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Trial record 31 of 913 for:    Advanced | Neuroendocrine Tumors

Efficacy and Safety of Everolimus and (STZ-5FU) Given One Upfront the Other Upon Progression in Advanced Pancreatic Neuroendocrin Tumor (pNET) (SEQTOR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02246127
Recruitment Status : Active, not recruiting
First Posted : September 22, 2014
Last Update Posted : March 5, 2020
Sponsor:
Collaborators:
European Neuroendocrine Tumor Society
Kantar Health
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Grupo Espanol de Tumores Neuroendocrinos

Tracking Information
First Submitted Date  ICMJE August 20, 2014
First Posted Date  ICMJE September 22, 2014
Last Update Posted Date March 5, 2020
Actual Study Start Date  ICMJE October 27, 2014
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2020)
First Progression free survival [ Time Frame: At 12 months ]
Proportion of patients who are alive without progression to Course 1 from the date of randomization in STZ based CT vs Everolimus arms
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2014)
Second Progression Free Survival (second PFS) [ Time Frame: Up to 84 weeks ]
PFS of Course 1 (PFS1) + interval between treatments + PFS of Course 2 (PFS2), where PFS1 represents progression free survival of Course 1 and PFS2 represents progression free survival of Course 2
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2020)
  • Second Progression Free Survival (second PFS) [ Time Frame: Up to 140 +/- 8 weeks ]
    PFS of Course 1 (PFS1) + interval between treatments + PFS of Course 2 (PFS2), where PFS1 represents progression free survival of Course 1 and PFS2 represents progression free survival of Course 2
  • Hazard Ratio (HR) [ Time Frame: At 12 months and 140+/-8 weeks ]
    Second progression free survival (PFS of Course 1 + interval between treatments + PFS of course 2) as a continuous time variable.
  • Time to first progression [ Time Frame: Up to 44 weeks to everolimus and up 96 weeks for STZ-5-FU. ]
    Time from the date of randomization to the date of first disease progression.
  • Time to second progression [ Time Frame: Up to 140+/-8 weeks ]
    From the date of randomization to the date of second disease progression
  • Adverse events [ Time Frame: up to 30 days after 140 +/- 8 weeks ]
    Number of adverse events, dose reductions, and total dose administered of each treatment.
  • Ratio of incremental cost-efficacy (ICER) [ Time Frame: Up to 140+/-8 weeks ]
    Ratio of the difference of costs incurred on by each treatment arm and the difference of second progression free survival at each arm.
  • Response Rate (RR) [ Time Frame: Baseline and every 12 weeks up to 140+/-8 weeks ]
    Rate of objective response (= Complete response (CR)+ Partial Response (PR)+Stable Disease (SD)) measured by RECIST criteria version 1.0
  • Early Biochemical response [ Time Frame: Baseline and up to 4 weeks ]
    Levels of Chromogranin A (CgA)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2014)
  • Adverse events [ Time Frame: up to 30 days after 84 weeks ]
    Number of adverse events, dose reductions, and total dose administered of each treatment.
  • Time to first progression [ Time Frame: Up to 44 weeks to everolimus and up 40 weeks for STZ-5-FU. ]
    Time from the date of randomization to the date of first disease progression.
  • Ratio of incremental cost-efficacy (ICER) [ Time Frame: Up to 84 weeks. ]
    Ratio of the difference of costs incurred on by each treatment arm and the difference of second progression free survival at each arm.
  • Response Rate (RR) [ Time Frame: Baseline and every 12 weeks up to 84 weeks ]
    Rate of objective response (= Complete response (CR)+ Partial Response (PR)+Stable Disease (SD)) measured by RECIST criteria version 1.0
  • Early Biochemical response [ Time Frame: Baseline and up to 4 weeks ]
    Levels of Chromogranin A (CgA)
  • Time to second progression [ Time Frame: Up to 84 weeks. ]
    From the date of randomization to the date of second disease progression
Current Other Pre-specified Outcome Measures
 (submitted: March 3, 2020)
  • Overall survival (OS) [ Time Frame: Up to 140+/-8 weeks ]
    From the date of randomization until death from any cause.
  • Quality of Life Questionnaire (QLQ) [ Time Frame: Prior to initial dose on day 1 and after the last dose of each treatment ]
    QLQ-C30 ver 3.0 QLQ specific for gastrointestinal neuroendocrine tumors (GINET21)
Original Other Pre-specified Outcome Measures
 (submitted: September 18, 2014)
  • Quality of Life Questionnaire (QLQ) [ Time Frame: Prior to initial dose on day 1 and after the last dose of each treatment ]
    QLQ-C30 ver 3.0 QLQ specific for gastrointestinal neuroendocrine tumors (GINET21)
  • Overall survival (OS) [ Time Frame: Up to 84 weeks ]
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Everolimus and (STZ-5FU) Given One Upfront the Other Upon Progression in Advanced Pancreatic Neuroendocrin Tumor (pNET)
Official Title  ICMJE Randomized Open Label Study to Compare the Efficacy and Safety of Everolimus Followed by Chemotherapy With Streptozotocin- Fluorouracilo (STZ-5FU) Upon Progression or the Reverse Sequence, in Advanced Progressive Pancreatic NETs (pNETs)
Brief Summary The purpose of this study is to compare STZ vs everolimus as first line treatment for advanced pNET and to elucidate which sequence of streptozotocin (STZ) based chemotherapy and the mammalian Target of Rapamycin (mTOR) inhibitor, everolimus, gives better results in terms of second Progression Free Survival (PFS) in well differentiated and advanced pancreatic NETs.
Detailed Description

STZ based chemotherapy, STZ-5FU, is the actual standard of care for advanced pancreatic Neuroendocrine tumours (pNETS) in the European Union. Everolimus has been recently approved for its use in advanced pNETs by the Food and Drug Administration (FDA) and in Europe by the European Medical Agency (EMA).

