Clinical Trials /

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

NCT01876771

Description:

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 available in Alberta yet. This study is being done to provide access to Lu-DOTA-TATE treatment for patients with somatostatin receptor positive tumours. 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.

Related Conditions:
  • Neuroendocrine Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial to Assess the Safety and Effectiveness of Lutetium-177 Octreotate Therapy in Neuroendocrine Tumours
  • Official Title: An Open-label Phase II Study of Lutetium-177 [DOTA0, Tyr3] Octreotate (Lu-DOTA-TATE) Treatment in Patients With Somatostatin Receptor Positive Tumours

Clinical Trial IDs

  • ORG STUDY ID: TX-LUT-001
  • SECONDARY ID: HREBA.CC-18-0165
  • NCT ID: NCT01876771

Conditions

  • Carcinoma, Neuroendocrine

Interventions

DrugSynonymsArms
[177]Lu-DOTA-TATELu-DOTA-TATE[177]Lu-DOTA-TATE Therapy

Purpose

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 available in Alberta yet. This study is being done to provide access to Lu-DOTA-TATE treatment for patients with somatostatin receptor positive tumours. 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.

Detailed Description

      The proposed clinical trial will be a Phase II, open label, single site study in subjects
      with somatostatin receptor positive tumours. Radioactive Lu-DOTA-TATE doses are fixed within
      a range of 1.85 - 5.55 GBq ± 10%, with individual doses based on specified risk factors.
      There will be two groups of subjects enrolled in this study. Group A subjects (primary
      therapy) will have progressive somatostatin receptor positive tumours and have never received
      Lu-DOTA-TATE. Group B subjects (maintenance therapy) will be those subjects who have
      previously received Lu-DOTA-TATE under the Special Access Programme (SAP) and will maintain
      their treatment schedule when they are entered into the study.

      All subjects in Group A will be treated in an induction stage using 10-14 week dosing for up
      to 4 treatments. If an individual patient shows stable or improving disease status with no
      significant toxicities after the 4 induction treatments, they will be assessed 12-20 weeks
      after the last therapeutic treatment for entry into the maintenance stage. Patients will be
      re-assessed for stable or improving disease status with no significant toxicities 12-20 weeks
      after every other treatment of the maintenance stage for consideration of further maintenance
      treatments (re-evaluations), up to a maximum of 8 treatments per patient if there have been
      no significant toxicities or progression. At each treatment, an amino acid solution is
      infused prior to and during the Lu-DOTA-TATE infusion to protect the kidneys. Subjects will
      be followed for 6 months and 1 year (± 4 weeks) following their last treatment dose to
      determine progression-free survival, and for 2, 3, and 5 years (± 4 weeks) following their
      last treatment dose to determine overall survival. All subjects meeting evaluation criteria
      will be analysed for safety, and all Group A subjects who have received at least two
      treatments of Lu-DOTA-TATE will be evaluated for efficacy. Those Group B subjects with
      adequate baseline data for comparison collected retrospectively from a chart review study
      (REV-LUT-001) may also be evaluated for safety and efficacy. Additional optional
      characterization of tumour samples from subjects who have had surgery before or during the
      study may be performed to characterize NET tumour biology changes following Lu-DOTA-TATE
      treatment.
    

Trial Arms

NameTypeDescriptionInterventions
[177]Lu-DOTA-TATE TherapyExperimentalNominal, 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 75 mCi (2.78 GBq) [177]Lu-DOTA-TATE every 22 - 40 weeks, up to a maximum of 8 treatments.
  • [177]Lu-DOTA-TATE

Eligibility Criteria

        Group A (Primary Therapy) Inclusion Criteria:

          1. Male or female ≥ 14 - 90 years of age.

          2. Presence of somatostatin receptor positive tumour(s) 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, with
             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.

          3. Histologically confirmed diagnosis of neuroendocrine tumor.

          4. 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.

          5. 18F-FDG PET/CT whole-body imaging within 26 weeks of enrolment.

          6. Life expectancy greater than 12 weeks from enrollment.

          7. Serum creatinine ≤ 150 µmol/L, and a calculated (Cockcroft-Gault) or estimated GFR of
             ≥ 50 mL/min measured within 2 weeks of enrollment.

          8. 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.

          9. Liver function tests (total bilirubin, alanine transaminase (ALT), aspartate
             transaminase (AST) and alkaline phosphatase) ≤ 3X the limit of normal measured within
             2 weeks of enrolment. Serum albumin ≥ 23 g/L within 2 weeks of enrolment.

         10. Eastern Cooperative Oncology Group (ECOG) Performance Scale Score ≤ 2 measured within
             2 weeks of enrolment.

         11. Provide written informed consent prior to enrolment.

        Group B (Maintenance Therapy) Inclusion Criteria:

          1. Male or female ≥ 14 - 90 years of age.

          2. Have previously received Lu-DOTA-TATE treatment under the SAP.

          3. Life expectancy greater than 12 weeks from enrolment.

          4. 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.

          5. 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.

          6. Liver function tests (total bilirubin, alanine transaminase (ALT), aspartate
             transaminase (AST) and alkaline phosphatase) ≤ 3X the limit of normal measured within
             2 weeks of enrolment. Serum albumin ≥ 23 g/L within 2 weeks of enrolment.

          7. Eastern Cooperative Oncology Group (ECOG) Performance Scale Score ≤ 2 measured within
             2 weeks of enrolment.

          8. Provide written informed consent prior to enrolment.

        Group A (Primary Therapy) Exclusion Criteria:

          1. Have previously received Lu-DOTA-TATE therapy.

          2. Potential for surgery with curative intent. Local surgery for symptomatic relief
             permitted as long as target lesion unaffected.

          3. Surgery within 12 weeks of enrolment. Surgery for removal of superficial skin lesions,
             laser eye surgery, or cataract surgery is permitted.

          4. Liver embolization [transcatheter arterial embolization (TAE), TACE, or TARE] within 4
             weeks of enrolment.

          5. Radioisotope therapy within 12 weeks of enrolment.

          6. Systemic therapy: mTOR inhibitors and tyrosine kinase inhibitors within 6 weeks of
             enrolment; chemotherapy and interferon within 8 weeks of enrolment.

          7. Change in long acting somatostatin analogues, dosage, or dosage frequency within 12
             weeks of enrolment.

          8. Localized external beam irradiation with target lesion(s) in the radiation field.
             Other localized external beam therapy is permitted.

          9. Known brain metastases unless these metastases have been treated and stabilized
             (confirmed by CT) for ≥ 4 months prior to enrolment

         10. Uncontrolled diabetes mellitus defined as random glucose ≥ 2X the upper limit of
             normal (or HbA1c > 10%, if results available) within 12 weeks of enrolment.

         11. 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).

         12. Pregnancy.

         13. Breast feeding.

         14. Prior radiation therapy to more than 25% of the bone marrow.

         15. If, in the opinion of the investigator, other treatments are considered more
             appropriate than the investigational therapy, based on patient and disease
             characteristics.

        Group B (Maintenance Therapy) Exclusion 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 or co-existing malignancies).

          2. Pregnancy.

          3. Breast feeding.
      
Maximum Eligible Age:90 Years
Minimum Eligible Age:14 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in Tumour response of the target lesion(s) through end of treatment
Time Frame:At screening, 12-20 weeks after each treatment cycle, and 6 months and 1 year after the last treatment
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Number of participants with adverse events as a measure of safety and tolerability
Time Frame:Up to 5 years after last treatment
Safety Issue:
Description:All participants will be evaluated for AE occurence from treatment 1 up to 5 years after the last treatment.
Measure:Change in haematology
Time Frame: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.
Safety Issue:
Description: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.
Measure:Change in renal function
Time Frame: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
Safety Issue:
Description: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.
Measure:Change in liver function
Time Frame: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
Safety Issue:
Description: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.
Measure:Median and 3-year overall survival
Time Frame:Up to 3 years after last treatment
Safety Issue:
Description:Time from date of enrolment to date of death due to any cause or date of censoring at the last time the participant was known to be alive.
Measure:Change in Quality of Life (EORTC QLQ)
Time Frame:Prior to each treatment
Safety Issue:
Description:The European Organisation for Research Treatment of Cancer (EORTC) QLQ-C30 v.3 in conjunction with the supplementary module QLQ-GI.NET21 Quality of Life questionnaires will be administered prior to each treatment on the visit date. The core questionnaire and supplementary module will be scored according to the scoring manual, and changes analyzed to assess the effect of Lu-DOTA-TATE treatment on Quality of Life.
Measure:Change in Quality of Life (ESAS-r)
Time Frame:Prior to each treatment
Safety Issue:
Description:The Edmonton Symptom Assessment System Revised (ESAS-r) will be administered prior to each treatment on visit date. The questionnaire will be scored according to the scoring manual, and changes analyzed to assess the effect of Lu-DOTA-TATE treatment on Quality of Life.
Measure:Change in tumour biology (optional)
Time Frame:Up to 1 year after last treatment
Safety Issue:
Description:Subjects who have had surgery prior to or after Lu-DOTA-TATE therapy may have existing tumour tissue sample tested to characterize NET tumour biology and the effects of Lu-DOTA-TATE therapy on tumour cell function.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AHS Cancer Control Alberta

Trial Keywords

  • 177lutetium-DOTA(O)Tyr3)octreotate

Last Updated

June 18, 2020