Trial Outcomes & Findings for Pazopanib Hydrochloride in Treating Patients With Advanced or Progressive Malignant Pheochromocytoma or Paraganglioma (NCT NCT01340794)

NCT ID: NCT01340794

Last Updated: 2017-09-21

Results Overview

Response and progression are evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1) Ninety-five percent confidence intervals for the true response proportion was calculated using the exact binomial test. Complete Response (CR): All of the following must be true: 1. Disappearance of all target and non-target lesions. 2. Each lymph node must have reduction in short axis to \<1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking baseline measures as reference. Overall Response (OR) was calculated by summing the number of patients with a CR or PR.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2017-09-21

Participant Flow

This study opened on 10/3/2011 and enrolled 2 patients prior to temporarily closing on 2/28/2012 due to safety concerns. After review of AEs, an addendum was implemented which instituted changes to treatment administration, namely, 2 - 14 day run-in periods where patients received pazopanib PO days 1-7 and then were assessed for safety.

A total of seven patients were recruited to this study. One of the 5 patients registered to the study post-addendum cancelled prior to initiating treatment.

Participant milestones

Participant milestones
Measure
Treatment: Pazopanib With no Run-in
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Treatment: Pazopanib Run-in
Cycle 1: Patients receive 400 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 2: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 3 and beyond: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Overall Study
STARTED
2
5
Overall Study
COMPLETED
2
4
Overall Study
NOT COMPLETED
0
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Treatment: Pazopanib With no Run-in
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Treatment: Pazopanib Run-in
Cycle 1: Patients receive 400 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 2: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 3 and beyond: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Overall Study
Withdrawal by Subject
0
1

Baseline Characteristics

Pazopanib Hydrochloride in Treating Patients With Advanced or Progressive Malignant Pheochromocytoma or Paraganglioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment: Pazopanib Without Run-in
n=2 Participants
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Treatment: Pazopanib With Run-in
n=4 Participants
Cycle 1: Patients receive 400 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 2: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 3 and beyond: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Total
n=6 Participants
Total of all reporting groups
Age, Continuous
42 years
n=5 Participants
64.5 years
n=7 Participants
57 years
n=5 Participants
Sex: Female, Male
Female
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Sex: Female, Male
Male
1 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
Region of Enrollment
United States
2 participants
n=5 Participants
4 participants
n=7 Participants
6 participants
n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Population: One of the two patients that initiated treatment with no run-in was found to be ineligible for this endpoint, leaving one patient evaluable for this endpoint in this treatment group. For patient confidentiality, results are not entered for endpoints based on 1 patient measures. All 4 patients that initiated treatment with a run-in were evaluable

Response and progression are evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1) Ninety-five percent confidence intervals for the true response proportion was calculated using the exact binomial test. Complete Response (CR): All of the following must be true: 1. Disappearance of all target and non-target lesions. 2. Each lymph node must have reduction in short axis to \<1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking baseline measures as reference. Overall Response (OR) was calculated by summing the number of patients with a CR or PR.

Outcome measures

Outcome measures
Measure
Treatment: Pazopanib With no Run-in
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Treatment: Pazopanib Run-in
n=4 Participants
Cycle 1: Patients receive 400 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 2: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 3 and beyond: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Response Rate (RR) (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.1
0 percentage of participants
Interval 0.0 to 60.0

SECONDARY outcome

Timeframe: Up to 5 years

Population: One of the two patients that initiated treatment with no run-in was found to be ineligible for this endpoint, leaving one patient evaluable for this endpoint in this treatment group. For patient confidentiality, results are not entered for endpoints based on 1 patient measures. None of the 4 patients that initiated treatment with a run-in responded

Defined for all patients whose tumor met the criteria of CR or PR (using the RECIST criteria) as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: The time from registration to death due to any cause, assessed up to 5 years

Population: One of the two patients that initiated treatment with no run-in was found to be ineligible for this endpoint, leaving one patient evaluable for this endpoint in this treatment group. For patient confidentiality, results are not entered for endpoints based on 1 patient measures. All 4 patients that initiated treatment with a run-in were evaluable

Overall survival time is defined as the time from registration to death due to any cause and will be estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure
Treatment: Pazopanib With no Run-in
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Treatment: Pazopanib Run-in
n=4 Participants
Cycle 1: Patients receive 400 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 2: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 3 and beyond: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Overall Survival Time
14.8 months
Interval 7.6 to 26.3

SECONDARY outcome

Timeframe: The time from registration to documentation of disease progression or death, whichever occurs first, assessed up to 5 years

Population: One of the two patients that initiated treatment with no run-in was found to be ineligible for this endpoint, leaving one patient evaluable for this endpoint in this treatment group. For patient confidentiality, results are not entered for endpoints based on 1 patient measures. All 4 patients that initiated treatment with a run-in were evaluable

Progression-free survival is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. Progression-free survival time will be estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure
Treatment: Pazopanib With no Run-in
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Treatment: Pazopanib Run-in
n=4 Participants
Cycle 1: Patients receive 400 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 2: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 3 and beyond: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Progression-free Survival Time
6.5 months
Interval 2.1 to 26.3

SECONDARY outcome

Timeframe: Up to 5 years from registration

Population: One of the two patients that initiated treatment with no run-in was found to be ineligible for this endpoint, leaving one patient evaluable for this endpoint in this treatment group. For patient confidentiality, results are not entered for endpoints based on 1 patient measures. All 4 patients that initiated treatment with a run-in were evaluable.

The time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 5 years.

Outcome measures

Outcome measures
Measure
Treatment: Pazopanib With no Run-in
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Treatment: Pazopanib Run-in
n=4 Participants
Cycle 1: Patients receive 400 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 2: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-7 of a 14 day cycle. Cycle 3 and beyond: Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Time to Treatment Failure
2.4 months
Interval 0.8 to 5.7

Adverse Events

Treatment: Pazopanib Without Run-in

Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths

Treatment: Pazopanib With Run-in

Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Treatment: Pazopanib Without Run-in
n=2 participants at risk
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Treatment: Pazopanib With Run-in
n=4 participants at risk
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Blood and lymphatic system disorders
Anemia
50.0%
1/2 • Number of events 1
0.00%
0/4
Cardiac disorders
Myocardial infarction
50.0%
1/2 • Number of events 1
0.00%
0/4
Gastrointestinal disorders
Nausea
50.0%
1/2 • Number of events 1
0.00%
0/4
General disorders
Fatigue
50.0%
1/2 • Number of events 1
0.00%
0/4
Investigations
Aspartate aminotransferase increased
50.0%
1/2 • Number of events 1
0.00%
0/4
Investigations
Blood bilirubin increased
50.0%
1/2 • Number of events 1
0.00%
0/4
Investigations
CPK increased
50.0%
1/2 • Number of events 1
0.00%
0/4
Investigations
Cardiac troponin I increased
50.0%
1/2 • Number of events 1
0.00%
0/4
Investigations
GGT increased
50.0%
1/2 • Number of events 1
0.00%
0/4
Investigations
Platelet count decreased
50.0%
1/2 • Number of events 1
0.00%
0/4
Metabolism and nutrition disorders
Hypoalbuminemia
50.0%
1/2 • Number of events 1
0.00%
0/4
Metabolism and nutrition disorders
Hyponatremia
50.0%
1/2 • Number of events 1
0.00%
0/4
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify
50.0%
1/2 • Number of events 1
0.00%
0/4
Musculoskeletal and connective tissue disorders
Bone pain
50.0%
1/2 • Number of events 1
0.00%
0/4
Nervous system disorders
Intracranial hemorrhage
50.0%
1/2 • Number of events 1
0.00%
0/4
Nervous system disorders
Syncope
50.0%
1/2 • Number of events 1
0.00%
0/4
Psychiatric disorders
Confusion
50.0%
1/2 • Number of events 1
0.00%
0/4
Renal and urinary disorders
Hematuria
50.0%
1/2 • Number of events 1
0.00%
0/4
Vascular disorders
Hypertension
50.0%
1/2 • Number of events 1
25.0%
1/4 • Number of events 1
Vascular disorders
Hypotension
50.0%
1/2 • Number of events 1
0.00%
0/4

