ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    seqtor
Previous Study | Return to List | Next Study

Efficacy and Safety of Everolimus and (STZ-5FU) Given One Upfront the Other Upon Progression in Advanced 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02246127
Recruitment Status : Recruiting
First Posted : September 22, 2014
Last Update Posted : May 31, 2017
Sponsor:
Collaborators:
European Neuroendocrine Tumor Society
Kantar Health
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Grupo Espanol de Tumores Neuroendocrinos

Brief Summary:
The purpose of this study is 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.

Condition or disease Intervention/treatment Phase
Neuroendocrine Tumors Drug: Drug: Everolimus Drug: STZ-5FU Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : October 27, 2014
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Active Comparator: Sequence A, drug: everolimus first
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
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

Experimental: Sequence B, drug: STZ - 5FU first
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Early Biochemical response [ Time Frame: Baseline and up to 4 weeks ]
    Levels of Chromogranin A (CgA)

  6. Time to second progression [ Time Frame: Up to 140+/-8 weeks ]
    From the date of randomization to the date of second disease progression


Other Outcome Measures:
  1. 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)

  2. Overall survival (OS) [ Time Frame: Up to 140+/-8 weeks ]
    From the date of randomization until death from any cause.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 94 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02246127


Contacts
Contact: Cristina Vidal, BSc, PhD +34932134478 cvidal@needsamdaims.com
Contact: Valentin Navarro, BStatistics :+34 93 260 78 22 vnavarro@iconcologia.net

  Show 36 Study Locations
Sponsors and Collaborators
Grupo Espanol de Tumores Neuroendocrinos
European Neuroendocrine Tumor Society
Kantar Health
Novartis Pharmaceuticals
Investigators
Principal Investigator: Salazar Ramon, MD, PhD Instituto Catalán de Oncologia, ICO-Hospitalet

Responsible Party: Grupo Espanol de Tumores Neuroendocrinos
ClinicalTrials.gov Identifier: NCT02246127     History of Changes
Other Study ID Numbers: GETNE1206
2013-000726-66 ( EudraCT Number )
First Posted: September 22, 2014    Key Record Dates
Last Update Posted: May 31, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: As per GETNE guidelines and local laws

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Grupo Espanol de Tumores Neuroendocrinos:
advanced pNET
everolimus
STZ-5FU
treatment sequence

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Everolimus
Sirolimus
Fluorouracil
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic