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

Neuroendocrine Tumors Clinical Trial

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

Clinical Trial Details — Status: Approved for marketing

Administrative data

• NCT number: NCT02705313
• Other study ID #: AAA-177Lu-03
• Status: Approved for marketing
• 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
• 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
• 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.

Related Conditions & MeSH terms

• Neuroendocrine Tumors

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,