A RANDOMIZED PHASE II DOUBLE-BLIND TRIAL OF SUNITINIB VERSUS PLACEBO IN COMBINATION WITH LANREOTIDE IN PATIENTS WITH PROGRESSIVE ADVANCED/METASTATIC MIDGUT CARCINOID TUMORS
1. Patients with midgut well-differentiated Grade 1-2 endocrine tumor.
2. Local, locally advanced or metastatic disease documented as progressive by RECIST
v1.1. on CT-scan or MRI at baseline and within 12 months prior to baseline.
3. Chromogranin A and 5HIAA levels superior to 1.5ULN as measured in each individual
4. Disease that is not amenable to surgery with curative intent.
5. Presence of at least one measurable target lesion for further evaluation according to
6. Adequate organ function
7. ECOG Performance status 0 or 1.
8. Life expectancy superior or equal to 3 months.
9. Age superior or equal to 18 years.
10. Female patients must be surgically sterile or be postmenopausal, or must agree to use
effective contraception during the period of therapy. All female patients with
reproductive potential must have a negative pregnancy test (serum or urine) within 7
days prior to enrollment. Breast feeding is not allowed. Male patients must be
surgically sterile 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 principal investigator or a designated associate.
11. Able to swallow oral compound.
12. Signed and dated informed consent document indicating that the patient has been
informed of all pertinent aspects of the trial prior to enrolment.
13. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other study procedures.
14. Registration in a national health care system (CMU included).
1. Patients with undifferentiated, poorly differentiated gastrointestinal neuroendocrine
tumors, pancreatic neuroendocrine tumors, bronchial carcinoid tumors.
2. Patients with carcinoid tumors with the presence of an obstructive intestinal tumor.
3. Patients with uncontrolled cardiac complication as part of their carcinoid syndrome.
4. Current treatment with any chemotherapy, chemoembolization therapy, immunotherapy, or
investigational anticancer agent
5. Current treatment with dose superior or eaqual to 120 mg per month of lanreotide
6. Prior treatment with any tyrosine kinase inhibitors or anti-VEGF angiogenic
inhibitors. Prior treatment with non-VEGF-targeted angiogenic inhibitors such as
everolimus or temsirolimus is permitted.
7. Patients who stopped everolimus treatment was less than 4 weeks prior to
8. Patients with concomitant treatment with interferon.
9. Patients previously treated with chemotherapy, loco-regional therapy (e.g.,
chemoembolization) or interferon with last administration less than 6 weeks prior to
randomization or with toxicity not resolved to less or equal grade 1 at
10. 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
11. Treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days,
respectively prior to study drug administration.
12. Concomitant treatment with therapeutic doses of anticoagulants
13. Concomitant treatment with a drug having proarrhythmic potential
14. Unstable systemic diseases including uncontrolled hypertension or active uncontrolled
15. Current treatment on another clinical trial.
16. 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.
17. Ongoing cardiac dysrhythmias of NCI CTC grade superior or equal to 2, atrial
fibrillation of any grade, or prolongation of the QTc interval to more than 450 msec
for males or more than 470 msec for females.
18. Symptomatic brain metastases, spinal cord compression, or new evidence of brain or
19. Left ventricular ejection fraction inferior or equal 50% as measured by either
multigated acquisition scan or echocardiogram.
20. Positive test for human immunodeficiency virus (HIV) or acquired immunodeficiency
syndrome (AIDS) related illness.
21. Patients with complicated, untreated lithiasis of the bile ducts
22. 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.