A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours
Conditions
Carcinoid Tumor of the Small Bowel - Neuroendocrine Tumour
Conditions: official terms
Apudoma - Carcinoid Tumor - Neoplasms - Neuroendocrine Tumors
Conditions: Keywords
Neuroendocrine tumour, 177Lu-Dota0-Tyr3-octreotate
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Octreotide LAR Type: Drug
Name: 177Lu-DOTA0-Tyr3-Octreotate Type: Drug
Overall Status
Recruiting
Summary
The purpose of this study is to

- compare Progression Free Survival (PFS) after treatment with 177Lu-DOTA0-Tyr3-Octreotate plus best supportive care (30 mg Octreotide LAR) to treatment with high dose (60 mg) Octreotide LAR in patients with inoperable, progressive (as determined by Response Evaluation Criteria in Solid Tumors [RECIST] Criteria), somatostatin receptor positive, well-differentiated neuroendocrine tumours of the small bowel (midgut carcinoid tumours).

- compare the Objective Response Rate (ORR) between the two study arms

- compare the Overall Survival (OS) between the two study arms

- compare the Time to Tumour Progression (TTP) between the two study arms

- evaluate the safety and tolerability of 177Lu-DOTA0-Tyr3-Octreotate

- evaluate the health related quality of life (QoL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-G.I.NET21 questionnaire

- explore the correlation of toxicity outcomes and administered radiation doses corrected for body weight and body surface area

- explore the correlation of clinical efficacy outcomes with the levels of the biomarkers Chromogranin-A (CgA) in the serum and 5-Hydroxyindoleacetic acid (5-HIAA) in the urine

- evaluate dosimetry, pharmacokinetics (PK) and ECG in a subset of 20 patients

- explore the correlation of clinical efficacy outcomes with OctreoScan® tumour uptake score

- explore the correlation of clinical outcomes with serum levels of Alkaline Phosphatase (AP)
Detailed Description
A multicenter, stratified, open, randomized, comparator-controlled, parallel-group phase III study. In this study, treatment with 177Lu-DOTA0-Tyr3-Octreotate plus best supportive care (30 mg Octreotide LAR) will be compared to treatment with high dose (60 mg) Octreotide LAR in patients with inoperable, somatostatin receptor positive, histologically proven midgut carcinoid tumours; these patients should be progressive under Octreotide LAR. In case patients in either arm experience clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections are allowed.

Objective tumour response in both arms will be assessed every 12±1 weeks from the first treatment date according to RECIST Criteria. The baseline CT scan/MRI must not be older than 4 weeks before the projected randomization date.

Patients will be evaluated for safety and tolerability in accordance with the Visit Schedules for the 177Lu-DOTA0-Tyr3-Octreotate arm and the Octreotide LAR arm as indicated in Table 1 and Table 2, respectively.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. Presence of metastasized or locally advanced, inoperable (curative intent) at enrollment time, histologically proven, midgut carcinoid tumour (to be centrally confirmed).

2. Ki67 index ≤ 20% (to be centrally confirmed).

3. Patients on Octreotide LAR at a fixed dose of 20 mg or 30 mg at 3-4 weeks intervals for at least 12 weeks prior to randomization in the study.

4. Patients ≥18 years of age.

5. Patients must have progressive disease based on RECIST Criteria, Version 1.1 while receiving an uninterrupted fixed dose of Octreotide LAR (20-30 mg/3-4 weeks). Disease progression must be centrally confirmed. In order to make the assessment, two CT (or MRI) scans are required. The oldest scan must not be older than 3 years from the date of randomization. The most recent scan must not be older than 4 weeks from the date of randomization. Both scans must be obtained while the patient is receiving the same fixed dose of Octreotide LAR (20-30 mg/3-4 weeks) with the following exceptions; 1) it is acceptable if the oldest scan is obtained within 12 weeks of the patient receiving a fixed dose regimen of Octreotide LAR (20-30 mg/3-4 weeks); AND 2) it is acceptable for either scan to be obtained before or during the time a patient receiving a fixed dose of Octreotide LAR has switched to an equivalent dose of short acting Octreotide for up to 6 weeks in order to obtain an OctreoScan®, provided the patient returns to the Octreotide LAR fixed dose after the OctreoScan® has been obtained.

