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Multiple Endocrine Neoplasia Type 1Phase 2NCT02101918

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

A Phase 2 study testing Computed Tomography Perfusion Imaging, Laboratory Biomarker Analysis and Ziv-Aflibercept in people with Multiple Endocrine Neoplasia Type 1 and Pancreatic Neuroendocrine Carcinoma, run by National Cancer Institute (NCI) at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Computed Tomography Perfusion Imaging, Laboratory Biomarker Analysis and Ziv-Aflibercept
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
3 sitesUnited States
Study dates
18 Jun 2014to 31 Jan 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Patients must have prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) within 1.2 x the upper limit of normal
  • Patients must have resting blood pressure (BP) no greater than 140 mmHg (systolic) or 90 mmHg (diastolic) for eligibility; initiation or adjustment of BP medication is permitted prior to study entry
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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
  • Adverse events (with exception of alopecia, peripheral sensory neuropathy and those listed in specific exclusion criteria) from any prior anti cancer therapy of grade > 1 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] version [v.]4.0)
  • 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
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  • 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
  • History of uncontrolled hypertension, defined as systolic blood pressure > 150 mmHg while simultaneous diastolic blood pressure > 100 mmHg, or systolic blood pressure > 180 mmHg when diastolic blood pressure < 90 mmHg, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment
  • Patients on anticoagulant therapy with unstable dose of warfarin and/or having an out-of- therapeutic range INR (> 3) within the 4 weeks prior to study entry
  • Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g. INR > 1.5 without vitamin K antagonist therapy), non-healing wound

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Moffitt Cancer Center-International Plaza

    Tampa, Florida, 33607

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: Perfusion CT as Predictive Biomarker in a Phase II Study of Ziv-Aflibercept in Patients With Advanced Pancreatic Neuroendocrine Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Estimate the objective response rate (RR) of ziv-aflibercept among patients with advanced pancreatic neuroendocrine tumors (NET)s according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. Test the following hypotheses: that baseline perfusion computed tomography (CT) parameters can predict which patients with advanced pancreatic neuroendocrine tumors (pNETs) will respond to treatment with ziv-aflibercept.

SECONDARY OBJECTIVES:

  1. Estimate progression free survival (PFS) duration among patients treated with ziv-aflibercept.

II. Evaluate the relationship between response rate and baseline blood volume (BV) and between response rate and baseline permeability surface (PS).

TERTIARY OBJECTIVES:

  1. Determine whether post-treatment changes in BV expressed as relative change from baseline correlate with response to ziv-aflibercept.

II. Determine whether post-treatment tumor blood flow (BF) (absolute measurement) correlates with response to ziv-aflibercept.

III. Determine whether post-treatment changes in BF and, BV, expressed as relative change from baseline, correlate with relative change in sum of tumor diameters (RECIST 1.1 measurements).

IV. Determine the effect of ziv-aflibercept therapy on post-treatment blood flow (BF), BV, mean transit time (MTT), and PS at 4 weeks after treatment.

  1. Evaluate the changes in tumor perfusion parameters at time of progression.

OUTLINE:

Patients receive ziv-aflibercept intravenously (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.

After completion of study treatment, patients are followed up periodically.

Being tested
Computed Tomography Perfusion Imaging, Laboratory Biomarker Analysis, Ziv-Aflibercept
Medical subject headings
Multiple Endocrine Neoplasia Type 1, Somatostatinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Computed Tomography Perfusion ImagingRadiation

    Undergo computed tomography perfusion imaging

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Ziv-AfliberceptBiological

    Also called AFLIBERCEPT, AVE0005, Eylea, vascular endothelial growth factor trap

    Given IV

Study groups in NCT02101918
Study groupRoleWhat they receive
Treatment (ziv-aflibercept, perfusion CT)ExperimentalPatients 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.
Receives: Radiation: Computed Tomography Perfusion Imaging; Other: Laboratory Biomarker Analysis; Biological: Ziv-Aflibercept

What is being measured

The primary outcome is the main question the study is designed to answer.

  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,

    Measured: Through study completion an average of 19 months

Secondary outcomes (3)

  1. Progression Free Survival (PFS)

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

    Measured: Through study completion an average of 19 months

  2. Baseline Blood Volume (BV)

    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).

    Measured: Baseline

  3. Baseline Permeability Surface (PS)

    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).

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Apr 2014 (estimated)
  2. Study start18 Jun 2014
  3. Primary completion31 Jan 2018
  4. Study completion31 Jan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02101918
Sponsor's protocol ID
NCI-2014-00642
Other IDs
NCI-2014-00642, 2013-0954, 9604, 9604, N01CM00039, P30CA016672
Status last verified
Mar 2020
First submitted
28 Mar 2014
Last updated
23 Mar 2020
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Computed Tomography Perfusion Imaging, Laboratory Biomarker Analysis and Ziv-Aflibercept in people with Multiple Endocrine Neoplasia Type 1 and Pancreatic Neuroendocrine Carcinoma, run by National Cancer Institute (NCI) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (time frame: Through study completion an average of 19 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02101918.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2020.

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