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. Lu-DOTA-TATE has been used at the Cross Cancer Institute to treat more than 200 patients with NETs since August, 2010. This study is being done because the Lu-DOTA-TATE treatment was initially given under Health Canada's Special Access Programme (SAP), with each individual treatment requiring separate approval. Health Canada requested that the investigators conduct a clinical trial with Lu-DOTA-TATE, with the goal of receiving approval to use Lu-DOTA-TATE as a marketed treatment agent. The purpose of this study is to: 1) assess the efficacy of Lu-DOTA-TATE treatment in patients with somatostatin receptor positive tumours; 2) and assess the safety of Lu-DOTA-TATE.

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: Ethics # 26064
  • 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. Lu-DOTA-TATE has been used at the Cross Cancer Institute to treat more than 200 patients with NETs since August, 2010. This study is being done because the Lu-DOTA-TATE treatment was initially given under Health Canada's Special Access Programme (SAP), with each individual treatment requiring separate approval. Health Canada requested that the investigators conduct a clinical trial with Lu-DOTA-TATE, with the goal of receiving approval to use Lu-DOTA-TATE as a marketed treatment agent. The purpose of this study is to: 1) assess the efficacy of Lu-DOTA-TATE treatment in patients with somatostatin receptor positive tumours; 2) and assess the safety of Lu-DOTA-TATE.

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 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 the last treatment of each cycle (1 cycle = 2 treatments at 22-40 week intervals) of
      the maintenance stage for consideration of further maintenance cycles (re-evaluations), up to
      a maximum of 4 cycles 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.
      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 (progression free survival and effect on Quality of Life). 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) [either histologically or
             radionuclide imaging proven (Octreoscan or Ga-68 Dotatate / NETSPOT)], 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) within 26 weeks of enrolment.

          3. Life expectancy greater than 12 weeks from enrollment.

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

          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) ≤ 5X 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 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) ≤ 5X 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.

        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 (modified RECIST criteria, CT/MRI or Lu-177 scan) of the target lesion through end of treatment
Time Frame:At screening, 12-20 weeks after each treatment cycle, and 6 months and 1 year after the last maintenance stage treatment
Safety Issue:
Description:Tumor response of the target lesions(s) identified by CT/MRI or Lu-177 scan is assessed at each re-evaluation, and at 6 months and 1 year after the last maintenance stage treatment. If a target lesion outside of the liver cannot be identified using the Lu-177 scan, CT/MRI will be used to identify a target lesion in the liver to evaluate tumour response and disease status.

Secondary Outcome Measures

Measure:Number of participants with adverse events as a measure of safety and tolerability
Time Frame:Up to 1 year after last treatment
Safety Issue:
Description:All participants will be evaluated for AE occurence from treatment 1 up to 1 year after the last treatment.
Measure:Change in pulse (bpm)
Time Frame:within 30 min prior to start of amino acid through to within 30 min of amino acid end for each treatment
Safety Issue:
Description:Pulse is measured at each treatment visit: 1) 30 min prior to start of amino acid infusion; 2) 15 min prior to the start of the Lu-DOTA-TATE infusion; 3) 10-20 min after the start of the Lu-DOTA-TATE infusion; 4) 15 min after the Lu-DOTA-TATE infusion ends; 5) and within 30 min after the amino acid infusion ends. 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 blood pressure (mm Hg)
Time Frame:within 30 min prior to start of amino acid through to within 30 min of amino acid end for each treatment
Safety Issue:
Description:Blood pressure is measured at each treatment visit: 1) 30 min prior to start of amino acid infusion; 2) 15 min prior to the start of the Lu-DOTA-TATE infusion; 3) 10-20 min after the start of the Lu-DOTA-TATE infusion; 4) 15 min after the Lu-DOTA-TATE infusion ends; 5) and within 30 min after the amino acid infusion ends. 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 oxygen saturation (%)
Time Frame:within 30 min prior to start of amino acid through to within 30 min of amino acid end for each treatment
Safety Issue:
Description:Oxygen saturation is measured at each treatment visit: 1) 30 min prior to start of amino acid infusion; 2) 15 min prior to the start of the Lu-DOTA-TATE infusion; 3) 10-20 min after the start of the Lu-DOTA-TATE infusion; 4) 15 min after the Lu-DOTA-TATE infusion ends; 5) and within 30 min after the amino acid infusion ends. 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 haematology (CBC & Differential) / biochemistry (SMA-12 panel)
Time Frame:Within 2 weeks prior to each treatment to 1 year after last treatment.
Safety Issue:
Description:Blood samples are collected: 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:Within 2 weeks prior to each treatment to 1 year after last treatment.
Safety Issue:
Description:GFR will be monitored from blood samples collected: 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 summarized.
Measure:Change in Quality of Life
Time Frame:Prior to each treatment and up to 1 year after last treatment
Safety Issue:
Description:The 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, and at 6 months and 1 year after the last treatment. 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
Time Frame:Prior to each treatment and up to 1 year after last treatment
Safety Issue:
Description:The Edmonton Symptom Assessment System Revised (ESAS-r) will be administered prior to each treatment on visit date, and at 6 months and 1 year after the last treatment. 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

November 16, 2017