6. Confirmed presence of somatostatin receptors on all target lesions (for target/non-target/measurable lesions definition see §Appendix 2, Section 1 and 2, RECIST Criteria, Version 1.1) documented by CT/MRI scans, based on positive OctreoScan® imaging within 24 weeks prior to randomization in the study (to be centrally confirmed). The OctreoScan® should be one that was performed while the patient was on a fixed dose of Octreotide LAR. If a patient has had an OctreoScan® performed while Octreotide LAR treatment-naïve, the patient must have a repeat OctreoScan® performed after 3 months of Octreotide LAR treatments before entering the clinical study to prove that the index lesions or new lesions still meet the criteria for inclusion. It is acceptable to have patients temporarily switched to Octreotide s.c. (up to six weeks) in order to obtain an OctreoScan®, provided they return to the same fixed dose of Octreotide LAR prior to the scan.

7. The tumour uptake observed in each target lesion (for target/non-target/measurable lesions definition see §Appendix 2, Sections 1 and 2, RECIST Criteria, Version 1.1) using OctreoScan® must be ≥ normal liver uptake observed on planar imaging (to be centrally confirmed) (§Appendices 5 and 6).

8. Karnofsky Performance Score (KPS)>=60.

9. Presence of at least 1 measurable site of disease.

10. [Applicable only for France] All patients included in the trial must be affiliated with a social security regime or be a beneficiary of the same in order to be included in the study.

Exclusion Criteria:

1. Either serum creatinine >150 µmol/L (>1.7 mg/dL), or creatinine clearance <50 mL/min calculated by the Cockroft Gault method, eventually confirmed by measured creatinine clearance (or measured glomerular filtration rate (GFR) using plasma clearance methods, not gamma camera-based) <50 mL/min (the measured creatinine clearance / GFR is required only as confirmatory exam).

2. Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L (2000/mm3); platelets <75x109/L (75x103/mm3).

3. Total bilirubin >3 x ULN.

4. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.

5. Pregnancy or lactation.

6. For female patients of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) and male patients, who are not surgically sterile or with female partners of childbearing potential: absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel) as defined in §Appendix 7.

7. Treatment with >30 mg Octreotide LAR at 3-4 weeks intervals within 12 weeks prior to randomization in the study.

8. Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the study.

9. Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency ablation within 12 weeks prior to randomization in the study.

10. Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks prior to randomization in the study.

11. Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrollment in the study. Patients with a history of brain metastases must have a head CT with contrast to document stable disease prior to randomization in the study.

12. Uncontrolled congestive heart failure (NYHA II, III, IV).

13. Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.

14. Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of 177Lu-DOTA0-Tyr3-Octreotate, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 6 weeks before the administration of 177Lu-DOTA0-Tyr3-Octreotate, unless the tumour uptake on target lesions observed by OctreoScan® imaging during continued Octreotide LAR treatment is at least as high as normal liver uptake observed by planar imaging.

15. Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.

16. Prior external beam radiation therapy to more than 25% of the bone marrow.

17. Current spontaneous urinary incontinence.

18. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.

19. Patients who have not provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related activities.

20. Patient with known incompatibility to CT Scans with I.V. contrast due to allergic reaction or renal insufficiency. If such a patient can be imaged with MRI, then the patient would not be excluded.

21. Patients who have participated in any therapeutic clinical study/received any investigational agent within the last 30 days are excluded from participation in this trial.
Locations
Cedars-Sinai Medical Center Samuel Oschin Cancer Center
Los Angeles, California, United States
Status: Recruiting
Contact: Andrew Hendifar, MD - 310-423-2217 - andrew.hendifar@cshs.org
Stanford University Medical Center
Stanford, California, United States
Status: Recruiting
Contact: Erik Mittra, MD, PhD - 650-721-2024 - emittra@stanford.edu
H Lee Moffitt Cancer Center
Tampa, Florida, United States
Status: Recruiting
Contact: Jonathan Strosberg, MD - 813-745-7257 - jonathan.strosberg@moffitt.org
Robert H. Lurie Comprehensive Cancer Center, Northwestern Univ.
Chicago, Illinois, United States
Status: Recruiting
Contact: Al B Benson, MD - 312-695-0990 - a-benson@northwestern.edu
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Status: Recruiting
Contact: David Bushnell, MD - 319-338-0581 - david-bushnell@uiowa.edu
Oshsner Medical Center
Kenner, Louisiana, United States
Status: Withdrawn
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Status: Recruiting
Contact: Matthew H Kulke, MD - 617-632-5138 - matthew_kulke@dfci.harvard.edu
Mayo Clinic
Rochester, Minnesota, United States
Status: Recruiting
Contact: Timothy Hobday, MD - 507-284-2511 - hobday.timothy@mayo.edu
Weill-Cornell Medical College / New York Prebyterian
New York City, New York, United States
Status: Withdrawn
Duke University Medical Center
Durham, North Carolina, United States
Status: Recruiting
Contact: Michael Morse, MD - 919-681-3480 - michael.morse@duke.edu
Kettering Medical Center
Kettering, Ohio, United States
Status: Recruiting
Contact: Meike L Schipper, MD - 937-395-8611 - meike.schipper@khnetwork.org
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Status: Recruiting
Contact: David Metz, MD - 215-662-4279 - david.metz@uphs.upenn.edu
Vanderbilt University - Ingram Cancer Center
Nashville, Tennessee, United States
Status: Recruiting
Contact: Jordan Berlin, MD - 615-373-4967 - Jordan.berlin@vanderbilt.edu
Excel Diagnostics and Nuclear Oncology Center
Houston, Texas, United States
Status: Recruiting
Contact: Ebrahim Delpassand, MD - 713-781-6200 - edelpassand@exceldiagnostics.com
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Status: Recruiting
Contact: James Yao, MD - 713-792-2828 - jyao@mdanderson.org
Allgemeines Krankenhaus , Universitatsklinik fur Nuclearmedizin
Wien, Austria
Status: Not yet recruiting
Contact: Martha Hoffmann, MD - 0043-1-40400-5550 - martha.hoffmann@meduniwien.ac.at
Wilhelminenspital
Wien, Austria
Status: Not yet recruiting
Contact: Siroos Mirzaei, MD - 0043-1-49150 - siroos.mirzaei@wienkav.at
Digestive Oncology, Leuven Cancer Institute
Leuven, Brabant flamand, Belgium
Status: Recruiting
Contact: Eric Van Cutsem, Pr. - 0032 16 34 42 18 - Eric.VanCutsem@uzleuven.be
Hôpital Beaujon AP-HP
Paris, Ile de France, France
Status: Recruiting
Contact: Philippe Ruszniewski, Pr. - 0033 1 40 87 53 28 - philippe.ruszniewski@bjn.aphp.fr
Institut Gustave Roussy
Villejuif Cedex, Ile de France, France
Status: Recruiting
Contact: Eric Baudin, Ass. Pr. - 0033 1 42 11 42 11 - Eric.baudin@igr.fr
Institut Claudius Regaud
Toulouse, Midi-Pyrénées, France
Status: Recruiting
Contact: Frederic Courbon, Pr. Dr. - 0033 5 67 69 63 20 - Courbon.Frederic@claudiusregaud.fr
Hotel Dieu/CHU Nantes
Nantes, Pays de la Loire, France
Status: Recruiting
Contact: Catherine Ansquer, Dr. - 0033 2 40 08 41 36 - catherine.ansquer@chu-nantes.fr
Hôpital la Timone /CHU Marseille
Marseille, Provence-Alpes-Côte d'Azur, France
Status: Recruiting
Contact: David Taieb, Ass. Pr. - 0033 4 91 38 55 58 - David.TAIEB@ap-hm.fr
Groupement Hospitalier Est
Lyon, Rhône-Alpes, France
Status: Recruiting
Contact: Francesco Gianmarile, Dr. - 0033 4 78 86 21 76 - francesco.giammarile@chu-lyon.fr
Universitätsklinikum Tübingen, Medizinische Universitätsklinik,
Tubingen, Baden-Württemberg, Germany
Status: Withdrawn
Klinikum Rechts Isar, Nuclear Medicine
Munich, Bayern, Germany
Status: Recruiting
