A multicenter, stratified, open, randomized, comparator-controlled, parallelgroup 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.
- Conditions
- Patients with inoperable, progressive, OctreoScan® positive, well-differentiated neuroendocrine tumours of the small bowel (midgut carcinoid tumours), who are treated with 20 mg or 30 mg Octreotide LAR at a fixed dose for at least 12 weeks prior to enrolment in the study.MedDRA version: 14.1Level: LLTClassification code 10062392Term: Carcinoid tumor of the small bowelSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10052399Term: Neuroendocrine tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-005049-11-ES
- Lead Sponsor
- Advanced Accelerator Applications
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 231
1.Presence of inoperable (curative intent) at enrolment time, histologically proven, midgut carcinoid tumour.
2.Ki67 index = 20%.
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 enrolment in the study.
4.Patients =18 years of age.
5.Patients must have progressive disease based on RECIST Criteria, Version 1.1 (Appendix 2) evidenced with CT scans/MRI obtained within 3 years from enrolment; previous images must be centrally evaluated to confirm the disease progression under previous therapy: for the purpose of determining disease progression the oldest CT/MRI scan must not be older than 3 years and the most recent scan must not be older than 4 weeks from the projected randomization date. The CT scan/MRI scan should be one that was performed while the patient was on a fixed dose of Sandostatin LAR.
6.Confirmed presence of somatostatin receptors on all technically evaluable tumour lesions documented by CT/MRI scans, based on positive OctreoScan® imaging within 24 weeks prior to enrolment in the study.
7.The tumour uptake observed using OctreoScan® should be ? normal liver uptake observed on planar imaging (Appendices 5 and 6).
8.Karnofsky Performance Score (KPS) =60
9.Presence of at least 1 measurable site of disease.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.Serum creatinine >150 µmol/L or 1.7 mg/dL, or a measured creatinine clearance (or measured glomerular filtration rate (GFR) using plasma clearance methods, not gamma camera-based) of <50 mL/min.
2.Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x10^9/L (2000/mm3); platelets <75x10^9/L (75x10^3/mm3).
3.Total bilirubin >3 x ULN.
4.Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
5.Pregnancy (see protocol Appendix 7).
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 enrolment in the study.
8.Peptide receptor radionuclide therapy (PRRT) at any time prior to enrolment in the study.
9.Targeted surgery, radiotherapy (external beam), chemotherapy, embolization, interferons, mTOR-inhibitors or other investigational therapy within 12 weeks prior to enrolment in the study.
10.Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrolment in the study. Patients with a history of brain metastases must have a head CT with contrast to document stable disease prior to enrolment in the study.
11.Uncontrolled congestive heart failure (NYHA II, III, IV).
12.Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.
13.Any patient who has both OctreoScan® positive and negative tumours.
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 observed by OctreoScan® imaging during continued Octreotide treatment is at least as high as normal liver uptake observed by planar imaging (Appendices 5 and 6).
15.Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study.
16.Prior external beam radiation therapy to more than 25% of the bone marrow.
17.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 an informed consent form to participate in the study, obtained prior to the start of any protocol related activities.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method