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

Completed · Phase 2

Conditions studied: Adult Rhabdomyosarcoma, Childhood Alveolar Rhabdomyosarcoma, Childhood Pleomorphic Rhabdomyosarcoma, Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features, Previously Treated Childhood Rhabdomyosarcoma, Recurrent Adult Soft Tissue Sarcoma, Recurrent Childhood Rhabdomyosarcoma

In brief

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.

Key facts

Study ID

NCT01222715

Run by

National Cancer Institute (NCI)

People needed

87

Starts

2010-10-01

Expected to finish

2015-06-01

Last updated by the study team

2017-05-05

Who can join

Age: any, up to 29. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• 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)

You may not qualify if…

• 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
• 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)

Where it is running

• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States
• Phoenix Childrens Hospital — Phoenix, Arizona, United States
• Arkansas Children's Hospital — Little Rock, Arkansas, United States
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States
• Southern California Permanente Medical Group — Downey, California, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Miller Children's and Women's Hospital Long Beach — Long Beach, California, United States
• Children's Hospital Los Angeles — Los Angeles, California, United States
• Cedars-Sinai Medical Center — Los Angeles, California, United States
• Children's Hospital Central California — Madera, California, United States
• Children's Hospital and Research Center at Oakland — Oakland, California, United States
• Children's Hospital of Orange County — Orange, California, United States
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• Rady Children's Hospital - San Diego — San Diego, California, United States
• UCSF Medical Center-Parnassus — San Francisco, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center — Denver, Colorado, United States
• Connecticut Children's Medical Center — Hartford, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• Alfred I duPont Hospital for Children — Wilmington, Delaware, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Lee Memorial Health System — Fort Myers, Florida, United States
• Children's Hospital of Alabama — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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