A Study of Sunitinib Versus Placebo in Combination With Lanreotide in Patients With Progressive Advanced/Metastatic Midgut Carcinoid Tumors

NCT ID: NCT01731925

Last Updated: 2017-01-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-07
• Study Completion Date: 2017-12-31

Brief Summary

Sunitinib may provide an opportunity for a novel therapeutic strategy for the treatment of subjects with neuroendocrine tumors.

Detailed Description

With the exception of surgery for localized disease, there is presently a lack of available therapies with proven survival benefit for patients with neuroendocrine tumors (NET). Available treatment options for unresectable disease include the use of somatostatin analogs, which may relieve symptoms related to hormonal hypersecretion. The efficacy of cytotoxic chemotherapy in patients with metastatic carcinoid tumors is also limited. Combinations of either streptozocin and cyclophosphamide, or streptozocin and 5-fluorouracil, appear to be inactive, and both regimens are associated with substantial toxicity.

Receptor tyrosine kinases (RTKs) are implicated in deregulated/ autocrine proliferation and survival of solid and hematologic cancer cells. Sunitinib malate is an orally administered small molecule that inhibits the tyrosine kinase enzymatic activities of the receptors for VEGF and PDGF, and also blocks signalling through the KIT, FLT3 and RET pathways.

Therefore, sunitinib malate may provide an opportunity for a novel therapeutic strategy for the treatment of subjects with NET.

Conditions

Carcinoid Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sunitinib

Sunitinib 37.5 mg daily. Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.

Group Type: EXPERIMENTAL

Lanreotide

Intervention Type: DRUG

Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.

Sunitinib

Intervention Type: DRUG

Sunitinib 37.5 mg daily

Placebo

Placebo (for sunitinib). Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.

Group Type: PLACEBO_COMPARATOR

Lanreotide

Intervention Type: DRUG

Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.

Placebo (for sunitinib)

Intervention Type: DRUG

Interventions

Lanreotide

Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.

Intervention Type: DRUG

Placebo (for sunitinib)

Intervention Type: DRUG

Sunitinib

Sunitinib 37.5 mg daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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. 5HIAA levels superior to 1.5ULN as measured in each individual centre.

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 RECIST v1.1

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 enrollment.

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).

Exclusion Criteria

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 equal 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 randomization.

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 randomization.

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 uteri.

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 infections.

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 leptomeningeal disease.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Ipsen

INDUSTRY

Sponsor Role: collaborator

GERCOR - Multidisciplinary Oncology Cooperative Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pascal HAMMEL, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Beaujon

Locations

Cliniques Universitaires Saint Luc

Brussels, , Belgium

Institut Jules Bordet

Brussels, , Belgium

ULB Erasme

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

UZ Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

Hôpital Saint André

Bordeaux, , France

Hôpital Beaujon

Clichy, , France

Hôpital Henri Mondor

Créteil, , France

Hopital Saint Vincent de Paul

Lille, , France

Hôpital Edouard Herriot

Lyon, , France

CHU La Timone

Marseille, , France

Hôpital St Antoine

Paris, , France

CHU Cochin

Paris, , France

Hôpital Pitié Salpêtrière

Paris, , France

Institut Mutualiste Montsouris

Paris, , France

CHU Robert Debré

Reims, , France

CHU Pontchaillou

Rennes, , France

CHU Rouen

Rouen, , France

CHRU Trousseau

Tours, , France

Countries

Belgium; France

Other Identifiers

2012-001098-94

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SUNLAND D12-01

Identifier Type: -

Identifier Source: org_study_id