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

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. Identifier: NCT01648465
Recruitment Status : Terminated
First Posted : July 24, 2012
Last Update Posted : September 3, 2019
Information provided by (Responsible Party):
Hellenic Cooperative Oncology Group

Brief Summary:
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 or disease Intervention/treatment Phase
Gastrointestinal Tumors Pancreatic Tumors Gastrointestinal Neuroendocrine Tumors Pancreatic Neuroendocrine Tumors Drug: Everolimus Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (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.
Actual Study Start Date : August 6, 2012
Actual Primary Completion Date : January 2017
Actual Study Completion Date : August 6, 2019

Arm Intervention/treatment
Experimental: Everolimus Drug: Everolimus
Everolimus 10mg(2x5mg)orally once daily until disease progression, unacceptable toxicity or consent withdrawal
Other Names:
  • Afinitor
  • RAD001

Primary Outcome Measures :
  1. 15 month PFS (Progression-Free Survival) rate [ Time Frame: 15 months ]
    To determine the rate of PFS patients at 15 months of treatment.

Secondary Outcome Measures :
  1. 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. ]
  2. 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. ]
  3. 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. ]
  4. Assessment of safety [ Time Frame: Assessment of adverse events will be performed every 28 days (per cycle) during treatment, assessed up to 16 months. ]
  5. Association of biologic markers with disease progression [ Time Frame: Up to 36 months ]

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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 <20% 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.
  12. Signed informed consent for the use of biological and genetic material

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.

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 identifier (NCT number): NCT01648465

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2nd Dept of Internal Medicine, Agios Savvas Cancer Hospital
Athens, Greece, 11522
Dept of Medical Oncology, 251 General Airforce Hospital
Athens, Greece, 11525
2nd Dept of Internal Medicine, General Hospital of Athens "Hippokratio"
Athens, Greece, 11527
2nd Dept of Internal Medicine, Propaedeutic, University Hospital "Attikon"
Athens, Greece, 12462
4th Dept of Internal Medicine, University Hospital "Attiko"
Athens, Greece, 12462
3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital
Athens, Greece, 14564
2nd Dept of Medical Oncology, Metropolitan Hospital
Athens, Greece, 18547
Dept of Medical Oncology, University Hospital of Heraklion
Heraklion, Greece, 71110
Dept of Medical Oncology, Ioannina University Hospital
Ioannina, Greece, 45110
Division of Oncology, Dept of Internal Medicine, University Hospital of Patras
Patra, Greece, 26504
Dept of Medical Oncology, Papageorgiou General Hospital
Thessaloniki, Greece, 56429
Dept of Medical Oncology, Thermi Clinic
Thessaloniki, Greece, 57001
Sponsors and Collaborators
Hellenic Cooperative Oncology Group
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Study Chair: Anna Koumarianou, Dr 4th Dept of Internal Medicine, University Hospital "Attikon"

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Responsible Party: Hellenic Cooperative Oncology Group Identifier: NCT01648465    
Other Study ID Numbers: HE 67/12
2011-006160-48 ( EudraCT Number )
First Posted: July 24, 2012    Key Record Dates
Last Update Posted: September 3, 2019
Last Verified: August 2019
Keywords provided by Hellenic Cooperative Oncology Group:
well or moderately differentiated
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Pancreatic Neoplasms
Digestive System Neoplasms
Gastrointestinal Neoplasms
Intestinal Neoplasms
Stomach Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Stomach Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents