A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours
This trial is active, not recruiting.
|Conditions||carcinoid tumor of the small bowel, neuroendocrine tumour|
|Treatments||octreotide lar, 177lu-dota0-tyr3-octreotate|
|Sponsor||Advanced Accelerator Applications|
|Collaborator||Pierrel Research Europe GmbH|
|Start date||September 2012|
|End date||July 2015|
|Trial size||230 participants|
|Trial identifier||NCT01578239, 2011-005049-11, AAA-III-01|
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)
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Los Angeles, CA||Cedars-Sinai Medical Center Samuel Oschin Cancer Center||no longer recruiting|
|Palo Alto, CA||Stanford Cancer Institute||no longer recruiting|
|Stanford, CA||Stanford University Medical Center||no longer recruiting|
|Tampa, FL||Moffitt Cancer Center||no longer recruiting|
|Chicago, IL||Northwestern University||no longer recruiting|
|Iowa City, IA||University of Iowa / Holden Comprehensive Cancer Center||no longer recruiting|
|Boston, MA||Dana-Farber Cancer Institute||no longer recruiting|
|Boston, MA||Dana Farber Cancer Institute||no longer recruiting|
|Rochester, MN||Mayo Clinic||no longer recruiting|
|Durham, NC||Duke University Medical Center||no longer recruiting|
|Durham, NC||Duke University Medical Center||no longer recruiting|
|Kettering, OH||Kettering Medical Center||no longer recruiting|
|Philadelphia, PA||University of Pennsylvania||no longer recruiting|
|Nashville, TN||Vanderbilt University / Ingram Cancer Center||no longer recruiting|
|Houston, TX||M D Anderson Cancer Center||no longer recruiting|
|Houston, TX||Excel Diagnostics and Nuclear Oncology Center||no longer recruiting|
|Wien, Austria||Allgemeines Krankenhaus , Universitatsklinik fur Nuclearmedizin||no longer recruiting|
|Wien, Austria||Wilhelminenspital||no longer recruiting|
|Leuven, Belgium||Digestive Oncology, Leuven Cancer Institute||no longer recruiting|
|Paris, France||Hôpital Beaujon AP-HP||no longer recruiting|
|Villejuif Cedex, France||Institut Gustave Roussy||no longer recruiting|
|Toulouse, France||Institut Claudius Regaud||no longer recruiting|
|Nantes, France||Hotel Dieu/CHU Nantes||no longer recruiting|
|Marseille, France||Hôpital la Timone /CHU Marseille||no longer recruiting|
|Lyon, France||Groupement Hospitalier Est||no longer recruiting|
|Berlin, Germany||Charité, Virchow-Klinikum, Gastroentrology, Hepatology & Endocrinology||no longer recruiting|
|Munich, Germany||Klinikum Rechts Isar, Nuclear Medicine||no longer recruiting|
|Mainz, Germany||Universitätsmedizin Mainz, Medizinische Klinik I Schwerpunkt Endokrinologie||no longer recruiting|
|Bad Berka, Germany||Zentralklinik Bad Berka||no longer recruiting|
|Milano, Italy||Fondazione IRCCS Istituto Nazionale dei Tumori||no longer recruiting|
|Roma, Italy||Università "Sapienza" di Roma, Facoltà di Medicina e Psicologia, Ospedale S. Andrea-Roma||no longer recruiting|
|Meldola, Italy||Istituto Oncologico Romagnolo per lo Studio dei Tumori||no longer recruiting|
|Milano, Italy||IEO Istituto Europeo di Oncologia||no longer recruiting|
|Macerata, Italy||Presidio Osp. Di Macerata||no longer recruiting|
|Pisa, Italy||Azienda Ospedaliero - Universitaria Pisana (Presidio Ospedaliero S. Chiara)||no longer recruiting|
|Coimbra, Portugal||Hospitais da Universidade de Coimbra||no longer recruiting|
|Porto, Portugal||Instituto Português de Oncologia||no longer recruiting|
|Madrid, Spain||Ramon y Cajal University Hospital||no longer recruiting|
|Valencia, Spain||Hospital universitario La Fe||no longer recruiting|
|Hospitalet de Llobregat (Barcelona), Spain||University Hospital of Bellvitge||no longer recruiting|
|Glasgow, United Kingdom||Beatson Oncology Centre||no longer recruiting|
|Liverpool, United Kingdom||"Nuclear Medicine Consultant||no longer recruiting|
|London, United Kingdom||Royal Free Hospital||no longer recruiting|
|London, United Kingdom||"Institute for Liver Studies||no longer recruiting|
|London, United Kingdom||Imperial College Healthcare Trust, Hammersmith Hospital||no longer recruiting|
|Manchester, United Kingdom||The Christie NHS foundation Trust||no longer recruiting|
|Oxford, United Kingdom||University of Oxford||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||parallel assignment|
Progression Free survival (PFS)
time frame: 12+/- 1 weeks
Safety assessments (Adverse Events, laboratory parameters, cancer related symptoms, Physical Examination, Vital signs, Karnofsky Performance Status, ECG)
time frame: 72 weeks (unless early termination) : All adverse events (AEs) and serious adverse events (SAEs) will be recorded starting from the signing of the informed consent until the last study-related visit in both study arms.
Long-term safety and efficacy assessment
time frame: Every 6 months for a period of up to 5 years after the end of the study
Male or female participants at least 18 years old.
- Presence of metastasized or locally advanced, inoperable (curative intent) at enrollment time, histologically proven, midgut carcinoid tumour (to be centrally confirmed).
- Ki67 index ≤ 20% (to be centrally confirmed).
- 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.
- Patients ≥18 years of age.
- 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.
- 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.
- 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).
- Karnofsky Performance Score (KPS)>=60.
- Presence of at least 1 measurable site of disease.
- [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.
- 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).
- Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L (2000/mm3); platelets <75x109/L (75x103/mm3).
- Total bilirubin >3 x ULN.
- Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
- Pregnancy or lactation.
- 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.
- Treatment with >30 mg Octreotide LAR at 3-4 weeks intervals within 12 weeks prior to randomization in the study.
- Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the study.
- Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency ablation within 12 weeks prior to randomization in the study.
- Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks prior to randomization in the study.
- 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.
- Uncontrolled congestive heart failure (NYHA II, III, IV).
- Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.
- 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.
- Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
- Prior external beam radiation therapy to more than 25% of the bone marrow.
- Current spontaneous urinary incontinence.
- 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.
- 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.
- 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.
- 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.
|Official title||A Multicentre, Stratified, Open, Randomized, Comparator-controlled, Parallel-group Phase III Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours|
|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.|
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