An Open Label Registry Study of Lutetium-177 (DOTA0, TYR3) Octreotate (Lu-DOTA-TATE) Treatment in Patients with Somatostatin Receptor Positive Tumours

An Open Label Phase II, Registry Study of Lutetium-177 (DOTA0, TYR3) Octreotate (Lu-DOTA-TATE) Treatment in Patients with Somatostatin Receptor Positive Tumours

Lu-DOTA-TATE (Lutetium-177 octreotate) is a radiopharmaceutical that has been reported as being effective in controlling symptoms and increase quality of life; induce stable disease and extend progression free survival; induce a (good) partial remission and induce a complete remission in patients with a somatostatin receptor positive tumour.

The purpose of this study is to assess the efficacy of Lu-DOTA-TATE by measuring progression free survival and overall survival. This study will also asses the safety of Lu-DOTA-TATE, and the quality of life of the patients treated with Lu-DOTA-TATE.

Neuroendocrine (NET) tumours have secretory and metabolic pathways not typically found in other cancers that can be utilized for molecular imaging and therapeutic targeting. The most important is somatostatin. Somatostatin receptors are useful tools in the diagnosis and treatment of NET tumours because the somatostatin analogue octreotate can be radiolabeled with lutetium-177 for imaging and therapy.

In selected populations of patients, radioisotope therapy in expert hands has been shown to be a safe and effective palliative therapy with stable disease, progression free survival benefit, symptom control and improvements in quality of life. Lutetium-177 (DOTA0, Tyr3) octreotate has been used in a significant number of clinical studies shown to be safe and effective as a therapeutic agent in patients with NET tumours. The investigators intend to further confirm these benefits with lutetium-177 octreotate, which could form the basis for a national registry study leading to registration of this therapeutic intervention.

Inclusion Criteria:

Group A: Primary therapy subjects will be included in the study if they meet all of the following general criteria:

1. Male or female ≥ 14 - 90 years of age. If female of child-bearing potential and outside of the window of 10 days since the first day of the last menstrual period, a negative pregnancy test is required.
2. Presence of somatostatin receptor positive tumour(s) (either histologically or Octreoscan image proven), with at least 1 tumour site reliably evaluable by CT or MRI of at least 1.5 cm (smallest dimension) with respect to RECIST criteria (the target lesion).
3. Presence of somatostatin receptors on (at least) the target lesion demonstrated by uptake of OctreoScan® at least equal to liver uptake within 12 weeks of enrollment.
4. Life expectancy greater than 26 weeks from enrollment.
5. Serum creatinine ≤ 130 μmol/L, and a measured glomerular filtration rate (GFR) using plasma clearance of ≥50 mL/min measured within 2 weeks of enrollment.
6. Haemoglobin concentration ≥ 90 g/L; white blood cell count (WBC) ≥ 3 x 109/L; platelets ≥ 100 x 109/L measured within 2 weeks of enrollment.
7. Liver function tests (serum albumin, total bilirubin, alanine amniotransferase (ALT),aspartate aminotransferase (AST) and alkaline phosphatase) ≤ 3 X the limit of normal.
8. Eastern Cooperative Oncology Group (ECOG) Performance Scale Score ≤ 2 measured within 2 weeks of enrollment.
9. Provide written informed consent prior to enrollment.
10. Ki 67 < 20%, unless patients has been treated with chemotherapy and lesions are stable (Ki 67 < 30%)

Group B: Secondary therapy subjects will be included in the study if they meet all of the following general criteria:

1. Male or female ≥ 14 - 90 years of age. If female of child-bearing potential and outside of the window of 10 days since the first day of the last menstrual period, a negative pregnancy test is required.
2. Have received Lu-DOTA-TATE treatment at the London Health Sciences Centre under the Special Access Programed or other radionuclide therapy for neuroendocrine tumor.
3. Provide written informed consent prior to enrollment.

Exclusion Criteria:

Group A: Primary therapy subjects will be excluded from the study if they meet any of the following criteria:

1. Potential for surgery with curative intent. Local surgery for symptomatic relief permitted as long as target lesion unaffected.
2. Surgery, radiation therapy, radioisotope therapy, change in Sandostatin LAR therapy dosage, cytotoxic chemotherapy, embolization or other investigative therapy [interferons, mammalian target of rapamycin (mTOR) inhibitors] within 12 weeks of enrollment. Localized external beam irradiation permitted as long as target lesion unaffected.
3. Known brain metastases unless these metastases have been treated or stable (confirmed by CT) for ≥ 6 months prior to enrollment
4. Uncontrolled diabetes mellitus defined as fasting glucose ≥ 3 X the upper limit of normal within 12 weeks of enrollment.
5. Another significant medical, psychiatric or surgical condition uncontrolled by treatment, which may interfere with completion or conduct of the study (such as urinary incontinence, co-existing malignancies).
6. Pregnancy.
7. Breast feeding.
8. Prior radiation therapy to more than 25% of the bone marrow.

Group B: Secondary therapy subjects will be excluded from the study if they meet any of the following criteria:

1. Another significant medical, psychiatric or surgical condition uncontrolled by treatment, which may interfere with completion or conduct of the study (such as urinary incontinence, co-existing malignancies).
2. Pregnancy.
3. Breast feeding.