A PHASE III RANDOMIZED, DOUBLE-BLIND STUDY OF SUNITINIB (SU011248, SUTENT®) VERSUS PLACEBO IN PATIENTS WITH PROGRESSIVE ADVANCED/METASTATIC WELL-DIFFERENTIATED PANCREATIC ISLET CELL TUMORS

Phase 1

• Conditions: Progressive, advanced/metastatic well-differentiated pancreatic islet cell tumours; MedDRA version: 9.1Level: HLTClassification code 10033632Term: Pancreatic neoplasms

• Registration Number: EUCTR2006-004022-87-GB
• Lead Sponsor: Pfizer Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02-18
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 340

Inclusion Criteria

1. Histologically or cytologically proven diagnosis of well-differentiated pancreatic islet
cell tumor (according to WHO 2000 classification.)19
2. Local, locally-advanced or metastatic disease documented as having shown
progression (per RECIST guidelines) on a scan (CT, MRI, or Octreoscan®) taken
within 12 months prior to baseline compared to a previous scan taken at any time in
the past (ie, patient must have had disease progression within the past year). The
recent scan indicating progression may be used as the screening scan if within 28 days of randomization.
Octreoscan results may be used to document progressive disease prior to study entry, but not for RECIST determination of tumor response during the study.
3. Disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent.
4. Presence of at least one measurable target lesion for further evaluation according to RECIST criteria (contrast enhancing lesion with the largest diameter =20 mm, based
on conventional CT or MRI scan (or =10 mm with spiral CT scan) done within 3 weeks before the start of treatment).
5. Adequate organ function as defined by the following:
• Serum aspartate aminotransferase (AST; serum glutamate-oxalate transferase
[SGOT]) and serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase [SGPT]) =2.5 x upper limit of normal (ULN). If liver function abnormalities are due to underlying malignancy, then AST and ALT may be =5 x ULN
• Total serum bilirubin =1.5 x ULN
• Prothrombin time (PT) and partial thromboplastin time (PTT) =1.5 x ULN
• Serum albumin =3.0 g/dL
• Absolute neutrophil count (ANC) =1500/µL
• Platelets =100,000/µL
• Hemoglobin =9.0 g/dL
• Serum creatinine =1.5 x ULN
6. ECOG Performance status 0 or 1.
7. Life expectancy = 3 months.
8. Age = 18 years.
9. Previous treatments with chemotherapy, loco-regional therapy (eg, chemoembolization) or interferon are permitted providing that toxicity has resolved to < Grade 1 at study entry and that last treatment was at least 4 weeks prior to baseline assessment.
10. Able to swallow oral compound.
11. Signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial prior to enrolment.
12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patients with poorly-differentiated pancreatic neuroendocrine tumors (according to
WHO 2000 classification).19
2. Current treatment with any chemotherapy, chemoembolization therapy, immunotherapy, or investigational anticancer agent other than somatostatin analogues.
3. Prior treatment with any tyrosine kinase inhibitors or anti-VEGF angiogenic
inhibitors. Prior treatment with non-VEGF-targeted angiogenic inhibitors is permitted.
4. Diagnosis of any second malignancy within the last 5 years, except for adequately
treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri.
5. Treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days, respectively prior to study drug administration
6. Pre-existing abnormality of thyroid function with TSH that cannot be maintained in the normal range with medication.
7. Concomitant treatment with therapeutic doses of anticoagulants. Low dose warfarin (Coumadin®) up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed.
8. Unstable systemic diseases including uncontrolled hypertension (>150/100 mmHg
despite optimal medical therapy) or active uncontrolled infections.
9. Current treatment on another clinical trial.
10. Any of the following within the 12 months prior to study drug administration:
myocardial infarction, severe/unstable angina, symptomatic congestive heart failure,
cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
11. Abnormal cardiac function with abnormal 12 lead ECG. Ongoing cardiac
dysrhythmias of NCI CTC grade =2, atrial fibrillation of any grade, or prolongation of the QTc interval to >450 msec for males or >470 msec for females.
12. Symptomatic brain metastases, spinal cord compression, or new evidence of brain or leptomeningeal disease
13. Left ventricular ejection fraction (LVEF) =50% as measured by either multigated
acquisition (MUGA) scan or echocardiogram (ECHO).
14. Currently pregnant or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to starting study drug. Both female and male patients must be surgically sterile or (or postmenopausal for females), or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the
judgment of the investigator or a designated associate, but examples include the
following: for women - implants, injectables, combined oral contraceptives,
intrauterine devices (IUDs), sexual abstinence, or a partner who has been
vasectomized for at least 6 months. For males - having had a vasectomy for at least 6 months, sexual abstinence, or condoms plus spermacide.
15. Positive test for human immunodeficiency virus (HIV) or acquired immunodeficiencysyndrome (AIDS) related illness.
16. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and in
the judgment of the investigator would make the patient inappropriate for entry into
this study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the progression-free survival (PFS) in subjects with pancreatic islet cell tumors treated with sunitinib at a starting dose of 37.5 mg daily (continuous dosing) with those receiving placebo.;Secondary Objective: • To compare overall survival (OS) between subjects receiving sunitinib and those<br>receiving placebo<br>• To compare objective response (OR) rate between subjects receiving sunitinib and those receiving placebo<br>• To compare duration of response (DR) between subjects receiving sunitinib and those receiving placebo among those subjects achieving a response<br>• To assess time to tumor response (TTR) for subjects receiving sunitinib and those<br>receiving placebo<br>• To assess safety and tolerability of sunitinib<br>• Assess patient reported outcomes (PROs);Primary end point(s): Progression Free Survival (PFS) defined as the time from date of randomization to first progression of disease (PD).