Neuroendocrine TumorsPhase 2NETNCT01215578
Predictive Biomarkers of Response to Sunitinib in the Treatment of Poorly-differentiated NEURO-Endocrine Tumors
A Phase 2 study testing Sutent in people with Neuroendocrine Tumors and Pancreatic Neoplasms, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumors, Pancreatic Neoplasms, Advanced Disease
- What is being tested?
- Sutent
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2008to Dec 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 12Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
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)
Read the 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.
- Being tested
- Sutent
- 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
- Medical subject headings
- Neuroendocrine Tumors, Pancreatic Neoplasms, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms, Nerve Tissue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SutentDrug
sunitinib 37.5 mg/day (per os) for 6 months
| Study group | Role | What they receive |
|---|---|---|
| patient treated | Experimental | patient who receive sunitinib (SUTENT) Receives: Drug: Sutent |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (2)
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
Measured: 1 year
Residual concentration
correlation between the concentration of sunitinib and its major active metabolite, SU012662, and objective response and /or toxicity.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2010 (estimated)
- Study startOct 2008
- Primary completionDec 2013
- Study completionDec 2014
Why it stopped: lack of recruitement
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine TumorsStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric Raymond, Professor, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01215578
- Sponsor's protocol ID
- P070145
- Other IDs
- 2007-005628-34
- Acronym
- NET
- Status last verified
- Apr 2015
- First submitted
- 23 Sep 2010
- Last updated
- 30 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01215578
- Acronym / sponsor ID
- NET / P070145
- Keywords
- Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms, Nerve Tissue, Pancreatic Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of recruitement
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Oct 2008
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 6 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patient treated | Experimental | Drug: Sutentpatient who receive sunitinib (SUTENT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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 :
- Performance status WHO ≤ 2.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sutentsunitinib 37.5 mg/day (per os) for 6 months | Drug | patient treated |
Primary outcome
Predictive molecular markers of response to sunitinib
Time frame: 1 year
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.
2 secondary outcomes
The antitumor activity of sunitinib
Time frame: 1 year
Residual concentration
Time frame: 2 months
Results and safety
The study was stopped early (reason given: lack of recruitement). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Raymond, Professor principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sutent in people with Neuroendocrine Tumors and Pancreatic Neoplasms, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: lack of recruitement). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Predictive molecular markers of response to sunitinib (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2015.