A Multicenter Phase II Open Study Coupled With a Translational Assessment of Biomarkers Predictive of Response to Sunitinib in Patients With Poorly-differentiated Advanced/Inoperable NEURO-Endocrine Tumors.
18 Years
N/A
Both
Neuroendocrine Tumors, Pancreatic Neoplasms, Advanced Disease, Sunitinib
Trial Information
A Multicenter Phase II Open Study Coupled With a Translational Assessment of Biomarkers Predictive of Response to Sunitinib in Patients With Poorly-differentiated Advanced/Inoperable NEURO-Endocrine Tumors.
Neuroendocrine tumors (NET) are rare malignancies (1-2% of digestive cancers); and there is,
in recent years, a slow but steady increase in their incidence. Despite the joint efforts of
several research groups, which led to the new WHO classification (2002), the natural history
of the disease remains heterogene and the resistance to conventional cytotoxic treatment
remains the common denominator of these tumors.
Indeed, the prognosis of patients with metastatic disease remains poor despite numerous
treatments (including: IFN, DTIC, 5-FU, doxorubicin, somatostatin analogues, etc.).
None of which showed a benefit in terms of survival. The main therapeutic objective is still
to get a palliative effect on the symptoms and / or limit a few months tumor progression.
There are many publications showing that angiogenesis is one of the major mechanisms of
tumor progression in TNE. But the multiple signaling pathways involved, the existence of
alternative routes and their relationship to apoptosis inducing molecules remain unknown.
Sunitinib is a new molecule in the family of tyrosine kinase inhibitors targeting multiple
receptors which VEGFR, KIT, PDGF-R, FLT3 and RET. Since 2006 year, Sunitinib has been
approved to treat advanced kidney cancer also called advanced renal cell carcinoma (a
typically chemoresistant disease for which there was no active treatment available).
Many retrospective studies in patients showing that the TNE overexpress one or more targets
of sunitinib. In Phase I trial, an antitumor activity has been identified in neuroendocrine
tumors. In a phase II trial including 100 patients with well-differentiated TNE and
carcinoids, sunitinib is associated with a response rate of 10%, and 82% of clinical benefit
in the form of tumor stability.
Currently, an international randomised phase III trial initiated in well differentiated
forms, but no studies are underway for poorly-differentiated TNE.
All of this suggests that sunitinib could represent an important therapeutic option for
moderate, or poorly differentiated inoperable TNE and needs to be explored in this pathology
by identifying predictive biomarkers of response.
Inclusion Criteria:
- Digestive NET histopathologically proven, poorly-differentiated
- Inoperable/advanced NET (Tumor relapse inoperable or metastatic with no surgical
indication).
- Tumor samples should be made available for analysis(diagnostic biopsy, surgical
specimen)
- measurable disease defined by at least one lesion wich can be measured by at least
one dimension :
- equal or superior to 20 mm ( by conventional methods )
- equal or superior to 10 mm (by spiral scan within 28 days before the beginning
of the treatment)
- Performance status WHO ≤ 2.
- Adequate organ function :
- hematology (absolute neutrophil count equal or superior to 1,5 x 10*9/l ,
platelet equal or superior to 100 x 10*9/l),
- clearance of creatinine equal or superior to 60 ml/min),
- AST/ALT ≤ 5 N, PAL ≤ 5 N, total bilirubin ≤ 2N.
- the selected women must be post-menopausal woman or surgically castrated or have to
accept an effective contraception for the duration of the treatment and 3 month
after.Women who are old enough to procreate must have a negative pregnancy test
within the 72 hours of the beginning of the treatment.They must not be pregnant or to
breastfeed.the selected men and theirs partners must be sterile or use an effective
contraception for the duration of the treatment and 3 month after.
Exclusion Criteria:
- Hypersensitivity to sunitinib.
- Contraindication to sunitinib, including uncontrolled hypertension, medical history
of cerebrovascular accident, unstable cardiac pathology despite optimal medical
therapy (myocardial infarction within the 6 months prior to study drug
administration, severe/unstable angina ), active hemorrhagic syndrome or concomitant
treatment with anticoagulants.
- Any severe acute or chronic co-morbid that may compromise to comply with study
participation: uncontrolled infection, symptomatic congestive heart failure, liver
disturbance, chronic renal failure, active gastro-duodenal ulcer (nonexhaustive
list).
- Known brain metastases.
- Diagnosis of any second malignancy within the last 3 years, except for basal cell or
squamous cell skin cancer, or in situ carcinoma of the cervix uteri
- Current treatment on another clinical trial.
- Prior treatment with an investigational agent within 4 weeks.
- Prior treatment with intravenous biphosphonates
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Predictive molecular markers of response to sunitinib
Outcome Description:
to assess the correlation between the expression of biomarkers and CT scan response. Patients are considered as responders when objective response (Partial or complete response) is showed on CT scan.
Outcome Time Frame:
1 year
Safety Issue:
No
Principal Investigator
Eric Raymond, Professor
Investigator Role:
Principal Investigator
Investigator Affiliation:
Assistance Publique - Hôpitaux de Paris
Authority:
France: Ministry of Health
Study ID:
P070145
NCT ID:
NCT01215578
Start Date:
October 2008
Completion Date:
April 2013
Related Keywords:
- Neuroendocrine Tumors
- Pancreatic Neoplasms
- Advanced Disease
- Sunitinib
- Neuroendocrine Tumors
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Neoplasms, Nerve Tissue
- Pancreatic Neoplasms
- Digestive System Neoplasms
- Neoplasms by Site
- Endocrine Gland Neoplasms
- Adenoma, Islet Cell
- Adenocarcinoma
- Carcinoma
- Adenoma
- Digestive System Diseases
- Pancreatic Diseases
- Endocrine System Diseases
- Sunitinib
- Antineoplastic Agents
- Therapeutic Uses
- Pharmacologic Actions
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Physiological Effects of Drugs
- Growth Inhibitors
- Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Neoplasms
- Neuroendocrine Tumors
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