Neuroendocrine tumours (NETs) are rare, slow growing, and diagnosis is often delayed with advanced metastases at presentation. In select patient populations, radioisotope therapy with Lutetium-177 (Lu-DOTA-TATE) has been shown to be a safe and effective palliative therapy, and has been widely used by research groups in Europe. A brand of Lu-DOTA-TATE (Lutathera(R)) is approved for the treatment of gastroenteropancreatic NETs in Europe, the U.S., and more recently in Canada. While Lutathera(R) is approved in Canada, it is not publicly funded in Alberta. Lu-DOTA-TATE has been used at the Cross Cancer Institute to treat more than 300 patients with NETs since August, 2010. Our Lu-DOTA-TATE treatment was initially given under Health Canada's Special Access Programme (SAP), with each individual treatment requiring separate approval. In 2014, Health Canada requested we conduct a clinical trial with Lu-DOTA-TATE instead.
The purpose of this study is to: 1) assess the efficacy of Lu-DOTA-TATE treatment in patients with somatostatin receptor positive tumours; 2) assess the safety of Lu-DOTA-TATE; 3) assess the effect of Lu-DOTA-TATE on Quality of Life and survival.
Male or female ≥ 14 - 90 years of age.
At least 1 tumour site reliably evaluable by CT or magnetic resonance imaging (MRI) of at least 1.0 cm (smallest dimension) or ≥ 1.5 cm lymph node disease (smallest dimension) (the target lesion) within 26 weeks of enrolment, with documented presence of somatostatin receptors on radionuclide imaging, with uptake greater than liver background as assessed by planar Octreoscan® images or Ga-68 labelled somatostatin analogue (68Ga-DOTATATE or 68Ga-HA-DOTATATE) PET imaging (or other available somatostatin receptor targeting PET agents) obtained within 1 year of enrolment. Patients with bone-only disease can be enrolled provided there is presence of somatostatin receptor positive tumour(s) on radionuclide imaging corresponding to osteolytic or osteoblastic bone lesions on CT or MRI, with uptake greater than liver background as assessed by planar Ocgtreoscan(R) images or somatostatin receptor PET imaging regardless of size.
Histologically confirmed diagnosis of neuroendocrine tumor.
Progressive disease documented by anatomic imaging and/or presence of new lesions on somatostatin receptor imaging assessed by comparable studies. In the opinion of the investigator, patients with no progression on imaging may still be considered eligible in presence of carcinoid symptoms refractory to treatment with somatostatin receptor analogues or functional Pheochromocytoma/Paraganglioma symptoms that are not well controlled with current medical treatment.
Have previously received Lu-DOTA-TATE therapy.
Potential for surgery with curative intent. Local surgery for symptomatic relief permitted as long as target lesion unaffected.
Major surgery within 12 weeks of enrolment. Minor surgeries such as removal of superficial skin lesions, laser eye surgery, cataract surgery, laparoscopic procedures and other procedures that are minimally invasive are permitted at the Investigator's discretion.
Liver embolization [transcatheter arterial embolization (TAE), TACE, or TARE] within 4 weeks of enrolment.
Single group
[177]Lu-DOTA-TATE
DrugPeptide receptor radionuclide therapy (PPRT)
Change in Tumour response of the target lesion(s) through end of treatment
Tumor response of the target lesions(s) will be assessed by anatomic criteria in reference to RECIST 1.1 used in conjuction with lesion avidity on Nuclear Medicine scans, such as Lu-177 post-therapy scans, Octreoscan, \[68\]Ga-DOTATATE or \[68\]Ga-HA-DOTATATE PET, \[18\]F-FDG PET, \[18\]F-FDOPA PET, and/or others, as clinically indicated.
Median progression-free survival
Time from date of enrolment to the first documented target lesion progression or death due to any cause, which ever occurs first.
Lu-177 scan disease evaluation
A post-therapy Lu-177 scan will be conducted up to 3 days after each Lu-DOTA-TATE treatment to determine the intensity of tumour uptake of Lu-DOTA-TATE and the extent of tumour burden. Changes in Lu-177 scan data will also be used to stratify tumour response.
Change in tumour marker levels
As clinically indicated, serum Chromogranin-A, urinary 5-HIAA, metanephrines, and/or other tumour markers will be collected at baseline, at each re-evaluation, at end of treatment, and at 6 months and 1 year after the last treatment. Tumour marker parameters will be recorded and all changes will be summarized.
Number of participants with adverse events as a measure of safety and tolerability
All participants will be evaluated for AE occurence from treatment 1 up to 5 years after the last treatment.
Change in haematology
Blood samples will be analyzed for hemoglobin, platelet count, white blood cell count, lymphocyte count, and neutrophil count to monitor and record clinically significant out of range values that are indicative of toxicity. Samples will be collected at screening, within 2 weeks prior to each treatment, 6 weeks after each treatment, at each re-evaluation (12-20 weeks after treatments 4, 6, 8, and 10) and at 6 months and 1 year after the last treatment. Changes will be analyzed using descriptive statistics, and any identified adverse events will be tabulated and categorized according to CTCAE v.4.
Change in renal function
Blood samples will be analyzed for creatinine in order to calculate the glomerular filtration rate (GFR) and monitor and record clinically significant out of range values that are indicative of toxicity. Samples will be collected at screening, within 2 weeks prior to each treatment, 6 weeks after each treatment, at each re-evaluation (12-20 weeks after treatments 4, 6, 8, and 10) and at 6 months and 1 year after the last treatment. Changes will be analyzed using descriptive statistics, and any identified adverse events will be tabulated and categorized according to CTCAE v.4.
Change in liver function
Blood samples will be analyzed for total bilirubin, aspartate transaminase, and alanine transaminase to monitor and record clinically significant out of range values that are indicative of toxicity. Samples will be collected at screening, within 2 weeks prior to each treatment, 6 weeks after each treatment, at each re-evaluation (12-20 weeks after treatments 4, 6, 8, and 10) and at 6 months and 1 year after the last treatment. Changes will be analyzed using descriptive statistics, and any identified adverse events will be tabulated and categorized according to CTCAE v.4.
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