Expanded Access Protocol for Therapeutic Use of 177Lu-DOTA0-Tyr3-Octreotate in Patients With Inoperable, Somatostatin Receptor Positive, Midgut Carcinoid Tumors, Progressive Under Somatostatin Analogue Therapy
Advanced Accelerator Applications is currently pursuing marketing approval for 177Lu-DOTA0-Tyr3-Octreotate (Lutathera). Considering that Phase III NETTER-1 clinical trial recruitment has been completed, this expanded access therapeutic protocol aims to allow patients suffering from inoperable, somatostatin receptor positive, midgut carcinoid tumors, progressive under somatostatin analogue therapy to access the investigational product, 177Lu-DOTA0-Tyr3-Octreotate (Lutathera), prior to its commercial availability.
Presence of metastasized or locally advanced, inoperable (curative intent) at enrollment time, midgut carcinoid tumor.
Ki67 index ≤ 20%
Patients progressive under SSA (any dose) at the time of enrollment
Target lesions over-expressing somatostatin receptors according to an appropriate imaging method (e.g. 111In-pentetreotide (Octreoscan) imaging or 68Ga-DOTA0-Tyr3-Octreotate (or 68Ga-edotreotide) imaging)
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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).
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).
Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency ablation within 12 weeks prior to enrollment.
Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks prior to enrollment.
Known brain metastases, unless these metastases have been treated and stabilized.
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 4 weeks before the administration of 177Lu-DOTA0-Tyr3-Octreotate, unless the tumor uptake on target lesions is at least as high as normal liver uptake.
Patients with any other significant medical, psychiatric, or surgical condition,currently uncontrolled by treatment, which may pose a risk to the patient safety
Prior external beam radiation therapy to more than 25% of the bone marrow.
Current spontaneous urinary incontinence making impossible the safe administration of the radioactive IMP.
Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and with no evidence of recurrence.
Patients who have not provided a signed informed consent form to accept this treatment.
University of California, San Francisco San Francisco, California, 94143, USA
Stanford University Medical Center Stanford, California, 94305, USA
University of California, Los Angeles Los Angeles, California, 90095, USA