Title (COG ARST0921) A Randomized Phase II Trial of Bevacizumab (IND #7921, Avastin) and Temsirolimus (IND #61010, Torisel) in Combination with Intravenous Vinorelbine and Cyclophosphamide in Patients with Recurrent/Refractory Rhabdomyosarcoma
Principal Investigator Martin Brecher, MD
Study Number 188210
Summary The primary goals of this randomized Phase II study are to determine the feasibility of administering bevacizumab or temsirolimus with chemotherapy regimen of intravenous vinorelbine and cyclophosphamide (VC), and to compare the event-free survival (EFS) between patients with recurrent/refractory RMS treated with VC + Bevacizumab and those treated with VC + temsirolimus. The study results will provide background data to support the feasibility of the addition of bevacizumab or temsirolimus to VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy in either intermediated - or high-risk RMS patients. In addition, comparison of the EFS between the 2 arms will allow a rational selection of bevacizumab versus temsirolimus as a biologic agent to be tested in patients with newly diagnosed RMS.
- Patients must be < 30 years of age at the time of study enrollment.
- 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 < or equal to 16 years of age.
- Patients must have a life expectancy of > or equal to 8 weeks.
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study (see section 3.2.5). Patients must also have recovered from any surgical procedure before enrolling on this study.
- All patients must have adequate bone marrow function, adequate renal function, adequate liver function, and adequate cardiac function (see section 3.2.6 for definitions).
- Patients with botryoid histology, any stage or group are ineligible. Patients with embryonal histology, Stage 1 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 with known CNS disease (excluding intracranial/intraspinal extension secondary to local progression of a paramieningeal or paraspinal primary), except for those with treated brain metastasis, are ineligible.
- Patients who previously received vinorelbine, bevacizumab, temsirolimus or any other direct VEGF/VEGFR- or mTOR- targeting agents are ineligible.
- Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. 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 pre-existing conditions such as a documented chronic non-healing wound, ulcer, or significant trauma injury within 28 days prior to study entry; patients with evidence of intratumoral hemorrhage, gastrointestinal bleeding, or on anticoagulation for thrombosis or history of thrombosis; with the exception of aspirin; patients with history of central venous catheter (CVC) - associated thrombosis requiring systemic anticoagulation; patients with clinically significant cardiovascular disease are ineligible for this study.