MI United States
  Connect »

West Michigan Cancer Center

Kalamazoo, MI United States
  Connect »

Borgess Medical Center

Kalamazoo, MI United States
  Connect »

Mercy Health Mercy Campus

Muskegon, MI United States
  Connect »

Lakeland Hospital Niles

Niles, MI United States
  Connect »

Huron Medical Center PC

Port Huron, MI United States
  Connect »

Lake Huron Medical Center

Port Huron, MI United States
  Connect »

Marie Yeager Cancer Center

Saint Joseph, MI United States
  Connect »

Munson Medical Center

Traverse City, MI United States
  Connect »

Metro Health Hospital

Wyoming, MI United States
  Connect »

Columbia Regional

Columbia, MO United States
  Connect »

Desert West Surgery

Las Vegas, NV United States
  Connect »

OptumCare Cancer Care at Oakey

Las Vegas, NV United States
  Connect »

21st Century Oncology

Las Vegas, NV United States
  Connect »

Ann M Wierman MD LTD

Las Vegas, NV United States
  Connect »

Saint Peter's University Hospital

New Brunswick, NJ United States
  Connect »

Mount Sinai Hospital

New York, NY United States
  Connect »

Westchester Medical Center

Valhalla, NY United States
  Connect »

East Carolina University

Greenville, NC United States
  Connect »

Geisinger Medical Center

Danville, PA United States
  Connect »

T C Thompson Children's Hospital

Chattanooga, TN United States
  Connect »

Driscoll Children's Hospital

Corpus Christi, TX United States
  Connect »

El Paso Children's Hospital

El Paso, TX United States
  Connect »

University Medical Center

Lubbock, TX United States
  Connect »

Primary Children's Hospital

Salt Lake City, UT United States
  Connect »

Seattle Children's Hospital

Seattle, WA United States
  Connect »

United Hospital Center

Bridgeport, WV United States
  Connect »

WVUH-Berkely Medical Center

Martinsburg, WV United States
  Connect »

Camden Clark Medical Center

Parkersburg, WV United States
  Connect »

John Hunter Children's Hospital

Hunter Regional Mail Centre, Australia
  Connect »

M D Anderson Cancer Center

Houston, TX United States
  Connect »

AdventHealth Orlando

Orlando, FL United States
  Connect »

Palms West Radiation Therapy

Loxahatchee Groves, FL United States
  Connect »