Work | Tumor Initiating Cells
Rapamycin + Vinblastine Phase I Study
A Phase I Study of Vinblastine in Combination with Rapamycin in Pediatric Patients with Recurrent or Refractory Solid Tumors Including CNS Tumors
This Phase 1 study is a direct result of the Neuroblastoma Drug Discovery Program (NDDP), an innovative program to screen existing and potential new therapies in the pre-clinical stage for neuroblastoma. In 2008 two agents with anti-cancer properties for neuroblastoma were identified through the NDDP. Clinical results showed that the agents, Vinblastine and Rapamycin, killed isolated patient neuroblastoma stem (tumor-initating) cells in the laboratory and controlled tumor growth in animal models.
Both Vinblastine and Rapamycin, existing and available agents for cancer and transplants respectively, have been found to be safe and effective in children for unrelated indications but have never been used in combination for neuroblastoma and other solid pediatric tumors It is thought that these two agents may act by blocking new blood vessel formation and as a result directly kill neuroblastoma cells by interfering with the mechanism of new tumor blood vessel formation (angiogenesis). Rapamycin also inhibits an important pathway implicated in the progression of neuroblastoma, mTor. When combined into therapy, it is thought that it provides a powerful multi-fronted attack on these complex cancers.
This phase 1 clinical trial will establish the tolerable dose and schedule of administration of these two agents and will also be used to confirm the postulated mechanism of action and preliminary evidence of efficacy. The novelty of this trial is that tumor cells extracted from the bone marrow of neuroblastoma patients will also be grown separately in culture and injected into mice for testing the efficacy of Rapamycin combined with Vinblastine. This experimental "from patients back to mice" will allow the comparison of the results obtained in patient with the one obtained in mice in the laboratory.
This trial will enroll children throughout North America with sites at Hospital for Sick Kids Toronto, University of Vermont, MD Anderson Cancer Center, Children’s Hospital of San Diego, and St. Louis University. Importantly, this is the first study emerging from the NDDP, a pre-clinical program funded by SKC that has progressed to a Phase 1 clinical trial.
This Phase 1 study has been largely funded by generous individuals. We are grateful for their support.
Puzzle Masters ($10,000 sponsors)
- John and Stacey Giordano
- John and Catherine London
Solvers ($5,000 sponsors)
- Rob Adler
- Chris Casey
- Jonathan Koerner
- Steve Logan
- Mark and Laura Jean Mallon
- Richard Potapchuk
- Adam Radosti
- Ari and Susan Spar
- Mark Vanacore
- Steven and Liz Weinstein
Challengers ($1,000 sponsors)
- Joe Aurilio
- Gerard Betts
- Eric Bernstein
- David Blaustein
- Richard Blond
- Mark Boyer
- Richard Brusselback
- Paul Cipriano
- Tim Cooney
- William Elbery
- Brad Frey
- Joseph Genovese
- David Hibbs
- Brett Jacknow
- James Jordan
- David Kaplan
- John Kennedy
- James Kenney
- Barbara London
- James London
- Todd Lowen
- Micha Magid
- Tim Mann
- Robert Meringolo
- Sean Monaghan
- Wayne Robinson
- Brett Spector
- Mike Solomon
- Chris Suozzi
- Jason Varnish
Relevant Articles and Links
Therapeutic Development Project Links
- Nifurtimox Phase I Clinical Trial
- Nifurtimox Phase II Clinical Trial
- Neuroblastoma Drug Discovery Program
- Rapamycin + Vinblastine Phase I Study
- Patient-specific Therapeutic Development for Neuroblastoma
- Oncolytic Virus Program
- Development Program for Neuroblastoma-specific Oncolytic Virus
- Natural Killer Cell Transplant Pilot Study
- Phase I Clinical Trial of HSV Oncolytic Virus