Study of Everolimus Treatment in Newly-diagnosed Patients With Advanced Gastrointestinal Neuroendocrine Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Hellenic Cooperative Oncology Group
Sponsor:
Collaborator:
Novartis Hellas
Information provided by (Responsible Party):
Hellenic Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT01648465
First received: July 13, 2012
Last updated: October 22, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to explore the efficacy and safety of everolimus administered as a first-line treatment in newly-diagnosed patients with advanced or inoperable Gastrointestinal (GI) or pancreatic neuroendocrine tumors.


Condition Intervention Phase
Gastrointestinal Tumors
Pancreatic Tumors
Gastrointestinal Neuroendocrine Tumors
Pancreatic Neuroendocrine Tumors
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Multicenter Single-arm Study Evaluating the Safety and Efficacy of Everolimus as a First-line Treatment in Newly-diagnosed Patients With Advanced GI Neuroendocrine Tumors.

Resource links provided by NLM:


Further study details as provided by Hellenic Cooperative Oncology Group:

Primary Outcome Measures:
  • 15 month PFS (Progression-Free Survival) rate [ Time Frame: 15 months ] [ Designated as safety issue: No ]
    To determine the rate of PFS patients at 15 months of treatment.


Secondary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Defined as the time from the date of enrollment to the date of 1st radiologically documented disease progression or disease related death,assessed up to 36 months. ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Defined as the time from the date of enrollment to the date of death from any cause,assessed up to 36 months. ] [ Designated as safety issue: No ]
  • Evaluation of best response to treatment and the time to best response achievement [ Time Frame: Defined as the period from the date of treatment initiation to best response observation date througout the study, assessed up to 15 months. ] [ Designated as safety issue: No ]
  • Assessment of safety [ Time Frame: Assessment of adverse events will be performed every 28 days (per cycle) during treatment, assessed up to 16 months. ] [ Designated as safety issue: Yes ]
  • Association of biologic markers with disease progression [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 29
Study Start Date: July 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus Drug: Everolimus
Everolimus 10mg(2x5mg)orally once daily until disease progression, unacceptable toxicity, consent withdrawal or completion of 15 months of treatment
Other Names:
  • Afinitor
  • RAD001

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, aged ≥ 18 years of age.
  2. Newly diagnosed patients with biopsy-proven well or moderately differentiated advanced (metastatic or unresectable) GI or pancreatic neuroendocrine tumor.
  3. Measurable disease based on RΕCIST 1.1 using a triphase CT scan or multi-phase MRI scan.
  4. Patients with a ki-67 measurement prior to their enrollment to the study.
  5. Performance status 0-2 on the WHO scale.
  6. Adequate bone marrow function as shown by:ANC ≥ 1.5 x 10^9/L,Platelets ≥ 100 x 10^9/L,Hemoglobin > 9 g/dL.
  7. Adequate liver function as shown by:Serum bilirubin ≤ 1.5 x ULN,ALT/SGPT and AST/SGOT ≤ 2.5 x ULN (ή ≤ 5 x ULN in patients with known liver metastases),INR < 1.3 (INR < 3 in patients treated with anticoagulants).
  8. Adequate renal function as shown by: serum creatinine ≤ 1.5 x ULN.
  9. Fasting serum cholesterol ≤ 300 mg/dL or ≤ 7.75 mmol/L and fasting triglycerides ≤ 2.5 x ULN. Note: In case one or both the above upper limits are exceeded, patient enrollment can only be performed upon proper antilipidemic treatment initiation.
  10. Women of childbearing potential, with a negative serum or urine pregnancy test within 48 hours prior to first study treatment administration.
  11. Signed informed consent form obtained before any trial related activity, including the screening phase, according to the applicable law and ICH/GCP requirements.

Exclusion Criteria:

  1. Patients with poorly differentiated or undifferentiated GI or pancreatic neuroendocrine carcinoma.
  2. Previous or concurrent cytotoxic chemotherapy, immunotherapy or radiotherapy.
  3. Hepatic artery embolization or cryoablation of hepatic metastasis within 1 month of study enrollment.
  4. Prior therapy with mTOR inhibitors (for example sirolimus, temsirolimus, everolimus).
  5. Patients receiving chronic treatment with corticosteroid immunosuppressives.
  6. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN.
  7. Patients who have any severe and/or uncontrolled medical conditions such as:

    • unstable angina pectoris, symptomatic congestive heart failure NYHA class II, III, IV, myocardial infarction ≤ 6 months prior to enrollment, serious uncontrolled cardiac arrhythmia (LVEF < 50 %)
    • active or uncontrolled severe infection
    • cirrhosis, chronic active hepatitis, chronic persistent hepatitis or inadequate hepatic function (ALT/SGPT and AST/SGOT > 5 x ULN)
    • inadequate bone marrow (ANC < 1.5 x 10^9/L, platelets < 100 x 10^9/L, hemoglobin ≤ 9 g/dL) or renal failure (serum creatinine > 1.5 x ULN
    • severely impaired lung function (patients needing oxygen support).
  8. Active bleeding diathesis or on oral treatment with vitamin K antagonists (apart from low-dose coumadine).
  9. Performance status ≥ 3 on the WHO scale.
  10. Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
  11. No other prior or concurrent malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or treated in situ cancer of the cervix, or any other cancer from which the patient has been disease free for ≥ 3 years.
  12. Patients within 28 days post-major surgery (e.g. intra-thoracic, intrabdominal or intra-pelvic), open biopsy, or significant traumatic injury to avoid wound healing complications. Minor procedures and percutaneous biopsies or placement of vascular access device require 7 days prior to study entry. Note: Patients must have recovered from the acute effects of surgery prior to enrollment.
  13. Female patients who are pregnant or nursing (lactating).
  14. Adults with reproductive potential who are not using effective birth control methods. If barrier contraceptive measures are being used, these must be continued throughout the study by both sexes.
  15. Patients participating in another clinical trial or receiving an investigational drug.
  16. Patients unwilling or unable to comply with the protocol at the investigator's discretion.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01648465

Contacts
Contact: Anna Koumarianou, Dr 0030 210 5831675 akoumari@yahoo.com

Locations
Greece
2nd Dept of Internal Medicine, Propaedeutic, University Hospital "Attikon" Recruiting
Athens, Greece, 12462
Contact: Anna Koumarianou, Dr       akoumari@yahoo.com   
Principal Investigator: Anna Koumarianou, MD         
2nd Dept of Internal Medicine, General Hospital of Athens "Hippokratio" Recruiting
Athens, Greece, 11527
Contact: Dimitrios Pectasides, Professor       pectasid@otenet.gr   
Principal Investigator: Dimitrios Pectasides, Professor         
2nd Dept of Medical Oncology, Metropolitan Hospital Recruiting
Athens, Greece, 18547
Contact: Dimosthenis V. Skarlos, MD       hecogiat@otenet.gr   
Principal Investigator: Dimosthenis V. Skarlos, MD         
3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital Recruiting
Athens, Greece, 14564
Contact: Joseph Sgouros, Dr       josephsgouros@yahoo.co.uk   
Principal Investigator: Joseph Sgouros, MD         
Dept of Medical Oncology, University Hospital of Heraklion Recruiting
Heraklio, Greece, 71110
Contact: Vassilios Georgoulias, Professor       georgoul@med.uoc   
Principal Investigator: Vassilios Georgoulias, Professor         
Dept of Medical Oncology, Ioannina University Hospital Recruiting
Ioannina, Greece, 45110
Contact: George Penthroudakis, Ass.Professor       gpenther@otenet.gr   
Principal Investigator: George Pentheroudakis, Ass. Professor         
Division of Oncology, Dept of Internal Medicine, University Hospital of Patras Recruiting
Rio, Patras, Greece, 26504
Contact: Thomas Makatsoris, Dr       maktom@yahoo.com   
Principal Investigator: Thomas Makatsoris, MD         
Dept of Medical Oncology, Papageorgiou General Hospital Recruiting
Thessaloniki, Greece, 56429
Contact: George Fountzilas, Professor       fountzil@auth.gr   
Principal Investigator: George Fountzilas, Professor         
Sponsors and Collaborators
Hellenic Cooperative Oncology Group
Novartis Hellas
Investigators
Study Chair: Anna Koumarianou, Dr University Hospital "Attikon"
  More Information

No publications provided

Responsible Party: Hellenic Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT01648465     History of Changes
Other Study ID Numbers: HE 67/12, 2011-006160-48
Study First Received: July 13, 2012
Last Updated: October 22, 2013
Health Authority: Greece: Ethics Committee
Greece: National Organization of Medicines

Keywords provided by Hellenic Cooperative Oncology Group:
metastatic
unresectable
well or moderately differentiated
advanced

Additional relevant MeSH terms:
Digestive System Neoplasms
Gastrointestinal Neoplasms
Pancreatic Neoplasms
Neuroendocrine Tumors
Adenoma, Islet Cell
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Adenoma
Neoplasms, Glandular and Epithelial
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 22, 2014