Contact: Klemens Scheidhauer, Pr. Dr. - 0049 (0)89 4140-2960 - k.scheidhauer@lrz.tum.de
Universitätsklinikum Bonn, Klinik und Poliklinik für Nuklearmedizin
Bonn, Nordrhein-Westfalen, Germany
Status: Withdrawn
Universitätsmedizin Mainz, Medizinische Klinik I Schwerpunkt Endokrinologie
Mainz, Rheinland-Pfalz, Germany
Status: Recruiting
Contact: Matthias Weber, Pr. Dr. - 0049 (0) 6131 177260 - weber@endokrinologie.klinik.uni-mainz.de
Zentralklinik Bad Berka
Bad Berka, Thüringen, Germany
Status: Recruiting
Contact: Richard Baum, Pr. Dr - 0049 (0) 364 58 52200 - richard.baum@zentralklinik.de
Charité, Virchow-Klinikum, Gastroentrology, Hepatology & Endocrinology
Berlin, Germany
Status: Recruiting
Contact: Bertram Wiedenmann, Pr. Dr. - 0049 (0)30 450 553022 - bertram.wiedenmann@charite.de
Ospedale Oncologico Regionale
Rionero in Vulture, Basilicata, Italy
Status: Withdrawn
Federico II University/Fondazione G. Pascale
Naples, Campania, Italy
Status: Withdrawn
Istituto Oncologico Romagnolo per lo Studio dei Tumori
Meldola, Emilia-Romagna, Italy
Status: Recruiting
Contact: Stefano Severi, Dr. - 0039 0543.739318 - s.severi@irst.emr.it
IEO Istituto Europeo di Oncologia
Milano, Lombardia, Italy
Status: Recruiting
Contact: Giovanni Paganelli, Dr. - 0039 02.57489044 - giovanni.paganelli@ieo.it
Presidio Osp. Di Macerata
Macerata, Marche, Italy
Status: Recruiting
Contact: Ernesto Brianzoni, Dr. - 0039 0733.2572941 - ernesto.brianzoni@sanita.marche.it
Azienda Ospedaliero - Universitaria Pisana (Presidio Ospedaliero S. Chiara)
Pisa, Toscana, Italy
Status: Recruiting
Contact: Giuliano Mariani, Dr. - 0039 050 993390 - g.mariani@do.med.unipi.it
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, Italy
Status: Recruiting
Contact: Ettore Seregni, MD - 0039 02 23902635 - ettore.seregni@istitutotumori.mi.it
Istituto Nazionale Tumori - IRCCS - Fondazione Pascale
Naples, Italy
Status: Withdrawn
Università "Sapienza" di Roma, Facoltà di Medicina e Psicologia, Ospedale S. Andrea-Roma
Roma, Italy
Status: Recruiting
Contact: Gianfranco Delle Fave, MD - 0039 0633775691 - "gianfranco.dellefave@gmail.com
Hospitais da Universidade de Coimbra
Coimbra, Centro, Portugal
Status: Terminated
Instituto Português de Oncologia
Porto, Norte, Portugal
Status: Recruiting
Contact: Isabel Azevedo, Dr. - 00 351 22 5084000 - isabelazv@gmail.com
University Hospital of Bellvitge
Hospitalet de Llobregat (Barcelona), Cataluña, Spain
Status: Recruiting
Contact: Jaime Mora, Dr. - 00 34 93 2607620 - jmoras@bellvitgehospital.cat
Ramon y Cajal University Hospital
Madrid, Spain
Status: Recruiting
Contact: Enrique Grande, Dr. - 00 34 91 3368000 - egrande@oncologiahrc.com
Hospital universitario La Fe
Valencia, Spain
Status: Recruiting
Contact: Pilar Bello, MD - bello_pil@gva.es
University of Oxford
Oxford, South East England, United Kingdom
Status: Recruiting
Contact: Ashley Grossman, Dr. - 0044 01865859129 - ashley.grossman@ocdem.ox.ac.uk
Queen Elizabeth Hospital @ Birmingham
Birmingham, United Kingdom
Status: Withdrawn
Beatson Oncology Centre
Glasgow, United Kingdom
Status: Recruiting
Contact: Nicholas Reed, Dr. - 00 44 141 301 7057 - nick.reed@ggc.scot.nhs.uk
"Nuclear Medicine Consultant
Liverpool, United Kingdom
Status: Recruiting
Contact: Sobhan Vinjamuri - +44 (0)151 706 4462 - Sobhan.Vinjamuri@rlbuht.nhs.uk
"Institute for Liver Studies
London, United Kingdom
Status: Recruiting
Contact: Raj Srirajaskanthan, MD - r.srirajaskanthan@nhs.net
Imperial College Healthcare Trust, Hammersmith Hospital
London, United Kingdom
Status: Recruiting
Contact: Adil AL-Nahhas, Pr. - 0044 20 7535 5544 - Adil.Al-Nahhas@imperial.nhs.uk
Royal Free Hospital
London, United Kingdom
Status: Recruiting
Contact: Martyn Caplin, Dr. - 0044 20 7830 2867 - m.caplin@ucl.ac.uk
The Christie NHS foundation Trust
Manchester, United Kingdom
Status: Recruiting
Contact: Prakash Manoharan, MD - 0044 161 446 8246 - "Prakash.Manoharan@christie.nhs.uk
Start Date
September 2012
Completion Date
December 2019
Sponsors
Advanced Accelerator Applications
Source
Advanced Accelerator Applications
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page