Trial Outcomes & Findings for High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed Neuroblastoma (NCT NCT01313936)

NCT ID: NCT01313936

Last Updated: 2019-04-29

Results Overview

To determine whether doses of 15 mCi/kg and 18 mCi/kg of 131I-MIBG are tolerable when given with irinotecan/vincristine on a 5-day schedule to children and young adults with high-risk refractory/relapsed neuroblastoma.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 32 participants
• Primary outcome timeframe: 6 weeks
• Results posted on: 2019-04-29

Participant Flow

Participant milestones

Measure	15 mCi/kg of 131I-MIBG The first cohort for safety will be 3-6 patients treated with vincristine and irinotecan and 15 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	18 mCi/kg of 131I-MIBG The second cohort will be 3-6 patients at the same doses of vincristine and irinotecan and 18 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.
Overall Study STARTED	6	26
Overall Study COMPLETED	6	26
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed Neuroblastoma

Baseline characteristics by cohort

Measure	15 mCi/kg of 131I-MIBG n=6 Participants The first cohort for safety will be 3-6 patients treated with vincristine and irinotecan and 15 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	18 mCi/kg of 131I-MIBG n=26 Participants The second cohort will be 3-6 patients at the same doses of vincristine and irinotecan and 18 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	Total n=32 Participants Total of all reporting groups
Age, Continuous	12.5 years n=5 Participants	6 years n=7 Participants	6 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	17 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	26 participants n=7 Participants	32 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks

To determine whether doses of 15 mCi/kg and 18 mCi/kg of 131I-MIBG are tolerable when given with irinotecan/vincristine on a 5-day schedule to children and young adults with high-risk refractory/relapsed neuroblastoma.

Outcome measures

Measure	15 mCi/kg of 131I-MIBG n=6 Participants The first cohort for safety will be 3-6 patients treated with vincristine and irinotecan and 15 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	18 mCi/kg of 131I-MIBG n=26 Participants The second cohort will be 3-6 patients at the same doses of vincristine and irinotecan and 18 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	Homozygous UGT1A1*28 Genotype Population homozygous UGT1A1\*28 genotype polymorphisms
Number of Participants With Dose-limiting Toxicity as a Measure of Tolerability	0 participants with DLT	0 participants with DLT	—

SECONDARY outcome

Timeframe: 6 weeks

Therapeutic response rate to regimen according to the NANT modified-version of the International Neuroblastoma Response Criteria.

Outcome measures

Measure	15 mCi/kg of 131I-MIBG n=6 Participants The first cohort for safety will be 3-6 patients treated with vincristine and irinotecan and 15 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	18 mCi/kg of 131I-MIBG n=26 Participants The second cohort will be 3-6 patients at the same doses of vincristine and irinotecan and 18 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	Homozygous UGT1A1*28 Genotype Population homozygous UGT1A1\*28 genotype polymorphisms
Therapeutic Response Rate	3 Participants	6 Participants	—

SECONDARY outcome

Timeframe: One year

Rate of protocol associated diarrhea according to UGT1A1 genotype.

Outcome measures

Measure	15 mCi/kg of 131I-MIBG n=11 Participants The first cohort for safety will be 3-6 patients treated with vincristine and irinotecan and 15 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	18 mCi/kg of 131I-MIBG n=8 Participants The second cohort will be 3-6 patients at the same doses of vincristine and irinotecan and 18 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	Homozygous UGT1A1*28 Genotype n=5 Participants Population homozygous UGT1A1\*28 genotype polymorphisms
Changes in Diarrhea Diarrhoea (any grade)	8 Participants	5 Participants	4 Participants
Changes in Diarrhea Diarrhoea (> grade 2)	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: One year

Population: No PET scans were performed during this trial.

To describe changes in standardized uptake values (SUVs) obtained by 18FDG-PET scan at study entry and in response to one cycle of protocol therapy.

Outcome measures

Outcome data not reported

Adverse Events

15 mCi/kg of 131I-MIBG

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

18 mCi/kg of 131I-MIBG

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	15 mCi/kg of 131I-MIBG n=6 participants at risk The first cohort for safety will be 3-6 patients treated with vincristine and irinotecan and 15 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	18 mCi/kg of 131I-MIBG n=26 participants at risk The second cohort will be 3-6 patients at the same doses of vincristine and irinotecan and 18 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.
General disorders dehydration	0.00% 0/6 • Adverse events were collected over the 6-week observation period. Adverse events were based upon CTCAE.	7.7% 2/26 • Adverse events were collected over the 6-week observation period. Adverse events were based upon CTCAE.

Other adverse events

Measure	15 mCi/kg of 131I-MIBG n=6 participants at risk The first cohort for safety will be 3-6 patients treated with vincristine and irinotecan and 15 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.	18 mCi/kg of 131I-MIBG n=26 participants at risk The second cohort will be 3-6 patients at the same doses of vincristine and irinotecan and 18 mCi/kg of 131I-MIBG. Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.
Gastrointestinal disorders Diarrhea	0.00% 0/6 • Adverse events were collected over the 6-week observation period. Adverse events were based upon CTCAE.	7.7% 2/26 • Adverse events were collected over the 6-week observation period. Adverse events were based upon CTCAE.

Additional Information

Steven DuBois, MD

UCSF Dept of Pediatrics

Phone: 415-476-3831

Email: duboiss@peds.ucsf.ed

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place