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EAP 177Lu-DOTA0-Tyr3-Octreotate for Inoperable, SSR+, NETs, Progressive Under SSA Tx

Conditions
Neuroendocrine Tumors
Registration Number
NCT02705313
Lead Sponsor
Advanced Accelerator Applications
Brief Summary

Advanced Accelerator Applications is currently pursuing marketing approval for 177Lu-DOTA0-Tyr3-Octreotate (Lutathera). This expanded access therapeutic protocol aims to allow patients suffering from inoperable, somatostatin receptor positive, neuroendocrine tumors, progressive under somatostatin analogue therapy to access the investigational product, 177Lu-DOTA0-Tyr3-Octreotate (Lutathera), prior to its commercial availability.

Detailed Description

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.

Recruitment & Eligibility

Status
APPROVED_FOR_MARKETING
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • 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)
Exclusion Criteria
  • 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.

Study & Design

Study Type
EXPANDED_ACCESS
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (40)

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

University of California, San Francisco

🇺🇸

San Francisco, California, United States

University of California, Los Angeles

🇺🇸

Los Angeles, California, United States

Northwestern Medicine

🇺🇸

Chicago, Illinois, United States

Duke University Hospital

🇺🇸

Durham, North Carolina, United States

Lenox Hill Hospital

🇺🇸

New York, New York, United States

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

UT Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Bon Secours Medical Group/ Saint Francis Hospital Cancer Center

🇺🇸

Greenville, South Carolina, United States

Rocky Mountain Cancer Centers

🇺🇸

Denver, Colorado, United States

Johns Hopkins Outpatient Center

🇺🇸

Baltimore, Maryland, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

University of Utah, Huntsman Cancer Institute

🇺🇸

Salt Lake City, Utah, United States

Cancer Treatment Center of America - Southeastern Regional Medical Center

🇺🇸

Newnan, Georgia, United States

Stanford University Medical Center

🇺🇸

Stanford, California, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

Banner M.D. Anderson Cancer Center

🇺🇸

Gilbert, Arizona, United States

Mayo Clinic Hospital

🇺🇸

Phoenix, Arizona, United States

University of Colorado Hospital - Anschutz Cancer Pavilion

🇺🇸

Aurora, Colorado, United States

The Ohio State University James Cancer Center

🇺🇸

Columbus, Ohio, United States

The University of Iowa Hospitals & Clinics (UIHC) including the Carver College of Medicine

🇺🇸

Iowa City, Iowa, United States

Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

CHI Health West Omaha Imaging Center

🇺🇸

Omaha, Nebraska, United States

Emory University Hospital

🇺🇸

Atlanta, Georgia, United States

Virginia Mason Medical Center

🇺🇸

Seattle, Washington, United States

Washington University School of Medicine Siteman Cancer Center

🇺🇸

Saint Louis, Missouri, United States

University of Washington, Department of Radiology, Division of Nuclear Medicine

🇺🇸

Seattle, Washington, United States

Ochsner Medical Center

🇺🇸

Kenner, Louisiana, United States

Kansas City Research Institute

🇺🇸

Kansas City, Missouri, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Carilion Clinic

🇺🇸

Roanoke, Virginia, United States

Kaiser Permanente, Santa Clara Homestead

🇺🇸

Santa Clara, California, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Montefiore Einstein Center for Cancer Care

🇺🇸

Bronx, New York, United States

City of Hope (City of Hope Medical Center, City of Hope National Medical Center)

🇺🇸

Duarte, California, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

🇺🇸

Dallas, Texas, United States

Stony Brook Cancer Center

🇺🇸

Stony Brook, New York, United States

University of Pittsburgh, Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

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