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

NCT01648465 | Terminated Phase 2

• 2 other identifiers: HE 67/122011-006160-48
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 12

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.

Conditions

Gastrointestinal Tumors; Pancreatic Tumors; Gastrointestinal Neuroendocrine Tumors; Pancreatic Neuroendocrine Tumors

Keywords

metastatic; unresectable; well or moderately differentiated; advanced

Outcome Measures

Primary Outcomes (1)

• 15 month PFS (Progression-Free Survival) rate

  To determine the rate of PFS patients at 15 months of treatment.

  15 months

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  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.

• Overall Survival (OS)

  Defined as the time from the date of enrollment to the date of death from any cause,assessed up to 36 months.

• Evaluation of best response to treatment and the time to best response achievement

  Defined as the period from the date of treatment initiation to best response observation date througout the study, assessed up to 15 months.

• Assessment of safety

  Assessment of adverse events will be performed every 28 days (per cycle) during treatment, assessed up to 16 months.

• Association of biologic markers with disease progression

  Up to 36 months

Study Arms (1)

Everolimus

EXPERIMENTAL

Drug: Everolimus

Interventions

Everolimus DRUG

Everolimus 10mg(2x5mg)orally once daily until disease progression, unacceptable toxicity or consent withdrawal

Also known as: Afinitor, RAD001

Everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged ≥ 18 years of age.
• Newly diagnosed patients with biopsy-proven well or moderately differentiated advanced (metastatic or unresectable) GI or pancreatic neuroendocrine tumor.
• Measurable disease based on RΕCIST 1.1 using a triphase CT scan or multi-phase MRI scan.
• Patients with a ki-67 measurement \<20% prior to their enrollment to the study.
• Performance status 0-2 on the WHO scale.
• Adequate bone marrow function as shown by:ANC ≥ 1.5 x 10\^9/L,Platelets ≥ 100 x 10\^9/L,Hemoglobin \> 9 g/dL.
• 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).
• Adequate renal function as shown by: serum creatinine ≤ 1.5 x ULN.
• 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.
• Women of childbearing potential, with a negative serum or urine pregnancy test within 48 hours prior to first study treatment administration.
• Signed informed consent form obtained before any trial related activity, including the screening phase, according to the applicable law and ICH/GCP requirements.
• Signed informed consent for the use of biological and genetic material

You may not qualify if:

• Patients with poorly differentiated or undifferentiated GI or pancreatic neuroendocrine carcinoma.
• Previous or concurrent cytotoxic chemotherapy, immunotherapy or radiotherapy.
• Hepatic artery embolization or cryoablation of hepatic metastasis within 1 month of study enrollment.
• Prior therapy with mTOR inhibitors (for example sirolimus, temsirolimus, everolimus).
• Patients receiving chronic treatment with corticosteroid immunosuppressives.
• Uncontrolled diabetes mellitus as defined by fasting serum glucose \> 1.5 x ULN.
• 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).
• Active bleeding diathesis or on oral treatment with vitamin K antagonists (apart from low-dose coumadine).
• Performance status ≥ 3 on the WHO scale.
• Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead
• Novartis: collaborator

Study Sites (12)

2nd Dept of Internal Medicine, Agios Savvas Cancer Hospital

Athens, 11522, Greece

Location

Dept of Medical Oncology, 251 General Airforce Hospital

Athens, 11525, Greece

Location

2nd Dept of Internal Medicine, General Hospital of Athens "Hippokratio"

Athens, 11527, Greece

Location

2nd Dept of Internal Medicine, Propaedeutic, University Hospital "Attikon"

Athens, 12462, Greece

Location

4th Dept of Internal Medicine, University Hospital "Attiko"

Athens, 12462, Greece

Location

3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

Athens, 14564, Greece

Location

2nd Dept of Medical Oncology, Metropolitan Hospital

Athens, 18547, Greece

Location

Dept of Medical Oncology, University Hospital of Heraklion

Heraklion, 71110, Greece

Location

Dept of Medical Oncology, Ioannina University Hospital

Ioannina, 45110, Greece

Location

Division of Oncology, Dept of Internal Medicine, University Hospital of Patras

Pátrai, 26504, Greece

Location

Dept of Medical Oncology, Papageorgiou General Hospital

Thessaloniki, 56429, Greece

Location

Dept of Medical Oncology, Thermi Clinic

Thessaloniki, 57001, Greece

Location

Related Publications (1)

• Koumarianou A, Pectasides D, Koliou GA, Dionysopoulos D, Kolomodi D, Poulios C, Skondra M, Sgouros J, Pentheroudakis G, Kaltsas G, Fountzilas G. Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study. Biology (Basel). 2020 Mar 9;9(3):51. doi: 10.3390/biology9030051.

  PMID: 32182791 DERIVED

MeSH Terms

Conditions

Digestive System Neoplasms; Pancreatic Neoplasms; Neoplasm Metastasis

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Anna Koumarianou, Dr

  4th Dept of Internal Medicine, University Hospital "Attikon"

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2012
• First Posted: July 24, 2012
• Study Start: August 6, 2012
• Primary Completion: January 1, 2017
• Study Completion: August 6, 2019
• Last Updated: September 3, 2019

Record last verified: 2019-08

Locations

GR (12)