AzTrials
AzTrials

Adult RhabdomyosarcomaPhase 2NCT01222715

Vinorelbine Tartrate and Cyclophosphamide in Combination With Bevacizumab or Temsirolimus in Treating Patients With Recurrent or Refractory Rhabdomyosarcoma

A Phase 2 study testing Bevacizumab, Cyclophosphamide and Laboratory Biomarker Analysis in people with Adult Rhabdomyosarcoma and Childhood Alveolar Rhabdomyosarcoma, run by National Cancer Institute (NCI) at 184 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This randomized phase II trial studies how well vinorelbine tartrate and cyclophosphamide work in combination with bevacizumab or temsirolimus in treating patients with recurrent or refractory rhabdomyosarcoma. Read more about this study

Who is it for?
Ages Up to 29 years
What is being tested?
Bevacizumab, Cyclophosphamide and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
87 participants
Where
184 sitesin 4 countries
Study dates
Oct 2010to Jun 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 29 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Diagnosis
  • Patients with first relapse or progression of rhabdomyosarcoma are eligible
  • Patients with primary refractory disease are eligible
  • Primary refractory disease is defined as first progression after receiving at least one course of cyclophosphamide or ifosfamide containing chemotherapy without prior demonstration of a radiographic response to chemotherapy (progression on irinotecan-containing chemotherapy without cyclophosphamide or ifosfamide containing chemotherapy will not be considered a first progression)
  • Note: Patients without measurable or evaluable disease are eligible
  • Patients must have had a previous histological verification of rhabdomyosarcoma at original diagnosis
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  • Patients must have a Karnofsky or Lansky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Patients must have a life expectancy of >= 8 weeks
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
  • Myelosuppressive chemotherapy: Must not have received within 3 weeks prior to entry onto this study (4 weeks if prior nitrosourea)
  • Biologic (anti-neoplastic agent):
  • Patients may have received prior therapy with oral tyrosine kinase inhibitors or other similar agents; at least 7 days must have elapsed since the completion of therapy with a biologic agent and all toxicities must have resolved to < grade 2 prior to enrollment
  • 3 half-lives (or 6 weeks) must have elapsed since previous monoclonal antibody therapy prior to enrollment on this study
  • Myeloid growth factor: Must not have received within 1 week prior to entry onto this study
  • Radiation therapy (RT): At least 4 weeks must have elapsed between RT and study entry; previously radiated lesions cannot be used to assess response unless those sites are the sites of disease progression
  • Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed; for allogeneic SCT, >= 6 months must have elapsed and no evidence of active graft vs. host disease
  • Patients must have recovered from any surgical procedure before enrolling on this study
  • Minor surgical procedures (e.g., biopsies involving core or fine-needle aspiration procedures, infusaport or Broviac line placement, paracentesis, or thoracocentesis) need to have fully healed and occurred > 7 days prior to enrollment
  • Patients who have had a major surgical procedure (such as laparotomy, thoracotomy, open biopsy, or resection of tumor) can only be enrolled on study > 28 days from such procedure
  • Peripheral absolute neutrophil count (ANC) >= 750/μL
  • Platelet count >= 75,000/μL (transfusion independent, defined as without transfusion for >= 1 week prior to enrollment)
  • Hemoglobin >= 8.0 g/dL (may receive packed red blood cells [PRBC] transfusions)
  • Bone marrow disease involvement of tumor is allowed, however, peripheral blood count criteria must still be met
  • 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:
  • =< 0.4 mg/dL (for patients aged 1 month to < 6 months)
  • =< 0.5 mg/dL (for patients aged 6 months to < 1 year)
  • =< 0.6 mg/dL (for patients aged 1 to < 2 years)
  • =< 0.8 mg/dL (for patients aged 2 to < 6 years)
  • =< 1 mg/dL (for patients aged 6 to < 10 years)
  • =< 1.2 mg/dL (for patients aged 10 to < 13 years)
  • =< 1.4 mg/dL (for female patients aged >= 13 years)
  • =< 1.5 mg/dL (for male patients aged 13 to < 16 years)
  • =< 1.7 mg/dL (for male patients aged >= 16 years)
  • Urine protein level:
  • Patients aged =< 17 years: Urine protein to creatinine (UPC) ratio should be calculated; UPC ratio must be =< 1 for patient to be eligible
  • Patients aged > 17 years: Urine protein should be screened by urine analysis; if protein is 2+ or higher, 24-hour urine protein must be obtained and the level must be < 1,000 mg for patient enrollment
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 50% by radionuclide angiogram

Who cannot join

  • Patients with botryoid histology, any stage or group, are ineligible
  • Patients with embryonal histology, stage I or clinical group 1 at initial disease presentation, who present with local or regional recurrence, are ineligible
  • Patients who previously received craniospinal irradiation are ineligible
  • Patients who previously received vinorelbine, bevacizumab, temsirolimus, or any other direct vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR-) or mammalian target of rapamycin (mTOR-) targeting agents are ineligible
  • Patients with known central nervous system (CNS) disease (excluding intracranial/intraspinal extension secondary to local progression of a parameningeal or paraspinal primary), except for those with treated brain metastasis, are ineligible
  • Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]); stable dose of anticonvulsants are allowed; treatment for brain metastases may include whole-brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or equivalent), or a combination as deemed appropriate by the treating physician
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  • Patients with CNS metastases treated within 3 months prior to enrollment by neurosurgical resection or brain biopsy are ineligible
  • Patients who receive radiation or chemotherapy (inclusive of palliative intent) for first disease progression or relapse of rhabdomyosarcoma prior to enrollment are ineligible
  • Female patients who are pregnant are ineligible
  • Lactating females are not eligible unless they have agreed to discontinue breastfeeding
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
  • Patients with a documented chronic non-healing wound, ulcer, or significant trauma injury (those with bone fractures, including pathological fractures, or requiring surgical intervention) within 28 days prior to beginning therapy are ineligible
  • Patients with evidence of intratumoral hemorrhage, gastrointestinal bleeding, or on anticoagulation for thrombosis or history of thrombosis are ineligible
  • Patients with uncontrolled hypertension are ineligible; uncontrolled hypertension is defined as follows:
  • Patients aged =< 17 years: greater than 95th percentile systolic and diastolic blood pressure based on age and height that is not controlled by one antihypertensive medication
  • Patients aged > 17 years: systolic blood pressure >= 160 mm Hg and/or diastolic blood pressure >= 90 mm Hg that is not controlled by one antihypertensive medication
  • Patients currently taking anticoagulants or antiplatelet agents with the exception of aspirin (=< 81 mg/day) are ineligible
  • Patients with history of central venous catheter (CVC)-associated thrombosis requiring systemic anticoagulation are ineligible; Note: Patients with history of sluggish flow from CVC or CVC-associated thrombosis treated with tissue plasminogen activator (TPA) only are not excluded
  • Patients with clinically significant cardiovascular disease are excluded:
  • History of cerebrovascular accident (CVA) within the prior 6 months
  • Myocardial infarction or unstable angina within the prior 6 months
  • New York Heart Association grade 2 or greater congestive heart failure
  • Serious and inadequately controlled cardiac arrhythmia
  • Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)
  • Clinically significant peripheral vascular disease
  • Patients diagnosed with rhabdomyosarcoma as a second malignant neoplasm are not eligible
  • Patients with history of any second malignant neoplasm who have received chemotherapy or radiation for the treatment of that malignancy are not eligible

Trial locations and contacts

184 sites in 4 countries.

184 sites in 4 countries

United States163 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical Center

    Albany, New York, 12208

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87102

  • Texas Tech University Health Science Center-Amarillo

    Amarillo, Texas, 79106

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Mission Hospital-Memorial Campus

    Asheville, North Carolina, 28801

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia, 30322

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Saint Luke's Mountain States Tumor Institute

    Boise, Idaho, 83712

  • Floating Hospital for Children at Tufts Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber/Harvard Cancer Center

    Boston, Massachusetts, 02115

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of Vermont College of Medicine

    Burlington, Vermont, 05405

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • West Virginia University Charleston

    Charleston, West Virginia, 25304

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • T C Thompson Children's Hospital

    Chattanooga, Tennessee, 37403

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • University of Missouri - Ellis Fischel

    Columbia, Missouri, 65212

  • Palmetto Health Richland

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

  • Blank Children's Hospital

    Des Moines, Iowa, 50309

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Saint John Hospital and Medical Center

    Detroit, Michigan, 48236

  • Southern California Permanente Medical Group

    Downey, California, 90242

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Michigan State University Clinical Center

    East Lansing, Michigan, 48824-7016

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Sanford Medical Center-Fargo

    Fargo, North Dakota, 58122

  • Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Brooke Army Medical Center

    Fort Sam Houston, Texas, 78234

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503

  • Saint Vincent Hospital

    Green Bay, Wisconsin, 54301

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Greenville Cancer Treatment Center

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Penn State Hershey Children's Hospital

    Hershey, Pennsylvania, 17033

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Saint Vincent Hospital and Health Care Center

