Trial Outcomes & Findings for Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma (NCT NCT00843037)
NCT ID: NCT00843037
Last Updated: 2024-10-17
Results Overview
The primary endpoint of this study was disease control rate (DCR) defined as a partial response (PR), complete response (CR), or stable disease maintained for ≥12 weeks from the initiation of treatment. Tumour response to sunitinib was assessed as per RECIST 1.1 using CT-imaging. Clinically apparent lesions needed to be \>10mm by calliper measurement to be included as targets. The primary endpoint was met despite closing to accrual early.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Every 12 weeks (2 cycles) up to disease progression or study discontinuation (an average of 13.5 6-week cycles or about 1.5 years).
Results posted on
2024-10-17
Participant Flow
Patients were enrolled between May 2009 and May 2016 from three centres within Canada and one in the Netherlands.
25 of the planned 28 patients were enrolled
Participant milestones
| Measure |
Single-Arm, Open Label - Sunitinib
Sunitinib: 50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
|
|---|---|
|
Overall Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
24
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Single-Arm, Open Label - Sunitinib
Sunitinib: 50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
|
|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma
Baseline characteristics by cohort
| Measure |
Single-Arm, Open Label - Sunitinib
n=25 Participants
Sunitinib: 50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
|
|---|---|
|
Age, Continuous
|
50 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
24 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
1 participants
n=5 Participants
|
|
Histology
Paraganglionoma
|
11 Participants
n=5 Participants
|
|
Histology
Pheochromocytoma
|
14 Participants
n=5 Participants
|
|
Prior Systemic Therapy
Systemic adjuvant
|
1 Participants
n=5 Participants
|
|
Prior Systemic Therapy
Systemic advanced
|
3 Participants
n=5 Participants
|
|
Prior Systemic Therapy
None
|
21 Participants
n=5 Participants
|
|
Prior Local Therapy
Radiation only
|
4 Participants
n=5 Participants
|
|
Prior Local Therapy
Surgery only
|
11 Participants
n=5 Participants
|
|
Prior Local Therapy
Surgery and radiation
|
5 Participants
n=5 Participants
|
|
Prior Local Therapy
None
|
5 Participants
n=5 Participants
|
|
Stage
Metastatic
|
23 Participants
n=5 Participants
|
|
Stage
Locally advanced
|
2 Participants
n=5 Participants
|
|
Sites of Mestastases
Lymph Nodes
|
11 participants
n=5 Participants
|
|
Sites of Mestastases
Lung
|
12 participants
n=5 Participants
|
|
Sites of Mestastases
Bone
|
12 participants
n=5 Participants
|
|
Sites of Mestastases
Liver
|
14 participants
n=5 Participants
|
|
Total Baseline Urine Metanephrines Elevated
Yes
|
15 Participants
n=5 Participants
|
|
Total Baseline Urine Metanephrines Elevated
No
|
6 Participants
n=5 Participants
|
|
Total Baseline Urine Metanephrines Elevated
Missing
|
4 Participants
n=5 Participants
|
|
Reason for Enrollment
Radiologic and/or biochemical PD
|
20 Participants
n=5 Participants
|
|
Reason for Enrollment
Symptomatic PD
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Every 12 weeks (2 cycles) up to disease progression or study discontinuation (an average of 13.5 6-week cycles or about 1.5 years).Population: Twenty-three patients were evaluable for response.
The primary endpoint of this study was disease control rate (DCR) defined as a partial response (PR), complete response (CR), or stable disease maintained for ≥12 weeks from the initiation of treatment. Tumour response to sunitinib was assessed as per RECIST 1.1 using CT-imaging. Clinically apparent lesions needed to be \>10mm by calliper measurement to be included as targets. The primary endpoint was met despite closing to accrual early.
Outcome measures
| Measure |
Single-Arm, Open Label - Sunitinib
n=23 Participants
Sunitinib: 50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
|
|---|---|
|
Clinical Benefit Rate (CBR) Which is Defined as Either a Partial Response (PR) Complete Response (CR) or Stable Disease (SD) for ≥ 12 Weeks Measured Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
CR, PR, SD > 12 weeks
|
19 Participants
|
|
Clinical Benefit Rate (CBR) Which is Defined as Either a Partial Response (PR) Complete Response (CR) or Stable Disease (SD) for ≥ 12 Weeks Measured Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
Not CR, PR, SD > 12 weeks
|
4 Participants
|
SECONDARY outcome
Timeframe: Within 7 days of study registration and every 12 weeks (2 cycles) up to treatment discontinuation (an average of 13.5 6-week cycles or about 1.5 years).Population: Includes patients that had F/U measurements.
Biochemical and symptom changes: timed urinary catecholamine collection over 24 h included measurements of norepinephrine, epinephrine, dopamine and total metanephrines.
Outcome measures
| Measure |
Single-Arm, Open Label - Sunitinib
n=16 Participants
Sunitinib: 50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
|
|---|---|
|
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
24-h urinary metanephrines · BCR >20% decline in values > 12 weeks
|
7 Participants
|
|
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
norepinephrine · No BCR >20% decline in values > 12 weeks
|
5 Participants
|
|
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
Epinephrine · BCR >20% decline in values > 12 weeks
|
4 Participants
|
|
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
24-h urinary metanephrines · No BCR >20% decline in values > 12 weeks
|
5 Participants
|
|
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
norepinephrine · BCR >20% decline in values > 12 weeks
|
7 Participants
|
|
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
Epinephrine · No BCR >20% decline in values > 12 weeks
|
1 Participants
|
|
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
Dopamine · BCR >20% decline in values > 12 weeks
|
3 Participants
|
|
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
Dopamine · No BCR >20% decline in values > 12 weeks
|
2 Participants
|
|
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
Catecholamines (all) · BCR >20% decline in values > 12 weeks
|
11 Participants
|
|
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
Catecholamines (all) · No BCR >20% decline in values > 12 weeks
|
5 Participants
|
SECONDARY outcome
Timeframe: From time of enrollment until loss to follow-up or death (approximately 125 months for longest patient on treatment).The median overall survival
Outcome measures
| Measure |
Single-Arm, Open Label - Sunitinib
n=25 Participants
Sunitinib: 50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
|
|---|---|
|
Overall Survival
|
112 months
Interval 25.8 to
Insufficient number of participants with events.
|
SECONDARY outcome
Timeframe: Every 12 weeks (2 cycles) up to disease progression or study discontinuation (an average of 13.5 6-week cycles or about 1.5 years).Population: Includes patients that had a PFS event (up to 31 Jan 2018).
Median Progression-Free Survival (PFS)
Outcome measures
| Measure |
Single-Arm, Open Label - Sunitinib
n=21 Participants
Sunitinib: 50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
|
|---|---|
|
Time to Progression
|
13.4 months
Interval 5.3 to 24.6
|
SECONDARY outcome
Timeframe: Every 12 weeks (2 cycles) up to disease progression or study discontinuation (an average of 13.5 6-week cycles or about 1.5 years).Population: 23 evaluable for response data
Overall response rate (PR) + (CR) of participants
Outcome measures
| Measure |
Single-Arm, Open Label - Sunitinib
n=23 Participants
Sunitinib: 50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
|
|---|---|
|
Overall Response Rate (PR) + (CR)
CR+PR
|
3 Participants
|
|
Overall Response Rate (PR) + (CR)
Not CR or PR
|
20 Participants
|
Adverse Events
Single-Arm, Open Label - Sunitinib
Serious events: 10 serious events
Other events: 25 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Single-Arm, Open Label - Sunitinib
n=25 participants at risk
Sunitinib: 50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Blood and lymphatic system disorders
Anemia
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Cardiac disorders
Cardiac ischemia/infarction
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Cardiac disorders
Cardiomyopathy
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Psychiatric disorders
Confusion
|
8.0%
2/25 • Number of events 3 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
General disorders
Death due to Progressive Disease
|
8.0%
2/25 • Number of events 2 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Cardiac disorders
Decompensated Heart Failure
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Metabolism and nutrition disorders
Dehydration
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Renal and urinary disorders
Elevated Creatinine/Renal failure
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
General disorders
Fever
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
General disorders
Generalized Edema
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Cardiac disorders
Heart Failure
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Vascular disorders
Hypertension crisis
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Metabolism and nutrition disorders
Hyponatremia
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Vascular disorders
Hypotension and Electrolyte disorder
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Gastrointestinal disorders
Ileus secondary to adherence
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Infections and infestations
Infection with normal ANC - urinary tract
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Vascular disorders
Left Renal Vein Thrombosis
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Gastrointestinal disorders
Vomiting
|
8.0%
2/25 • Number of events 2 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Vascular disorders
Pulmonary Emboli
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Gastrointestinal disorders
Nausea
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Renal and urinary disorders
Renal Colic
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Cardiac disorders
Tachycardia, Palpitations
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Musculoskeletal and connective tissue disorders
Uncontrolled Bone Pain
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Gastrointestinal disorders
Upper GI Toxicity Post Radiotherapy
|
4.0%
1/25 • Number of events 1 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
Other adverse events
| Measure |
Single-Arm, Open Label - Sunitinib
n=25 participants at risk
Sunitinib: 50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
|
|---|---|
|
General disorders
Fatigue
|
68.0%
17/25 • Number of events 48 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Gastrointestinal disorders
Nausea/Vomiting
|
64.0%
16/25 • Number of events 64 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Skin and subcutaneous tissue disorders
palmar-plantar erythrodysesthesia (PPES)
|
64.0%
16/25 • Number of events 56 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Gastrointestinal disorders
Diarrhea
|
44.0%
11/25 • Number of events 31 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Vascular disorders
Hypertension
|
44.0%
11/25 • Number of events 23 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Gastrointestinal disorders
Mucositis
|
40.0%
10/25 • Number of events 12 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Nervous system disorders
Dysgeusia
|
28.0%
7/25 • Number of events 12 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Metabolism and nutrition disorders
Anorexia
|
20.0%
5/25 • Number of events 11 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Investigations
Thrombocytopenia
|
24.0%
6/25 • Number of events 52 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Investigations
AST/ALT increased
|
12.0%
3/25 • Number of events 11 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Blood and lymphatic system disorders
Anemia
|
12.0%
3/25 • Number of events 15 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Endocrine disorders
Hypothyroidism
|
12.0%
3/25 • Number of events 4 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
|
Investigations
Neutropenia
|
12.0%
3/25 • Number of events 31 • From time of enrollment to 28 days post-discontinuation of treatment, with ongoing protocol-related toxicities and late toxicities followed until loss to follow-up or death (approximately 125 months for longest patient on treatment).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place