Back to results

Predictive Biomarkers of Response to Sunitinib in the Treatment of Poorly-differentiated NEURO-Endocrine Tumors (NET)

Primary Purpose

Neuroendocrine Tumors, Pancreatic Neoplasms, Advanced Disease

Status

Terminated

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Sutent

About this trial

This is an interventional treatment trial for Neuroendocrine Tumors focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hôpital Beaujon

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

patient treated

Arm Description

patient who receive sunitinib (SUTENT)

Outcomes

Primary Outcome Measures

Predictive molecular markers of response to sunitinib

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.

Secondary Outcome Measures

The antitumor activity of sunitinib

Objective response according to RECIST criteria (Time Frame: duration of study Safety issue: No). Overall Survival (Time Frame: 6 months. Safety issue: No). Progression-free survival (PFS) Correlation between overall survival, PFS and tumor necrosis assessed on CT scan

Residual concentration

correlation between the concentration of sunitinib and its major active metabolite, SU012662, and objective response and /or toxicity.

Full Information

NCT ID

NCT01215578

First Posted

September 23, 2010

Last Updated

April 29, 2015

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT01215578

Brief Title

Predictive Biomarkers of Response to Sunitinib in the Treatment of Poorly-differentiated NEURO-Endocrine Tumors

Acronym

NET

Official Title

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.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Terminated

Why Stopped

lack of recruitement

Study Start Date

October 2008 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to identify predictive molecular markers of response to continuous daily sunitinib at dose of 37.5 mg used in patients with poorly-differentiated Advanced/Inoperable NEURO-Endocrine Tumors. Hypothesis: To distinguish molecular markers based on their expression at the initial biopsy, their detection by proteomic analysis and demonstrating that tumor or vascular cells are straightaway sensitive to sunitinib (markers sensitivity). The presence of these markers at the initial biopsy predict the sensitivity to sunitinib(Positive predictive value of markers)

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuroendocrine Tumors, Pancreatic Neoplasms, Advanced Disease, Sunitinib

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

patient treated

Arm Type

Experimental

Arm Description

patient who receive sunitinib (SUTENT)

Intervention Type

Drug

Intervention Name(s)

Sutent

Intervention Description

sunitinib 37.5 mg/day (per os) for 6 months

Primary Outcome Measure Information:

Title

Predictive molecular markers of response to sunitinib

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.

Time Frame

1 year

Secondary Outcome Measure Information:

Title

The antitumor activity of sunitinib

Description

Time Frame

1 year

Title

Residual concentration

Description

correlation between the concentration of sunitinib and its major active metabolite, SU012662, and objective response and /or toxicity.

Time Frame

2 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eric Raymond, Professor

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hôpital Beaujon

City

Clichy

State/Province

Hauts de Seine

ZIP/Postal Code

92110

Country

France

12. IPD Sharing Statement

Learn more about this trial

Predictive Biomarkers of Response to Sunitinib in the Treatment of Poorly-differentiated NEURO-Endocrine Tumors

We'll reach out to this number within 24 hrs