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • Kalamazoo Center for Medical Studies

    Kalamazoo, Michigan, 49008

  • The Childrens Mercy Hospital

    Kansas City, Missouri, 64108

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • Nevada Cancer Research Foundation CCOP

    Las Vegas, Nevada, 89106

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Saint Barnabas Medical Center

    Livingston, New Jersey, 07039

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Kosair Children's Hospital

    Louisville, Kentucky, 40202

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • Children's Hospital Central California

    Madera, California, 93636-8762

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • Winthrop University Hospital

    Mineola, New York, 11501

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Saint Peter's University Hospital

    New Brunswick, New Jersey, 08901

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Yale University

    New Haven, Connecticut, 06520

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

  • Tulane University Health Sciences Center

    New Orleans, Louisiana, 70112

  • Children's Hospital New Orleans

    New Orleans, Louisiana, 70118

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • Columbia University/Herbert Irving Cancer Center

    New York, New York, 10032

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Childrens Hospital-King's Daughters

    Norfolk, Virginia, 23507

  • Children's Hospital and Research Center at Oakland

    Oakland, California, 94609-1809

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Florida Hospital Orlando

    Orlando, Florida, 32803

  • Nemours Children's Clinic - Orlando

    Orlando, Florida, 32806

  • UF Cancer Center at Orlando Health

    Orlando, Florida, 32806

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • Saint Jude Midwest Affiliate

    Peoria, Illinois, 61637

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Legacy Emanuel Hospital and Health Center

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • Memorial University Medical Center

    Savannah, Georgia, 31404

  • Maine Children's Cancer Program

    Scarborough, Maine, 04074

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Cardinal Glennon Children's Medical Center

    St Louis, Missouri, 63104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Overlook Hospital

    Summit, New Jersey, 07902

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

  • Scott and White Memorial Hospital

    Temple, Texas, 76508

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467-2490

  • The Toledo Hospital/Toledo Children's Hospital

    Toledo, Ohio, 43606

  • Mercy Children's Hospital

    Toledo, Ohio, 43608

  • Natalie Warren Bryant Cancer Center at Saint Francis

    Tulsa, Oklahoma, 74136

  • New York Medical College

    Valhalla, New York, 10595

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Saint Mary's Hospital

    West Palm Beach, Florida, 33407

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada16 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Chedoke Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8S 4L8

  • Cancer Centre of Southeastern Ontario at Kingston General Hospital

    Kingston, Ontario, K7L 5P9

  • Children's Hospital

    London, Ontario, N6A 5W9

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec, H3H 1P3

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Centre Hospitalier Universitaire de Quebec

    Québec, Quebec, G1V 4G2

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Janeway Child Health Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia3 sites

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6008

  • Sydney Children's Hospital

    Randwick, New South Wales, 2031

  • The Children's Hospital at Westmead

    Westmead, New South Wales, 2145

Other trials in Australia

New Zealand2 sites

  • Christchurch Hospital

    Christchurch, 8011

  • Starship Children's Hospital

    Grafton, Auckland, 1145

Other trials in New Zealand

About this study

Official title: A Randomized Phase II Trial of Bevacizumab (Avastin) and Temsirolimus (Torisel) in Combination With Intravenous Vinorelbine and Cyclophosphamide in Patients With Recurrent/Refractory Rhabdomyosarcoma

This randomized phase II trial studies how well vinorelbine tartrate and cyclophosphamide work in combination with bevacizumab or temsirolimus in treating patients with recurrent or refractory rhabdomyosarcoma. Drugs used in chemotherapy, such as vinorelbine tartrate and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of rhabdomyosarcoma by blocking blood flow to the tumor. 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 is more effective when given together with bevacizumab or temsirolimus in treating rhabdomyosarcoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the feasibility of administering bevacizumab in combination with intravenous vinorelbine (vinorelbine tartrate) and cyclophosphamide (VC) in patients with recurrent rhabdomyosarcoma (RMS).

II. To determine the feasibility of administering temsirolimus in combination with VC in patients with recurrent RMS.

III. To estimate the event-free survival (EFS) of patients with recurrent/refractory RMS treated with bevacizumab and VC and compare with the EFS of those treated with temsirolimus and VC.

SECONDARY OBJECTIVES:

  1. To estimate the initial (2 cycle) response rate of patients with recurrent/refractory RMS treated with bevacizumab and VC and compare with the response rate of those treated with temsirolimus and VC, and to also compare the best response rate on each regimen of protocol therapy.

