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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Sponsor:
Collaborators:
Pfizer
Ipsen
Information provided by (Responsible Party):
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier:
NCT01731925
First received: November 19, 2012
Last updated: January 9, 2014
Last verified: March 2013
  Purpose

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


Condition Intervention Phase
Carcinoid Tumors
Drug: Lanreotide
Drug: Placebo (for sunitinib)
Drug: Sunitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A RANDOMIZED PHASE II DOUBLE-BLIND TRIAL OF SUNITINIB VERSUS PLACEBO IN COMBINATION WITH LANREOTIDE IN PATIENTS WITH PROGRESSIVE ADVANCED/METASTATIC MIDGUT CARCINOID TUMORS

Resource links provided by NLM:


Further study details as provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: time from date of randomization to first progression of disease (PD) or death for any reason in the absence of documented PD, assessed up to 3 years after the beginning of the study ] [ Designated as safety issue: No ]
    To evaluate the efficacy of the combination of sunitinib malate with lanreotide acetate and of placebo with lanreotide acetate regarding progression-free-survival (PFS) as assessed by the investigator, in patients suffering from progressive, advanced/metastatic midgut carcinoid tumors.


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: time from date of randomization to date of death, assessed up to 3 years after the beginning of the study ] [ Designated as safety issue: No ]
    To evaluate overall survival (OS) in sunitinib- and placebo-treated subjects.

  • Objective response (OR) [ Time Frame: from randomization until disease progression, assessed up to 3 years after the beginning of the study ] [ Designated as safety issue: No ]
    To evaluate objective response (OR) rate in sunitinib- and placebo-treated subjects.

  • Duration of response (DR) [ Time Frame: time from CR or PR to objective tumor progression or to death due to any cause, whichever occurs first, assessed up to 3 years after the beginning of the study ] [ Designated as safety issue: No ]
    To evaluate duration of response (DR) in sunitinib- and placebo-treated subjects in subjects achieving a response.

  • Time to tumor response (TTR) [ Time Frame: time from date of randomization to first documentation of objective tumor response that is subsequently confirmed.assessed up to 3 years after the beginning of the study ] [ Designated as safety issue: No ]
    To assess time to tumor response (TTR) for sunitinib- and placebo-treated subjects.

  • Biological responses [ Time Frame: from baseline to end of treatment, assessed up to 3 years after the beginning of the study ] [ Designated as safety issue: No ]
    To evaluate the best biological responses as assessed using serum chromogranin A and urine 5HIAA for sunitinib- and placebo-treated subjects.

  • Safety [ Time Frame: from visit 1 to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study ] [ Designated as safety issue: No ]
    To assess safety and tolerability of sunitinib in the study population.

  • Quality of life [ Time Frame: From screening to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study ] [ Designated as safety issue: No ]
    To assess Health related Quality of life (EORTC QLQ C-30).


Estimated Enrollment: 104
Study Start Date: December 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Drug: Sunitinib
Sunitinib 37.5 mg daily
Placebo Comparator: 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.
Drug: 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.
Drug: Placebo (for sunitinib)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01731925

Contacts
Contact: Eric RAYMOND, MD/PhD +33 (0)1 40 87 45 45

Locations
France
Hôpital Saint André Recruiting
Bordeaux, France, 33075
Contact: Denis SMITH, MD         
Principal Investigator: Denis Smith, MD         
Hôpital Beaujon Recruiting
Clichy, France, 92118
Contact: Eric RAYMOND, MD, PhD         
Principal Investigator: Eric RAYMOND, MD, PhD         
Hopital Saint Vincent de Paul Recruiting
Lille, France, 59020
Contact: Sophie DOMINGUEZ, MD         
Principal Investigator: Sophie DOMINGUEZ, MD         
Hôpital Edouard Herriot Recruiting
Lyon, France, 69437
Contact: Catherine LOMBARDBOHAS         
Principal Investigator: Catherine LOMBARD-BOHAS, MD         
CHU La Timone Recruiting
Marseille, France, 13005
Contact: Jean-François SEITZ, MD         
Principal Investigator: Jean-François SEITZ, MD         
CHU Cochin Not yet recruiting
Paris, France
Contact: Romain CORIAT, MD         
Principal Investigator: Romain CORIAT         
Hôpital St Antoine Recruiting
Paris, France, 75012
Contact: Leila BENGRINE LEFEVRE, MD         
Principal Investigator: Leila BENGRINE LEFEVRE, MD         
Institut Mutualiste Montsouris Not yet recruiting
Paris, France
Contact: Christophe LOUVET, PhD         
Principal Investigator: Christophe LOUVET, PhD         
CHU Pontchaillou Not yet recruiting
Rennes, France
Contact: Sylvain MANFREDI, MD         
Principal Investigator: Sylvain MANFREDI, MD         
CHU Rouen Not yet recruiting
Rouen, France
Contact: Fréderic DI FIORE, MD         
Principal Investigator: Fréderic DI FIORE, MD         
Sponsors and Collaborators
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Pfizer
Ipsen
Investigators
Principal Investigator: Eric RAYMOND, MD, PhD Hôpital Beaujon
  More Information

No publications provided

Responsible Party: Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier: NCT01731925     History of Changes
Other Study ID Numbers: SUNLAND D12-01, 2012-001098-94
Study First Received: November 19, 2012
Last Updated: January 9, 2014
Health Authority: France: ANSM - French Competent Authority

Keywords provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):
midgut carcinoid tumors
progressive
advanced
metastatic

Additional relevant MeSH terms:
Carcinoid Tumor
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Angiopeptin
Lanreotide
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Cardiovascular Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014