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

Status: Recruiting
Phase: Phase 2
Diagnosis: Pediatric Solid Tumors
NCT ID: NCT01222715 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 10-413

 

This randomized phase II trial is studying how well giving vinorelbine ditartrate and cyclophosphamide together works in combination with bevacizumab or temsirolimus in treating patients with recurrent or refractory rhabdomyosarcoma. Drugs used in chemotherapy, such as vinorelbine ditartrate 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

 

Conducting Institutions:
Dana-Farber Cancer Institute, Massachusetts General Hospital, Children's Hospital Boston

Overall PI:
Carlos Rodriguez-Galindo, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:
Alison Friedmann, MD, Massachusetts General Hospital

Contacts:
Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

DISEASE CHARACTERISTICS: - Patients must have had a previous histological verification of rhabdomyosarcoma at original diagnosis - Patients with first relapse or progression of rhabdomyosarcoma are eligible - Patients with primary refractory disease are eligible - 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 without measurable or evaluable disease are eligible - Bone marrow disease involvement of tumor is allowed, however, peripheral blood count criteria must still be met - Patients with known CNS disease, 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 (MRI or CT) - Stable dose of anticonvulsants are allowed - Treatment for brain metastases may include whole-brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, 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 PATIENT CHARACTERISTICS: - Patients must have a Karnofsky or Lansky performance status score of ≥ 50%, corresponding to 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 - 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 PRBC transfusions) - Creatinine clearance or radioisotope 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: - For patients aged ≤ 17 years, UPC ratio must be ≤ 1 for patient to be eligible - For 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 < 1000 mg for patient enrollment - Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for the duration of 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 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 PRIOR CONCURRENT THERAPY: - See Disease Characteristics - Patients who previously received vinorelbine, bevacizumab, temsirolimus, or any other direct VEGF/VEGFR- or mTOR- targeting agents are ineligible - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study - For autologous stem cell transplantation (SCT), ≥ 3 months must have elapsed - For allogeneic SCT, ≥ 6 months must have elapsed and no evidence of active graft vs host disease - 3 half-lives (or 6 weeks) must have elapsed since previous monoclonal antibody therapy prior to enrollment on this study - At least 4 weeks must have elapsed between radiotherapy and study entry - Patients who previously received craniospinal irradiation are ineligible - Previously radiated lesions cannot be used to assess response unless those sites are the sites of disease progression - No myelosuppressive chemotherapy within 3 weeks prior to entry onto this study (4 weeks if prior nitrosourea) - 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 - No myeloid growth factor within 1 week prior to entry onto this study - 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 - Patients currently taking anticoagulants or antiplatelet agents with the exception of aspirin (≤ 81 mg/day) are ineligible - Patients may not undergo surgery or radiotherapy during the first 2 courses (6 weeks) of therapy
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