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

NCT02101918 | Completed Phase 2 Results

• 5 other identifiers: NCI-2014-006422013-09549604N01CM00039P30CA016672
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies ziv-aflibercept in treating and perfusion computed tomography perfusion imaging in predicting response in patients with pancreatic neuroendocrine tumors that have spread to other parts of the body or cannot be removed by surgery. Ziv-aflibercept may stop the growth of tumor cells by blocking blood flow to the tumor. Diagnostic procedures, such as computed tomography perfusion, imaging may help measure a patient's response to ziv-aflibercept treatment.

Conditions

Multiple Endocrine Neoplasia Type 1; Pancreatic Neuroendocrine Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  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,

  Through study completion an average of 19 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  Through study completion an average of 19 months

• Baseline Blood Volume (BV)

  Baseline

• Baseline Permeability Surface (PS)

  Baseline

Other Outcomes (6)

• Change in BV

  Baseline to 4 weeks after treatment

• Post-treatment Tumor Blood Flow (BF)

  4 weeks after treatment

• Post-treatment Change in BF

  Baseline to 4 weeks after treatment

Study Arms (1)

Treatment (ziv-aflibercept, perfusion CT)

EXPERIMENTAL

Patients receive ziv-aflibercept IV over 60-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography perfusion imaging at baseline, day 21 of course 1, and at time of progression.

Radiation: Computed Tomography Perfusion Imaging; Other: Laboratory Biomarker Analysis; Biological: Ziv-Aflibercept

Interventions

Computed Tomography Perfusion Imaging RADIATION

Undergo computed tomography perfusion imaging

Treatment (ziv-aflibercept, perfusion CT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ziv-aflibercept, perfusion CT)

Ziv-Aflibercept BIOLOGICAL

Given IV

Also known as: AFLIBERCEPT, AVE0005, Eylea, vascular endothelial growth factor trap, VEGF Trap, VEGF Trap R1R2, VEGF-Trap, Zaltrap

Treatment (ziv-aflibercept, perfusion CT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed low or intermediate grade pancreatic NET; patients with neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN1) syndrome will be eligible
• Patients must have unresectable or metastatic disease
• Patients must have at least one measurable site of disease according to RECIST 1.1 that has not been previously irradiated
• Patients must have at least one lesion suitable for perfusion CT; the lesion should be greater than or equal to 3 cm in size in the cranial caudal direction
• Patient must have no contraindication for CT with iodinated contrast
• Patients who are on a somatostatin analogue for control of hormonal syndromes must be on a stable dose (no change in mg dose of long acting octreotide or lanreotide, changes in dosing interval of +/- 1 week is allowed) for 2 months prior to date of study entry
• Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to date of study entry; women who have had menses within the past 2 years, who have not had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy are considered to be of child-bearing potential; patients with elevated human chorionic gonadotropin (hCG) at baseline that is judged to be related to the tumor are eligible if hCG levels do not show the expected doubling when repeated 5-7 days later, or pregnancy has been ruled out by vaginal ultrasound
• Any number of prior lines of systemic anti-neoplastic therapy are allowed; treatment with =\< 1 prior VEGF inhibitor will be allowed
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< 1.5 x institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Urine protein:creatinine ratio =\< 1.0 OR 24-hour urine protein =\< 500 mg (24-hour total urine protein only need be obtained if urine protein:creatinine ratio \< 1.0)

You may not qualify if:

• Less than 28 days elapsed from prior radiotherapy, from prior surgery and prior chemotherapy to the time of randomization; less than 42 days elapsed from prior major surgery to the time of randomization
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) \> 2
• History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease
• Other prior malignancy; adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or any other cancer from which the patient has been disease free for \> 5 years are allowed
• Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to study entry
• Any of the following within 6 months prior to study entry: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack
• Any of the following within 3 months prior to study entry: grade 3-4 gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event
• Occurrence of deep vein thrombosis within 4 weeks, prior to study entry
• Acquired immuno deficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment
• Any severe acute or chronic medical condition, which could impair the ability of the patient to participate to the study or to interfere with interpretation of study results
• Pregnant or breast feeding women; positive pregnancy test (serum or urine beta-human chorionic gonadotropin \[HCG\]) for women of reproductive potential
• Patient with reproductive potential (female and male) who do not agree to use an accepted effective method of contraception (hormonal or barrier methods, abstinence) during the study treatment period and for at least 3 months following completion of study treatment; for female patient enrolled, the following methods of contraception are acceptable: oral contraceptives accompanied by the use of a second method of contraception, or intra uterine device (IUD) or women who are surgically sterile, or women who are post -menopausal or other reasons have no chance of becoming pregnant
• Absence of signed and dated Institutional Review Board-approved patient informed consent from prior to enrollment in the study
• Urine protein-creatinine ratio (UPCR) \> 1 urinalysis or total urine protein \> 500 mg/24 hours (h)
• Serum creatinine \> 1.5 x upper limit of normal (ULN); if creatinine 1.0-1.5 x ULN, creatinine clearance, calculated according to Cockcroft-Gault formula, \< 60 ml/min will exclude the patient

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Moffitt Cancer Center-International Plaza

Tampa, Florida, 33607, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Multiple Endocrine Neoplasia Type 1; Somatostatinoma

Interventions

Cytidine Triphosphate; aflibercept

Condition Hierarchy (Ancestors)

Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Islet Cell; Pancreatic Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases

Intervention Hierarchy (Ancestors)

Cytosine Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Dr. Daniel M. Halperin/ GI Medical Oncology
• Organization: UT MD Anderson Cancer Center

DMHalperin@mdanderson.org

713-792-2828

Study Officials

• Daniel Halperin

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 2, 2014
• Study Start: June 18, 2014
• Primary Completion: January 31, 2018
• Study Completion: January 31, 2018
• Last Updated: March 23, 2020
• Results First Posted: March 23, 2020

Record last verified: 2020-03

Locations

US (3)