A Randomized Phase 3 Trial of Vinorelbine, Dactinomycin, and Cyclophosphamide (VINO-AC) Plus Maintenance Chemotherapy With Vinorelbine and Oral Cyclophosphamide (VINO-CPO) vs Vincristine, Dactinomycin and Cyclophosphamide (VAC) Plus VINO-CPO Maintenance in Patients With High Risk Rhabdomyosarcoma (HR-RMS)
This phase III trial compares the effect of vinorelbine with vincristine, dactinomycin, and cyclophosphamide (VAC) followed by vinorelbine and cyclophosphamide versus VAC followed by vinorelbine and cyclophosphamide for the treatment of high risk rhabdomyosarcoma. Chemotherapy drugs, such as vinorelbine, vincristine, dactinomycin, and cyclophosphamide, work in different ways to stop the growth of tumour cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vinorelbine and VAC may kill more tumour cells. Adding maintenance therapy (vinorelbine and cyclophosphamide) after VAC therapy, with or without vinorelbine, may help get rid of the cancer and/or lower the chance that the cancer comes back.
PRIMARY OBJECTIVE:
- To compare event-free
survival (EFS) of patients with high-risk rhabdomyosarcoma (HR-RMS)
treated with vinorelbine, dactinomycin and cyclophosphamide (VINO AC)
followed by 24 weeks of vinorelbine and oral cyclophosphamide (VINO-CPO)
maintenance therapy to that of patients treated with vincristine,
dactinomycin and cyclophosphamide (VAC) followed by 24 weeks of VINO-CPO
maintenance therapy.
SECONDARY OBJECTIVES:
- To assess the safety and feasibility of administering VINO-AC in newly diagnosed patients with HR-RMS.
- To describe the toxicity experience of patients with HR-RMS treated with VINO-AC compared to VAC.
- To compare overall
survival (OS) of patients with HR-RMS treated with VINO AC followed by
24 weeks of VINO-CPO maintenance therapy to that of patients treated
with VAC followed by 24 weeks of VINO-CPO maintenance therapy.
- To compare objective
radiologic response rates at week 12 between patients with HR-RMS
treated with VINO-AC to those treated with VAC.
- To determine whether
the addition of 24 weeks of VINO-CPO maintenance therapy improves EFS in
patients with HR-RMS when compared to historical controls.
EXPLORATORY OBJECTIVE:
- To collect serial
blood samples and tumour tissue for banking at baseline, during
treatment, at the end of therapy, and at the time of progression for
future tumour and liquid biopsy studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive
vincristine sulfate intravenously (IV) on days 1, 8 and 15 of cycles
1-4, 7, 8, 11, and 12, and day 1 of cycles 6, 9, 10, 13, and 14.
Patients also receive dactinomycin IV over 1-15 minutes on day 1 of
cycles 1-5 and 8-14, and cyclophosphamide IV over 60 minutes on day 1 of
each cycle. Treatment repeats every 21 days for up to 14 cycles in the
absence of disease progression or unacceptable toxicity. Patients also
undergo radiation therapy on weeks 13 and 40.
ARM B: Patients receive
vinorelbine tartrate IV over 6-10 minutes on days 1 and 8, vincristine
sulfate IV on day 15, dactinomycin IV over 1-15 minutes on day 1 of
cycles 1-5 and 8-14, and cyclophosphamide IV over 60 minutes on day 1.
Treatment repeats every 21 days for up to 14 cycles in the absence of
disease progression or unacceptable toxicity. Patients also undergo
radiation therapy on weeks 13 and 40.
MAINTENANCE: All
patients receive vinorelbine tartrate IV over 6-10 minutes on days 1, 8,
and 15, and cyclophosphamide orally (PO) on days 1-28. Treatment
repeats every 28 days for up to 6 cycles in the absence of disease
progression or unacceptable toxicity.
After completion of
study treatment, patients are followed up every 3 months for year 1,
every 4 months for years 2-3, and every 6 months for year 4.
