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Clinical Trial Details — Status: Approved for marketing

Administrative data

NCT number NCT02705313
Other study ID # AAA-177Lu-03
Secondary ID
Status Approved for marketing
Phase
First received March 7, 2016
Last updated April 5, 2018

Study information

Verified date April 2018
Source Advanced Accelerator Applications
Contact n/a
Is FDA regulated No
Health authority
Study type Expanded Access

Clinical Trial 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.


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 information / eligibility

Status Approved for marketing
Enrollment 0
Est. completion date
Est. primary completion date
Accepts healthy volunteers
Gender All
Age group 18 Years and older
Eligibility 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


Related Conditions & MeSH terms


Intervention

Drug:
177Lu-DOTA0-Tyr3-Octreotate
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.

Locations

Country Name City State
United States Emory University Hospital Atlanta Georgia
United States University of Colorado Hospital - Anschutz Cancer Pavilion Aurora Colorado
United States Johns Hopkins Outpatient Center Baltimore Maryland
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Montefiore Einstein Center for Cancer Care Bronx New York
United States Roswell Park Cancer Institute Buffalo New York
United States Northwestern Medicine Chicago Illinois
United States Rush University Medical Center Chicago Illinois
United States The Ohio State University James Cancer Center Columbus Ohio
United States Texas Oncology - Baylor Charles A. Sammons Cancer Center Dallas Texas
United States UT Southwestern Medical Center Dallas Texas
United States Rocky Mountain Cancer Centers Denver Colorado
United States Karmanos Cancer Institute Detroit Michigan
United States City of Hope (City of Hope Medical Center, City of Hope National Medical Center) Duarte California
United States Duke University Hospital Durham North Carolina
United States Banner M.D. Anderson Cancer Center Gilbert Arizona
United States Bon Secours Medical Group/ Saint Francis Hospital Cancer Center Greenville South Carolina
United States The University of Iowa Hospitals & Clinics (UIHC) including the Carver College of Medicine Iowa City Iowa
United States Mayo Clinic Jacksonville Florida
United States Kansas City Research Institute Kansas City Missouri
United States Ochsner Medical Center Kenner Louisiana
United States University of California, Los Angeles Los Angeles California
United States Icahn School of Medicine at Mount Sinai New York New York
United States Lenox Hill Hospital New York New York
United States Memorial Sloan Kettering Cancer Center New York New York
United States Cancer Treatment Center of America - Southeastern Regional Medical Center Newnan Georgia
United States CHI Health West Omaha Imaging Center Omaha Nebraska
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States Mayo Clinic Hospital Phoenix Arizona
United States University of Pittsburgh, Medical Center Pittsburgh Pennsylvania
United States Carilion Clinic Roanoke Virginia
United States Mayo Clinic Rochester Minnesota
United States Washington University School of Medicine Siteman Cancer Center Saint Louis Missouri
United States University of Utah, Huntsman Cancer Institute Salt Lake City Utah
United States University of California, San Francisco San Francisco California
United States Kaiser Permanente, Santa Clara Homestead Santa Clara California
United States University of Washington, Department of Radiology, Division of Nuclear Medicine Seattle Washington
United States Virginia Mason Medical Center Seattle Washington
United States Stanford University Medical Center Stanford California
United States Stony Brook Cancer Center Stony Brook New York
United States Moffitt Cancer Center Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
Advanced Accelerator Applications

Country where clinical trial is conducted

United States, 

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