II. To evaluate surrogate biological markers in patients with recurrent RMS and to estimate differences in these markers following treatment with bevacizumab and temsirolimus.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive vinorelbine tartrate intravenously (IV) over 6-10 minutes on days 1 and 8 and cyclophosphamide IV over 30-60 minutes on day 1. Patients also receive bevacizumab IV over 30-90 minutes on day 1.

ARM II: Patients receive vinorelbine tartrate and cyclophosphamide as in arm I. Patients also receive temsirolimus IV over 30-60 minutes on days 1, 8, and 15.

In both arms, treatment repeats every 21 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for 5 years.

Being tested
Bevacizumab, Cyclophosphamide, Laboratory Biomarker Analysis, Temsirolimus, Vinorelbine Tartrate
Medical subject headings
Rhabdomyosarcoma, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • TemsirolimusDrug

    Also called CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog

    Given IV

  • Vinorelbine TartrateDrug

    Also called Biovelbin, Eunades, KW-2307, Navelbine

    Given IV

Study groups in NCT01222715
Study groupRoleWhat they receive
Arm I (vinorelbine tartrate, cyclophosphamide, bevacizumab)ExperimentalPatients receive vinorelbine tartrate IV over 6-10 minutes on days 1 and 8 and cyclophosphamide IV over 30-60 minutes on day 1. Patients also receive bevacizumab IV over 30-90 minutes on day 1.
Receives: Biological: Bevacizumab; Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Drug: Vinorelbine Tartrate
Arm II (vinorelbine tartrate, cyclophosphamide, temsirolimus)ExperimentalPatients receive vinorelbine tartrate and cyclophosphamide as in arm I. Patients also receive temsirolimus IV over 30-60 minutes on days 1, 8, and 15.
Receives: Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Drug: Temsirolimus; Drug: Vinorelbine Tartrate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event Free Survival Probability

    Probability of no relapse, secondary malignancy, or death after 1 year in the study.

    Measured: 1 year

  2. Rate of Dose-Limiting Toxicities

    The following events will be considered dose-limiting toxicities (DLTs): Toxicity causing delays > 14 days in delivery of a 21-day cycle of therapy; Grade ≥ 3 mucositis > 3 days duration; Grade ≥ 3 thromboembolic events; Grade ≥ 3 bleeding events; Grade ≥ 3 pulmonary events; Grade ≥ 3 hypertension; Grade 3 hyperglycemia (uncontrolled); Grade ≥ 4 hyperglycemia; Grade ≥ 4 hyperlipidemia (including cholesterol and triglycerides) that does not return to ≤ Grade 2 levels with appropriate medical management within 35 days; Grade ≥ 2 perforation including fistula or leak (gastrointestinal or any other organ); Grade ≥ 3 proteinuria; Grade ≥ 3 cardiac toxicity; Grade ≥ 3 intra-abdominal abscess/infection; Grade ≥ 3 wound complication (wound infection or dehiscence); Grade ≥ 1 Reversible Posterior Leukoencephalopathy Syndrome (RPLS); Grade ≥ 1 Microangiopathy, or Hemolytic-uremic syndrome (HUS) or Thrombotic thrombocytopenic Purpura (TTP).

    Measured: From the date of randomization until a maximum of 12 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities.

Secondary outcomes (1)

  1. Response Rate (CR + PR)

    Complete or partial anatomical response rate. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

    Measured: From the date of randomization until a maximum of 2 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionJun 2015
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01222715
Sponsor's protocol ID
NCI-2011-02607
Other IDs
NCI-2011-02607, COG-ARST0921, CDR0000687113, ARST0921, ARST0921, ARST0921, U10CA098543
Status last verified
Mar 2017
First submitted
15 Oct 2010
Last updated
5 May 2017

Publications

  • Mascarenhas L, Chi YY, Hingorani P, Anderson JR, Lyden ER, Rodeberg DA, Indelicato DJ, Kao SC, Dasgupta R, Spunt SL, Meyer WH, Hawkins DS. Randomized Phase II Trial of Bevacizumab or Temsirolimus in Combination With Chemotherapy for First Relapse Rhabdomyosarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2019 Nov 1;37(31):2866-2874. doi: 10.1200/JCO.19.00576. Epub 2019 Sep 12.

    PubMed 31513481

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Cyclophosphamide and Laboratory Biomarker Analysis in people with Adult Rhabdomyosarcoma and Childhood Alveolar Rhabdomyosarcoma, run by National Cancer Institute (NCI) at 184 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 184 sites in United States, Canada, Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event Free Survival Probability (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01222715, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2017.

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