Advanced Accelerator Applications activated in 2012 a multicenter, stratified, open, randomized, comparator-controlled, parallel-group Phase III study comparing treatment with 177Lu-DOTA0-Tyr3-Octreotate to 60 mg Octreotide LAR in patients with inoperable, progressive, somatostatin receptor positive, midgut carcinoid tumors (NETTER-1 trial, EudraCT number 2011-005049-11, IND number 77219). Clinical studies, including NETTER-1 for which the primary analysis has been conducted, showed clinical evidence of safety and effectiveness to support the expanded access use without any unreasonable potential risks for the patients in the context of the disease to be treated. In July 2016, the first patient was treated under an Expanded Access Program (EAP) for inoperable, progressive, somatostatin receptor positive, midgut carcinoid tumors. Compassionate use programs in Europe include pulmonary NETs. In the US, there were many centers with patients with NETs who did not meet the inclusion criteria for the original EAP. In May 2017, Advanced Accelerator Applications inquired with the FDA if amending the inclusion criteria of the original protocol to include all NETs would be permissible. In June 2017, Advanced Accelerator Applications was able to submit a revision to the original Expanded Access Program's protocol for 177Lu-DOTA0-Tyr3-Octreotate to include neuroendocrine tumors arising from sites other than midgut. The locations listed below that are participating in the EAP may have received IRB approval for either the original protocol or the new protocol or both. Please, inquire with the Facility Contact as to which protocol is active at their site.
The treatment regimen consists of 4 administrations of 7.4 GBq (200 mCi) at the date and time of infusion. The recommended interval between two infusions is 8 weeks, which could be extended up to 16 weeks in case of dose modifying toxicity.
Other Name: Lutathera
- Presence of metastasized or locally advanced neuroendocrine tumor, inoperable (curative intent) at enrollment time, and regardless of the origin of the 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)
- 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).
- 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.
Banner M.D. Anderson Cancer Center
Gilbert, Arizona, 85234
Mayo Clinic Hospital
Phoenix, Arizona, 85054
City of Hope (City of Hope Medical Center, City of Hope National Medical Center)
Duarte, California, 91010
University of California, Los Angeles
Los Angeles, California, 90095
University of California, San Francisco
San Francisco, California, 94143
Kaiser Permanente, Santa Clara Homestead
Santa Clara, California, 95051
Stanford University Medical Center
Stanford, California, 94305
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, 80045
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Jacksonville, Florida, 32224
Moffitt Cancer Center
Tampa, Florida, 33612
Emory University Hospital
Atlanta, Georgia, 30322
Cancer Treatment Center of America - Southeastern Regional Medical Center
Newnan, Georgia, 30265
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
The University of Iowa Hospitals & Clinics (UIHC) including the Carver College of Medicine
Iowa City, Iowa, 52242
Ochsner Medical Center
Kenner, Louisiana, 70065
Johns Hopkins Outpatient Center
Baltimore, Maryland, 21287
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Karmanos Cancer Institute
Detroit, Michigan, 48201
Rochester, Minnesota, 55905
Kansas City Research Institute
Kansas City, Missouri, 64131
Washington University School of Medicine Siteman Cancer Center
Saint Louis, Missouri, 63110
CHI Health West Omaha Imaging Center
Omaha, Nebraska, 68130
Montefiore Einstein Center for Cancer Care
Bronx, New York, 10467
Roswell Park Cancer Institute
Buffalo, New York, 14263
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Lenox Hill Hospital
New York, New York, 10075
Stony Brook Cancer Center
Stony Brook, New York, 11794
Duke University Hospital
Durham, North Carolina, 27710
The Ohio State University James Cancer Center
Columbus, Ohio, 43210
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of Pittsburgh, Medical Center
Pittsburgh, Pennsylvania, 15213
Bon Secours Medical Group/ Saint Francis Hospital Cancer Center
Greenville, South Carolina, 29697
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
UT Southwestern Medical Center
Dallas, Texas, 75390
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Roanoke, Virginia, 24014
Virginia Mason Medical Center
Seattle, Washington, 98101
University of Washington, Department of Radiology, Division of Nuclear Medicine
Seattle, Washington, 98185
Expanded Access program information for companies listed in the Expanded Access Company Directory is pulled daily from ClinicalTrials.gov, a resource provided by the National Institutes of Health in cooperation with the U.S. Food and Drug Administration. Click here for more information about ClinicalTrials.gov.