Study : NANT 2007-03
Vorinostat and MIBG in Recurrent or Resistant Neuroblastoma Patients
Protocol Title: Vorinostat With 131I-MIBG Therapy for Resistant/Relapsed Neuroblastoma: A Phase 1 Study (IND# 105, 744)
Study Chair: Steven DuBois, MD. (University of California, San Francisco School of Medicine)
What is this study about:
This study will combine an oral drug called vorinostat with an intravenous agent called metaiodobenzylguanidine (MIBG) that can be used to deliver radiation to neuroblastoma tumors.
Vorinostat is a drug that is FDA-approved to treat a certain type of cancer mainly seen in adults. Vorinostat affects the way the DNA that carries our genes is folded in cells. In the laboratory, vorinostat causes neuroblastoma cells to stop growing. This effect is even greater when vorinostat is combined with radiation.
MIBG is taken up by neuroblastoma tumor cells. MIBG can be combined together with radioactive iodine (131I) to form the radioactive compound 131I-MIBG. The 131I-MIBG compound delivers radiation to the neuroblastoma cancer cells and causes them to die.
Giving vorinostat together with the 131I-MIBG may help the 131I-MIBG to kill more neuroblastoma cells. 131I-MIBG lowers the number of blood forming cells (called stem cells) in the bone marrow when it is given at higher doses. Since the combination of vorinostat and 131I-MIBG is expected to increase this effect, all patients will get back their own stem cells to help the bone marrow recover from this therapy.
This study will be the first study to test giving vorinostat together with 131I-MIBG and will help determine the highest doses of vorinostat and 131I-MIBG that can safely be given together to patients with resistant/relapsed neuroblastoma.
Why is this study being done:
Criteria that need to be met to participate in this study
Patients cannot participate in the study if:
Patients will be assigned a certain vorinostat dose and a certain 131I-MIBG dose. This study will test up to 4 vorinostat doses and up to four 131I-MIBG doses in groups of 3-6 patients. The starting vorinostat dose for the first group of patients is about 20% lower than what is currently being given to patients receiving vorinostat alone without bad side effects. The dose of 131I-MIBG will then be increased in the second group of patients. If this is tolerated without serious side effects, then the vorinostat and 131I-MIBG doses will be increased ("dose escalation") in groups of 3-6 patients until serious side effects are seen. At that point, investigators will have found the highest dose of vorinostat and 131I-MIBG that can be given together without bad side effects.
An additional six patients will be treated at the highest dose of vorinostat and 131I-MIBG to learn more about the side effects and the response of the tumor with those doses.
Patients will receive vorinostat by mouth once a day on Days 1-14, and will be started prior to a hospital admission. Vorinostat will be given as a liquid in all patients. 131I-MIBG will be given in the hospital on Day 3. Patients will get their stem cells back on Day 17 and receive GCSF (Neupogen or filgrastim) until their white blood cells recover.
Patients will be evaluated after finishing this treatment around 2 months after starting.
Patients will receive this combination of vorinostat and 131I-MIBG up to two times as part of this study.
This diagram outlines the treatment regime for one course of therapy on this study: