Trial Outcomes & Findings for Phase 1 Study of Iobenguane (MIBG) I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma (NCT NCT00458952)

Last Updated: 2016-07-13

Results Overview

Although no primary efficacy endpoint was defined for this study, the MTD of Ultratrace iobenguane I 131 in patients with malignant pheochromocytoma/paraganglioma (a safety rather than an efficacy parameter) is the primary objective.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

24 participants

Primary outcome timeframe

6 weeks post therapy dose

Results posted on

2016-07-13

Participant Flow

24 patients with confirmed pheochromocytoma/paraganglioma were recruited for participation in the trial at 3 US sites. 21 patients received Ultratrace Iobenguane I 131 while 3 patients failed to meet all inclusion/exclusion criteria and were therefore not dosed.

Planned Doses: 6, 7, 8 \& 9 mCi/kg. Dose reductions in 7, 8 \& 9 mCi/kg cohorts were made so total activity administered to pts would not greatly exceed allowed total activity of 525, 600, \& 675 mCi for these groups, respectively. Thus, pts were subsequently analyzed in 2 groups of ≤500 mCi and \>500mCi, consisting of 7 \& 14 patients, respectively.

Participant milestones

Participant milestones
Measure	=< 500 mCi Ultratrace Iobenguane I 131 7 subjects received a mean dose less than or equal to 500 mCi of Ultratrace Iobenguane I 131	>500 mCi 14 subjects received a mean dose of greater than 500 mCi of Ultratrace Iobenguane I 131
Overall Study STARTED	7	14
Overall Study COMPLETED	5	9
Overall Study NOT COMPLETED	2	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 1 Study of Iobenguane (MIBG) I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	=< 500 mCi Ultratrace Iobenguane I 131 n=7 Participants 7 subjects received a mean dose less than or equal to 500 mCi of Ultratrace Iobenguane I 131	>500 mCi n=14 Participants 14 subjects received a mean dose of greater than 500 mCi of Ultratrace Iobenguane I 131	Total n=21 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=99 Participants	12 Participants n=107 Participants	18 Participants n=206 Participants
Age, Categorical >=65 years	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Age, Continuous	46.4 years STANDARD_DEVIATION 15.99 • n=99 Participants	52.4 years STANDARD_DEVIATION 11.41 • n=107 Participants	50.4 years STANDARD_DEVIATION 13.02 • n=206 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	3 Participants n=107 Participants	5 Participants n=206 Participants
Sex: Female, Male Male	5 Participants n=99 Participants	11 Participants n=107 Participants	16 Participants n=206 Participants
Region of Enrollment United States	7 participants n=99 Participants	14 participants n=107 Participants	21 participants n=206 Participants

PRIMARY outcome

Timeframe: 6 weeks post therapy dose

Population: 24 patients with confirmed pheochromocytoma/paraganglioma were recruited for participation in this trial. Of the 24 consenting patients, 21 patients were administered Ultratrace iobenguane I 131. Three patients did not meet all the inclusion and exclusion criteria, and were not allowed into the study.

Outcome measures

Outcome measures
Measure	Ultratrace Iobenguane I 131 n=21 Participants Each patient was to first receive an imaging dose of 5 mCi of Ultratrace iobenguane I 131 to confirm tumor uptake of the test article. If at least one tumor on a baseline CT/MRI scan was also visualized on the Ultratrace iobenguane I 131 scan, the patient was administered a therapeutic dose of Ultratrace iobenguane I 131. Dosing began at 6 mCi/kg for an initial cohort of 3 patients, and escalated in 1.0 mCi/kg increments until the MTD was established.
MTD of Ultratrace Iobenguane I 131	8 mCi/kg

Adverse Events

Ultratrace Iobenguane I 131

Serious events: 15 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ultratrace Iobenguane I 131 n=21 participants at risk Each patient was to first receive an imaging dose of 5 mCi of Ultratrace iobenguane I 131 to confirm tumor uptake of the test article. If at least one tumor on a baseline CT/MRI scan was also visualized on the Ultratrace iobenguane I 131 scan, the patient was administered a therapeutic dose of Ultratrace iobenguane I 131. Dosing began at 6 mCi/kg for an initial cohort of 3 patients, and escalated in 1.0 mCi/kg increments until the MTD was established.
General disorders Chest pain	4.8% 1/21
Vascular disorders Deep vein thrombosis	4.8% 1/21
Nervous system disorders Spinal disorder	4.8% 1/21
General disorders Non-cardiac chest pain	4.8% 1/21
Metabolism and nutrition disorders Dehydration	9.5% 2/21
Gastrointestinal disorders Ileus	4.8% 1/21
Vascular disorders Pulmonary embolism	4.8% 1/21
Nervous system disorders Thalamic infarction	4.8% 1/21
Investigations Platelet count decreased	4.8% 1/21 • Number of events 2
Gastrointestinal disorders Gastrointestinal obstruction	4.8% 1/21
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	4.8% 1/21
Blood and lymphatic system disorders Neutropenia	4.8% 1/21
Musculoskeletal and connective tissue disorders Muscular weakness	4.8% 1/21
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis	14.3% 3/21
Blood and lymphatic system disorders Pancytopenia	4.8% 1/21

Other adverse events

Other adverse events
Measure	Ultratrace Iobenguane I 131 n=21 participants at risk Each patient was to first receive an imaging dose of 5 mCi of Ultratrace iobenguane I 131 to confirm tumor uptake of the test article. If at least one tumor on a baseline CT/MRI scan was also visualized on the Ultratrace iobenguane I 131 scan, the patient was administered a therapeutic dose of Ultratrace iobenguane I 131. Dosing began at 6 mCi/kg for an initial cohort of 3 patients, and escalated in 1.0 mCi/kg increments until the MTD was established.
General disorders Fatigue	66.7% 14/21
General disorders Asthenia	19.0% 4/21
General disorders Injection site irritation	14.3% 3/21
General disorders Edema peripheral	14.3% 3/21
General disorders Pyrexia	14.3% 3/21
Blood and lymphatic system disorders Leukopenia	47.6% 10/21
Blood and lymphatic system disorders Neutropenia	42.9% 9/21
Blood and lymphatic system disorders Thrombocytopenia	47.6% 10/21
Blood and lymphatic system disorders Anemia	42.9% 9/21
Musculoskeletal and connective tissue disorders Back pain	23.8% 5/21
Musculoskeletal and connective tissue disorders Pain in extremity	19.0% 4/21
Musculoskeletal and connective tissue disorders Pain in jaw	14.3% 3/21
Investigations Platelet count decreased	38.1% 8/21
Investigations White blood cell count decreased	28.6% 6/21
Investigations Neutrophil	23.8% 5/21
Investigations Blood thyroid stimulating hormone decreased	19.0% 4/21
Investigations Hemoglobin decreased	19.0% 4/21
Investigations Blood glucose increased	14.3% 3/21
Investigations Hematocrit decreased	14.3% 3/21
Metabolism and nutrition disorders Anorexia	38.1% 8/21
Metabolism and nutrition disorders Dehydration	4.8% 1/21
Nervous system disorders Headache	28.6% 6/21
Nervous system disorders Ageusia	23.8% 5/21
Nervous system disorders Dizziness	14.3% 3/21
Respiratory, thoracic and mediastinal disorders Cough	23.8% 5/21
Respiratory, thoracic and mediastinal disorders Epistaxis	19.0% 4/21
Skin and subcutaneous tissue disorders Alopecia	23.8% 5/21
Vascular disorders Hypotension	14.3% 3/21

Additional Information

Senior Director, Clinical Science Communications

Progenics Pharmaceuticals, Inc.

Phone: 914 784-1825

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60