A Trial to Assess the Safety and Effectiveness of Lutetium-177 Octreotate Therapy in Neuroendocrine Tumours

NCT01876771 | Recruiting Phase 2

• 2 other identifiers: TX-LUT-001HREBA.CC-18-0165
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Carcinoma, Neuroendocrine

Keywords

177lutetium-DOTA(O)Tyr3)octreotate

Outcome Measures

Primary Outcomes (4)

• 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.

  At screening, 12-20 weeks after each treatment cycle, and 6 months and 1 year after the last treatment

• 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.

  Up to 1 year after last treatment

• 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.

  Up to 3 days after each Lu-DOTA-TATE treatment

• 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.

  At baseline, 12-20 weeks after each treatment cycle, and 6 months and 1 year after last treatment

Secondary Outcomes (8)

• Number of participants with adverse events as a measure of safety and tolerability

  Up to 5 years after last treatment

• Change in haematology

  At screening, within 2 weeks prior to at 6 weeks after each treatment, at each re-evaluation, and at 6 months and 1 year after last treatment.

• Change in renal function

  At screening, within 2 weeks prior to at 6 weeks after each treatment, at each re-evaluation, and at 6 months and 1 year after last treatment

• Change in liver function

  At screening, within 2 weeks prior to at 6 weeks after each treatment, at each re-evaluation, and at 6 months and 1 year after last treatment

• Median, 1, 2, 3, 4, and 5-year overall survival

  Up to 5 years after last treatment

Study Arms (1)

[177]Lu-DOTA-TATE Therapy

EXPERIMENTAL

Nominal, induction stage dose of 150 mCi (5.55 GBq) \[177\]Lu-DOTA-TATE every 10 - 14 weeks for 4 treatments. Nominal maintenance stage dose of 100 mCi (3.7 GBq) \[177\]Lu-DOTA-TATE every 22 - 40 weeks, up to a maximum of 8 treatments.

Drug: [177]Lu-DOTA-TATE

Interventions

[177]Lu-DOTA-TATE DRUG

Peptide receptor radionuclide therapy (PPRT)

Also known as: Lu-DOTA-TATE

[177]Lu-DOTA-TATE Therapy

Eligibility Criteria

• Age: 14 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• F-FDG PET/CT whole-body imaging within 26 weeks of enrolment.
• Life expectancy greater than 12 weeks from enrollment.
• Serum creatinine ≤ 150 µmol/L, and a calculated (Cockcroft-Gault) or estimated GFR of ≥ 50 mL/min measured within 2 weeks of enrollment.
• Haemoglobin concentration ≥ 90 g/L; white blood cell (WBC) count ≥ 2 x 10\^9/L; platelets ≥ 100 x 10\^9/L measured within 2 weeks of enrolment.
• Liver function tests (total bilirubin, alanine transaminase (ALT), aspartate transaminase (AST)) ≤ 3X the limit of normal measured within 2 weeks of enrolment. Serum albumin ≥ 23 g/L within 2 weeks of enrolment.
• Eastern Cooperative Oncology Group (ECOG) Performance Scale Score ≤ 2 measured within 2 weeks of enrolment.
• Provide written informed consent prior to enrolment.
• Male or female ≥ 14 - 90 years of age.
• Have previously received Lu-DOTA-TATE treatment under the SAP.
• Life expectancy greater than 12 weeks from enrolment.
• Serum creatinine ≤ 150 μmol/L, and a calculated (Cockcroft-Gault) or estimated glomerular filtration rate (GFR) of ≥ 50 mL/min measured within 2 weeks of enrolment.

You may not qualify if:

• 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.
• Radioisotope therapy within 12 weeks of enrolment.
• Systemic therapy: mTOR inhibitors and tyrosine kinase inhibitors within 6 weeks of enrolment; chemotherapy and interferon within 8 weeks of enrolment.
• Change in long-acting somatostatin analogues, dosage, or dosage frequency within 12 weeks of enrolment unless changes are required to manage uncontrolled symptoms.
• Localized external beam irradiation with target lesion(s) in the radiation field. Other localized external beam therapy is permitted.
• Known brain metastases unless these metastases have been treated and stabilized (confirmed by CT) for ≥ 4 months prior to enrolment
• Uncontrolled diabetes mellitus defined as random glucose ≥ 2X the upper limit of normal (or HbA1c \> 10%, if results available) within 12 weeks of enrolment.
• 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).
• Pregnancy.
• Breast feeding.
• Prior radiation therapy to more than 25% of the bone marrow.
• If, in the opinion of the investigator, other treatments are considered more appropriate than the investigational therapy, based on patient and disease characteristics.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead

Study Sites (1)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

MeSH Terms

Conditions

Carcinoma, Neuroendocrine

Interventions

lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Donald W Morrish, MD, PhD

  Professor of Endocrinology and Oncology, University of Alberta, Cross Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NET Coordinator

CONTACT

780-577-8080; ACB.NeuroEndocrine@ahs.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2013
• First Posted: June 13, 2013
• Study Start: April 29, 2014
• Primary Completion (Estimated): December 1, 2042
• Study Completion (Estimated): December 1, 2042
• Last Updated: August 8, 2025

Record last verified: 2025-08

Locations

CA (1)