Trial Outcomes & Findings for Study of Difluoromethylornithine (DFMO) in Combination With Bortezomib for Relapsed or Refractory Neuroblastoma (NCT NCT02139397)

Last Updated: 2024-08-06

Results Overview

Phase I- To determine the safety and tolerability of DFMO in combination with bortezomib at 3 dose levels of DFMO: 1500mg/m2 twice daily, 2000mg/m2 twice daily, and 2500mg/m2 twice daily in subjects with relapsed or refractory neuroblastoma who receive one full cycle of this dose. Phase II- Study did not enroll to Phase II. Study completed at end of Phase I.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

16 participants

Primary outcome timeframe

Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average 6 months.

Results posted on

2024-08-06

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I: Difluoromethylornithine (DFMO) 1500 mg/m^2 Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase I: DFMO 2000 mg/m^2 Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase I: DFMO 2500 mg/m^2 Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.
Overall Study STARTED	3	7	6
Overall Study COMPLETED	3	7	6
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Difluoromethylornithine (DFMO) in Combination With Bortezomib for Relapsed or Refractory Neuroblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: DFMO 1500 mg/m^2 n=3 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase I: DFMO 2000 mg/m^2" n=7 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase I: DFMO 2500 mg/m^2" n=6 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase 2 The highest tolerated DFMO dose from the Phase I dose escalation will be used for the Phase II portion of the study. Subjects will receive oral DFMO twice daily on each day of this 21-day cycle along with Bortezomib and Etoposide.	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	0 Participants n=4 Participants	16 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	10 years n=5 Participants	7.1 years n=7 Participants	10 years n=5 Participants	—	8.75 years n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	—	5 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	—	11 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	—	2 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	—	13 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	—	1 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	—	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	—	1 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	—	13 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	—	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average 6 months.

Population: All subjects that took at least one dose of DFMO

Outcome measures

Outcome measures
Measure	Phase I: DFMO 1500 mg/m^2 n=3 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase I: DFMO 2000 mg/m^2" n=7 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase I: DFMO 2500 mg/m^2" n=6 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase 2 The highest tolerated DFMO dose from the Phase I dose escalation will be used for the Phase II portion of the study. Subjects will receive oral DFMO twice daily on each day of this 21-day cycle along with Bortezomib and Etoposide.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	2 Participants	1 Participants	3 Participants	—

SECONDARY outcome

Timeframe: Followed until off therapy, generally 1 year

Population: Analyzed population only includes evaluable subjects, defined as subjects that made it to an evaluation time point (disease evaluation scans), or had a documented progression of disease prior to evaluation time point.

To determine the overall response rate (ORR) by the presence of radiologically assessable disease by cross-sectional imaging and in MIBG (meta-iodobenzylguanidine) or PET (positron emission computed tomography) scans. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI imaging and/or by MIBG or PET scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the disease measurements for measurable lesions, Stable Disease, Neither sufficient decrease to qualify for PR or sufficient increase to qualify for PD from study entry. Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Phase I: DFMO 1500 mg/m^2 n=3 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase I: DFMO 2000 mg/m^2" n=5 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase I: DFMO 2500 mg/m^2" n=5 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase 2 The highest tolerated DFMO dose from the Phase I dose escalation will be used for the Phase II portion of the study. Subjects will receive oral DFMO twice daily on each day of this 21-day cycle along with Bortezomib and Etoposide.
Determine the Overall Response Rate (ORR) of Participants Using RECIST Criteria Complete Response	0 Participants	0 Participants	0 Participants	—
Determine the Overall Response Rate (ORR) of Participants Using RECIST Criteria Partial Response	1 Participants	0 Participants	0 Participants	—
Determine the Overall Response Rate (ORR) of Participants Using RECIST Criteria Stable Disease	1 Participants	2 Participants	2 Participants	—
Determine the Overall Response Rate (ORR) of Participants Using RECIST Criteria Progressive Disease	1 Participants	2 Participants	3 Participants	—
Determine the Overall Response Rate (ORR) of Participants Using RECIST Criteria Mixed Response	0 Participants	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: From date of start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

Time to progression (PFS), defined as the period from the start of the treatment until the criteria for progression are met taking as reference the screening measurements. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment (nadir), and minimum 5 mm increase over the nadir or the appearance of one or more new lesions or appearance of positive bone marrow.

Outcome measures

Outcome measures
Measure	Phase I: DFMO 1500 mg/m^2 n=3 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase I: DFMO 2000 mg/m^2" n=6 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase I: DFMO 2500 mg/m^2" n=5 Participants Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.	Phase 2 The highest tolerated DFMO dose from the Phase I dose escalation will be used for the Phase II portion of the study. Subjects will receive oral DFMO twice daily on each day of this 21-day cycle along with Bortezomib and Etoposide.
Determine the Progression Free Survival (PFS) of Participants Using Days Until Progression	108.3 Days Interval 41.0 to 160.0	51.2 Days Interval 23.0 to 84.0	61.8 Days Interval 21.0 to 140.0	—

Adverse Events

Phase I: DFMO 1500 mg/m^2

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Phase I: DFMO 2000 mg/m^2

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Phase I: DFMO 2500 mg/m^2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Phase I: DFMO 1500 mg/m^2 n=3 participants at risk Subjects that received Dose level 1 - 1500 mg/m2 BID	Phase I: DFMO 2000 mg/m^2 n=7 participants at risk Subjects that received Dose level 2 - 2000 mg/m2 BID	Phase I: DFMO 2500 mg/m^2 n=6 participants at risk Subjects that received Dose level 3 - 2500 mg/m2 BID
Gastrointestinal disorders Vomiting	0.00% 0/3 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	14.3% 1/7 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/6 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/7 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	16.7% 1/6 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.

Other adverse events

Other adverse events
Measure	Phase I: DFMO 1500 mg/m^2 n=3 participants at risk Subjects that received Dose level 1 - 1500 mg/m2 BID	Phase I: DFMO 2000 mg/m^2 n=7 participants at risk Subjects that received Dose level 2 - 2000 mg/m2 BID	Phase I: DFMO 2500 mg/m^2 n=6 participants at risk Subjects that received Dose level 3 - 2500 mg/m2 BID
Hepatobiliary disorders Alanine aminotransferase increased	33.3% 1/3 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/7 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/6 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/7 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	16.7% 1/6 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.
Gastrointestinal disorders Anorexia	33.3% 1/3 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	14.3% 1/7 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/6 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/7 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	16.7% 1/6 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.
Gastrointestinal disorders Nausea	0.00% 0/3 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	14.3% 1/7 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	33.3% 2/6 • Number of events 2 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.
Blood and lymphatic system disorders Neutropenia	33.3% 1/3 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/7 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/6 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.
General disorders Pain	0.00% 0/3 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/7 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	16.7% 1/6 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/7 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	16.7% 1/6 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.
Ear and labyrinth disorders Hearing impaired	0.00% 0/3 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/7 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	16.7% 1/6 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.
Nervous system disorders Peripheral sensory neuropathy	33.3% 1/3 • Number of events 1 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/7 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.	0.00% 0/6 • Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.

Additional Information

Giselle Sholler, MD

Beat Childhood Cancer

Phone: 7175310003

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60