Clinical Trials

Study : NANT 2004-06

¹³¹I-MIBG + High Dose Chemotherapy and Stem Cell Transplant for High Risk Neuroblastoma

Protocol Title: Irinotecan and Vincristine with ¹³¹I-MIBG for Resistant/Relapsed High-Risk Neuroblastoma - A Phase I NANT Study (N2004-06)

Study Chair: Steven Dubois, MD (University of California-San Francisco)

What is this study about:

This study will combine two chemotherapy drugs (irinotecan and vincristine) that have been used together in some patients with neuroblastoma with the experimental chemical agent called Metaiodobenzylguanidine (MIBG). MIBG is taken up by neuroblastoma tumor cells. MIBG can be combined together with radioactive iodine (¹³¹I) in the laboratory to form the radioactive compound ¹³¹I-MIBG. The ¹³¹I-MIBG compound delivers radiation to the neuroblastoma cancer cells and causes them to die. The irinotecan and vincristine will be given at the same time as the ¹³¹I-MIBG. Giving the chemotherapy 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. It is expected that as the dose of ¹³¹I-MIBG is increased, the blood cells will not recover to normal without giving back the patient's own stem cells. This study will be the first study to test giving irinotecan and vincristine together with ¹³¹I-MIBG and will help determine the highest ¹³¹I-MIBG dose that can safely be given together with irinotecan and vincristine to patients with resistant/relapsed neuroblastoma.

Why is this study being done:

This study is being done to try and answer the following questions:

• To find the highest dose of ¹³¹I-MIBG that can be given safely together with irinotecan and vincristine.
• What effects - both good and bad - are seen in patients treated on this study.
• To measure blood levels of irinotecan during treatment
• To find out if specific genes affect side effects caused by irinotecan (like diarrhea).
• To find out if your tumor gets smaller after treatment with ¹³¹I-MIBG together with irinotecan and vincristine.

Criteria that need to be met to participate in this study:

• Patients must be at least one year and no more than 30 years of age when registered on this study.
• Patients must have high risk neuroblastoma and either have tumor left after treatment started at diagnosis or have had the tumor grow back (relapsed) after getting some treatment
• Patients must an MIBG scan done and it must be positive for neuroblastoma.
• Patients must have a PBSC stem cell product available that meets study criteria. If they don't already have stem cells frozen away then they must be able to have a stem cell pheresis done to collect the necessary amount of stem cells for study entry and these stem cells must meet study criteria.
• Patients must have adequate heart, lung, liver, kidney and bone marrow function.

Patients cannot participate in the study if:

• They have had treatment with ¹³¹I-MIBG before.
• They have had a stem cell transplant using another person as the stem cell donor. (You can still be in the study if a previous transplant used your own stem cells)
• They have other medical problems that could get much worse if they had this treatment.
• They are on dialysis for badly working kidneys.
• They are pregnant or breast feeding.
• They have active infections such as hepatitis or fungal infections.
• They have active diarrhea or are allergic to one kind of antibiotic used to treat infection.
• They had total body radiation or radiation to the entire belly or a large amount of radiation to the liver or kidney (some radiation to the liver or kidneys is ok).
• They can't cooperate with the special precautions that are needed during MIBG treatment.

Study procedures:

Click on the graphic above to view a larger version.

MIBG:	M	Day 1
Vincristine:	V	Day 0 and Day 7
Irinotecan:	I	Days 0 through 4 and Days 7 through 11 (days 5 & 6 are rest days where no drug is given)
Cefixime:	C	Days –5 to Day 21
G-CSF	G-CSF	Given any time after day 11 if blood counts are low.
Stem Cells:	SC	Day 13. Stem cell infusion if your blood counts are too low. Your doctor will tell you if you need these.
Evaluation:	Eval	Day 56. Evaluations are done after finishing treatment. Treatment may be repeated at least every 8 weeks as long as your neuroblastoma is responding to treatment, you do not have bad side effects and you have enough stem cells available to get another treatment.

Before chemotherapy starts, you will take the antibiotic cefixime by mouth for five days. Cefixime can be taken in tablet or liquid form. The purpose of the cefixime is to reduce your chance of having bad diarrhea while you are getting irinotecan. Cefixime will be given every day for a total of 27 days. If there is trouble getting Cefixime, another antibiotic called cefpodoxime (Vantin-R) can be used instead.

After 5 days of cefixime you will start taking irinotecan, vincristine and ¹³¹I-MIBG. Irinotecan is given daily for 5 days in a row then 2 days of rest followed by another 5 days for a total of 10 doses over 2 weeks. Irinotecan is given by IV. Vincristine is given on the first day irinotecan is given each week for a total of 2 doses. Vincristine is also given by IV.

You will be treated once with ¹³¹I-MIBG during the first week on day 1.

MIBG treatment is done at a hospital that is set up to take care of patients that are treated with radioactive substances. For this study, these hospitals are located in San Francisco, CA, Philadelphia, PA, Ann Arbor, MI and Cincinnati, OH. Patients who get MIBG are considered to be "hot' or radioactive and special precautions are taken to care for you during this time until the radiation has gone down to a level where these precautions are no longer needed. You are in your own room and the time family members can be in the room with you is limited at first but will increase every day as the radiation level goes down. MIBG is given by IV over 2 hours.

If you would like to download or print the sample consent form for this clinical trial, please click here : N04-06 consent form

If you would like to download this page in Microsoft Word format, please click here : N2004-06

[ If you are interested in getting more information about this clinical trial, please click here to send us an email. ]