Other adverse events

Other adverse events
Measure
Treatment: Pazopanib Without Run-in
n=2 participants at risk
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Treatment: Pazopanib With Run-in
n=4 participants at risk
Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28 of a 28 day cycle.
Blood and lymphatic system disorders
Anemia
50.0%
1/2 • Number of events 3
0.00%
0/4
Endocrine disorders
Hypothyroidism
50.0%
1/2 • Number of events 27
25.0%
1/4 • Number of events 1
Gastrointestinal disorders
Abdominal pain
50.0%
1/2 • Number of events 1
0.00%
0/4
Gastrointestinal disorders
Anal pain
50.0%
1/2 • Number of events 1
0.00%
0/4
Gastrointestinal disorders
Diarrhea
50.0%
1/2 • Number of events 28
50.0%
2/4 • Number of events 2
Gastrointestinal disorders
Nausea
50.0%
1/2 • Number of events 14
50.0%
2/4 • Number of events 7
Gastrointestinal disorders
Vomiting
50.0%
1/2 • Number of events 12
25.0%
1/4 • Number of events 1
General disorders
Fatigue
100.0%
2/2 • Number of events 32
100.0%
4/4 • Number of events 15
Investigations
Alanine aminotransferase increased
50.0%
1/2 • Number of events 1
25.0%
1/4 • Number of events 1
Investigations
Alkaline phosphatase increased
50.0%
1/2 • Number of events 19
25.0%
1/4 • Number of events 1
Investigations
Aspartate aminotransferase increased
100.0%
2/2 • Number of events 31
50.0%
2/4 • Number of events 3
Investigations
Blood bilirubin increased
50.0%
1/2 • Number of events 1
0.00%
0/4
Investigations
Electrocardiogram QT corrected interval prolonged
0.00%
0/2
25.0%
1/4 • Number of events 1
Investigations
Hemoglobin increased
50.0%
1/2 • Number of events 1
0.00%
0/4
Investigations
Investigations - Other, specify
50.0%
1/2 • Number of events 1
0.00%
0/4
Investigations
Lymphocyte count decreased
50.0%
1/2 • Number of events 2
0.00%
0/4
Investigations
Neutrophil count decreased
50.0%
1/2 • Number of events 17
0.00%
0/4
Investigations
Platelet count decreased
100.0%
2/2 • Number of events 28
0.00%
0/4
Investigations
White blood cell decreased
100.0%
2/2 • Number of events 25
0.00%
0/4
Metabolism and nutrition disorders
Anorexia
0.00%
0/2
50.0%
2/4 • Number of events 4
Musculoskeletal and connective tissue disorders
Arthralgia
0.00%
0/2
25.0%
1/4 • Number of events 1
Musculoskeletal and connective tissue disorders
Flank pain
0.00%
0/2
25.0%
1/4 • Number of events 1
Nervous system disorders
Dysgeusia
0.00%
0/2
25.0%
1/4 • Number of events 7
Nervous system disorders
Headache
0.00%
0/2
25.0%
1/4 • Number of events 1
Psychiatric disorders
Anxiety
50.0%
1/2 • Number of events 1
0.00%
0/4
Psychiatric disorders
Depression
50.0%
1/2 • Number of events 1
25.0%
1/4 • Number of events 2
Renal and urinary disorders
Hematuria
50.0%
1/2 • Number of events 1
0.00%
0/4
Renal and urinary disorders
Proteinuria
50.0%
1/2 • Number of events 1
25.0%
1/4 • Number of events 6
Skin and subcutaneous tissue disorders
Skin hypopigmentation
100.0%
2/2 • Number of events 33
25.0%
1/4 • Number of events 4
Vascular disorders
Hypertension
100.0%
2/2 • Number of events 32
100.0%
4/4 • Number of events 15

Additional Information

Keith Bible, M.D., Ph.D.

Mayo Clinic Cancer Center

Results disclosure agreements

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

Restriction type: LTE60