Trial Outcomes & Findings for Ziv-Aflibercept in Treating and Computed Tomography Perfusion Imaging in Predicting Response in Patients With Pancreatic Neuroendocrine Tumors That Are Metastatic or Cannot Be Removed by Surgery (NCT NCT02101918)

NCT ID: NCT02101918

Last Updated: 2020-03-23

Results Overview

90% exact confidence interval was constructed for the overall group. Per Response EvaluationCriteria In SolidTumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR,

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Through study completion an average of 19 months

Results posted on

2020-03-23

Participant Flow

Participant milestones

Participant milestones
Measure	Aflibercept 6 mg /kg IV Aflibercept 6 mg /kg IV every 3 weeks.
Overall Study STARTED	22
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ziv-Aflibercept in Treating and Computed Tomography Perfusion Imaging in Predicting Response in Patients With Pancreatic Neuroendocrine Tumors That Are Metastatic or Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aflibercept 6 mg /kg IV n=22 Participants Aflibercept 6 mg /kg IV every 3 weeks.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants
Age, Continuous	60.3 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 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	0 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants

PRIMARY outcome

Timeframe: Through study completion an average of 19 months

Population: Eligible patients with baseline perfusion CT imaging. One patient from moffitt was a screen fail however 21 patients were evaluable for response and toxicity.

Outcome measures

Outcome measures
Measure	Aflibercept 6 mg /kg IV n=21 Participants Aflibercept 6 mg /kg IV every 3 weeks.
Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	9.5 percentage of participants Interval 1.7 to 27.1

SECONDARY outcome

Timeframe: Through study completion an average of 19 months

Calculated for all eligible participants using the Kaplan Meier method and reported with confidence interval.

Outcome measures

Outcome measures
Measure	Aflibercept 6 mg /kg IV n=21 Participants Aflibercept 6 mg /kg IV every 3 weeks.
Progression Free Survival (PFS)	10.4 months Interval 1.97 to 17.73

SECONDARY outcome

Timeframe: Baseline

Population: Due to low response rate data were not collected

The relationship between response rate and baseline BV will be evaluated. In addition to hypothesis testing using externally generated cut-points, refinement of optimal cut points in baseline BV separating responders and non-responders will be performed. Receiver operating characteristic (ROC) curves will be generated. Response rates of perfusion computed tomography (pCT) subgroups defined by these cut-points will be compared using chi-square test. Response profiles of pCT subgroups defined by these cut-points will be compared using non-parametric test (Wilcoxon rank sum test).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline

Population: Due to low response rate data were not collected

The relationship between response rate and baseline PS will be evaluated. In addition to hypothesis testing using externally generated cut-points, refinement of optimal cut points in baseline PS separating responders and non-responders will be performed. ROC curves will be generated. Response rates of pCT subgroups defined by these cut-points will be compared using chi-square test. Response profiles of pCT subgroups defined by these cut-points will be compared using non-parametric test (Wilcoxon rank sum test).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 4 weeks after treatment

Population: Due to the low response rate, data for blood volume were not collected

Median will be used as cut point for correlation of post-treatment changes in BV expressed as relative change from baseline with response. Response rates will be compared using chi-square test or Fisher's exact test whenever appropriate. Response profiles will be compared using non-parametric test (Wilcoxon rank sum test).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks after treatment

Population: Response rate was too low to power a valid analysis.

Median will be used as cut point for correlation of post-treatment tumor BF (absolute measurement) with response. Response rates will be compared using chi-square test or Fisher's exact test whenever appropriate. Response rates will be compared using chi-square test or Fisher's exact test whenever appropriate.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 4 weeks after treatment

Population: Response rate was too low to power a valid analysis.

Continuous parameters in relative change in pCT parameters will be plotted against best relative change in sum of tumor diameters from RECIST 1.1 tumor measurements. Pearson correlation will be used to test statistical significance. Non-parametric test will be used if appropriate.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 4 weeks after treatment

Population: Response rate was too low to power a valid analysis.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 4 weeks after treatment

Population: Response rate was too low to power a valid analysis.

The effect of ziv-aflibercept therapy on post-treatment BF, BV, mean transit time, and PS will be determined. Descriptive statistics of pre and post treatment values will be given. Distribution of pre and post treatment values will be graphed. Treatment induced change in values will be compared using paired-t test. Non-parametric test will be used if appropriate.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 1 year

Population: No patients underwent perfusion CT at time of progression, no analysis could not be performed.

Outcome measures

Outcome data not reported

Adverse Events

Aflibercept 6 mg /kg IV

Serious events: 4 serious events

Other events: 21 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Aflibercept 6 mg /kg IV n=22 participants at risk Aflibercept 6 mg /kg IV every 3 weeks.
Gastrointestinal disorders Pain Abdominal	4.5% 1/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Blood and lymphatic system disorders Hemorrhage Upper GI	4.5% 1/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Gastrointestinal disorders cholecystitis	4.5% 1/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Metabolism and nutrition disorders Dehydration	4.5% 1/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.

Other adverse events

Other adverse events
Measure	Aflibercept 6 mg /kg IV n=22 participants at risk Aflibercept 6 mg /kg IV every 3 weeks.
Gastrointestinal disorders Abdominal pain	22.7% 5/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Investigations Alanine aminotransferase increased	18.2% 4/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Blood and lymphatic system disorders Anemia	13.6% 3/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Metabolism and nutrition disorders Anorexia	13.6% 3/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Musculoskeletal and connective tissue disorders Arthralgia	18.2% 4/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Investigations Aspartate aminotransferase increased	13.6% 3/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Gastrointestinal disorders Constipation	22.7% 5/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Investigations Creatinine increased	13.6% 3/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Gastrointestinal disorders Diarrhea	18.2% 4/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Respiratory, thoracic and mediastinal disorders Epistaxis	13.6% 3/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
General disorders Fatigue	27.3% 6/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Nervous system disorders Headache	68.2% 15/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Respiratory, thoracic and mediastinal disorders Hoarseness	40.9% 9/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Vascular disorders Hypertension	77.3% 17/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Gastrointestinal disorders Mucositis oral	45.5% 10/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Gastrointestinal disorders Nausea	22.7% 5/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Investigations Neutrophil count decreased	13.6% 3/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
General disorders Pain	13.6% 3/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	13.6% 3/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Blood and lymphatic system disorders Platelet count decreased	13.6% 3/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Renal and urinary disorders Proteinuria	31.8% 7/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Respiratory, thoracic and mediastinal disorders Sinusitis	9.1% 2/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	4.5% 1/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Gastrointestinal disorders Vomiting	22.7% 5/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.
Metabolism and nutrition disorders Weight loss	13.6% 3/22 • C1D1 and for 30 days after the last dose of study drug. Patients will be followed until resolution or stabilization of the adverse event.

Additional Information

Dr. Daniel M. Halperin/ GI Medical Oncology

UT MD Anderson Cancer Center

Phone: 713-792-2828

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60