Clinical trial NCT02705313: EAP 177Lu-DOTA0-Tyr3-Octreotate for Inoperable, SSR+, NETs, Progressive Under SSA Tx
Official title: Expanded Access Protocol for Therapeutic Use of 177Lu-DOTA0-Tyr3-Octreotate in Patients With Inoperable, Somatostatin Receptor Positive, Neuroendocrine Tumors, Progressive Under Somatostatin Analogue Therapy
Study type: EXPANDED_ACCESS
Overall status: APPROVED_FOR_MARKETING
Conditions: Neuroendocrine Tumors
Keywords: neuroendocrine tumors
177Lu-DOTA0-Tyr3-Octreotate
PRRT
Lead sponsor: Advanced Accelerator Applications
Sponsor class: INDUSTRY
First posted: 2016-03-10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT

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.

Eligibility criteria: 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.

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