A randomized study is needed to have a clear knowledge about the best sequence for its administration; this is, before or after palliative chemotherapy.

There may or may not be any benefits from giving first each other treatment of the study. The information obtained from this study will help the physician improve the treatment and management of patients with advanced pNET.

This study was planned to compare STZ-5FU chemotherapy followed by everolimus upon progression versus the reverse sequence. However sequential studies with pNETs are hard to be managed in terms of time and costs. Therefore the protocol was amended to have PFS1 (progression free survival after course 1) as primary endpoint and PFS2 (i.e. progression free survival after both STZ based chemotherapy and Everolimus or the reverse order) as secondary endpoint. This information will be extremely valuable for the day to day clinical practice of NET oncologists

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroendocrine Tumors
Intervention  ICMJE
  • Drug: Drug: Everolimus
    10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
    Other Name: Afinitor
  • Drug: STZ-5FU

    0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).

    Number of Cycles: until progression or unacceptable toxicity develops.

    Other Name: STZ based Chemotherapy
Study Arms  ICMJE
  • Active Comparator: Sequence A, drug: everolimus first
    Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
    Interventions:
    • Drug: Drug: Everolimus
    • Drug: STZ-5FU
  • Experimental: Sequence B, drug: STZ - 5FU first
    STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
    Interventions:
    • Drug: Drug: Everolimus
    • Drug: STZ-5FU
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 3, 2020)
141
Original Estimated Enrollment  ICMJE
 (submitted: September 18, 2014)
180
Estimated Study Completion Date  ICMJE July 2021
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically proven diagnosis of unresectable or metastatic, advanced pancreatic NET.
  • Documented confirmation of pancreatic NET G1 or G2 as per European Neuroendocrine Society (ENETS) classification system.
  • Patients from whom a paraffin-embedded primary tumour or metastasis block is available and to be sent by Courier.
  • Before study inclusion, patients must show progressive disease documented by radiology 12 months prior to study inclusion. Treatment naive patients can be also included if the patient needs active treatment with either chemotherapy or everolimus.
  • Presence of measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.0, documented by a Triphasic Computed Tomography (CT) scan or multiphase MRI radiological assessment.
  • Previous treatment with somatostatin (SS) analogues is allowed. Only those patients with active functioning syndrome at entry can continue with SS analogues during the study.
  • Adequate bone marrow and renal functions, and serum fasting cholesterol
  • Women with child-bearing potential must have a negative serum pregnancy test.
  • Written Informed Consent obtained according to local regulations

Exclusion Criteria:

  • Previous treatment with chemotherapy and/or mTOR inhibitors or tyrosine kinase inhibitors.
  • Immune therapy or radiation therapy within 4 weeks prior to the patient entering the study.
  • Hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation/radiofrequency ablation of hepatic metastasis within 2 months of enrolment.
  • Previous treatment with Peptide-Receptor Radionuclide Therapy (PRRT) within the last 6 months and/or without progression following PRRT.
  • Uncontrolled diabetes mellitus.
  • Any severe and/or uncontrolled medical conditions.
  • Treatment with potent inhibitors or inducers of Cytochrome P450 3A4 (CYP3A) isoenzyme within 5 days immediately before the start of treatment.
  • Patients on chronic treatment with corticosteroids or any other immunosuppressive agent.
  • Patients known to be HIV seropositive.
  • Known intolerance or hypersensitivity to everolimus or its excipients or other rapamycin analogues. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
  • Known intolerance or hypersensitivity to 5FU or STZ or its excipients (notice that this criterion includes patients with known deficit of dihydropyrimidine dehydrogenase deficiency -DPD).
  • Pregnant, lactating women or fertile adults not using effective birth control methods.
  • For administrative matters (insurance) patients ≥ 95 are not allowed during the trial.

Only those patients coming from the hospital pool will be included in SEQTOR trial (e.g. persons detained in an institution as a result of an official or court order are excluded).

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 94 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   France,   Germany,   Italy,   Netherlands,   Spain,   Sweden,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02246127
Other Study ID Numbers  ICMJE GETNE1206
2013-000726-66 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: As per GETNE guidelines and local laws
Responsible Party Grupo Espanol de Tumores Neuroendocrinos
Study Sponsor  ICMJE Grupo Espanol de Tumores Neuroendocrinos
Collaborators  ICMJE
  • European Neuroendocrine Tumor Society
  • Kantar Health
  • Novartis Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Salazar Ramon, MD, PhD Instituto Catalán de Oncologia, ICO-Hospitalet
PRS Account Grupo Espanol de Tumores Neuroendocrinos
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP