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Carcinoid Heart Disease and Peptide Receptor Radiotargetted Therapy (CHARRT)

Primary Purpose

Carcinoid Heart Disease, Carcinoid Syndrome, Carcinoid Tumor

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Lutathera
Sponsored by
King's College Hospital NHS Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoid Heart Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Echocardiographic evidence of mild/ moderate carcinoid heart disease.
  2. Carcinoid syndrome with Echocardiographic evidence of carcinoid heart disease- to be defined further
  3. Elevated urinary 5-HIAA or NYHA class I or II on therapy [not necessarily exceeding label dose of SSA LAR; eg, could be 30mg SMS LAR plus sc SMS for breakthrough]
  4. Presence of metastasized or locally advanced, inoperable (curative intent) histologically proven, Grade 1 or Grade 2 gastroenteropancreatic neuroendocrine (GEP-NET) or Lung-NET tumor
  5. Age >18
  6. Ki67 index ≤ 20%
  7. Patients who have provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related activities
  8. Confirmed presence of somatostatin receptors on all target lesions documented by CT/MRI scans, within 8 weeks prior to randomization (centrally confirmed), as assessed by the following somatostatin receptor imaging (SRI) modalities: [68Ga]-DOTA-TOC (Somakit-TOC™) PET/CT imaging or [68Ga]-DOTA-TATE PET/CT imaging (NETSPOTTM) or Somatostatin Receptor scintigraphy (SRS) with 111In-pentetreotide (Octreoscan®).

10. Irresectable disease 11. Karnofsky Performance Score (KPS) ≥60.

Exclusion Criteria:

  1. Patients with progressive disease by RECIST progressed within 6 months
  2. Unable to consent
  3. Pregnant
  4. Chemotherapy within 3 months
  5. PRRT within 3 years
  6. Grade 3 tumours (WHO 2010)
  7. Severe or Uncontrolled carcinoid heart disease
  8. Renal impairment with eGRF <40 ml/min
  9. NYHA class III,IV

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    No Intervention

    Arm Label

    Lutathera Treatment Arm

    Best Supportive Care

    Arm Description

    • 4x cycles of 7.4 GBq (200mCi) of Lutathera therapy (177Lu-DOTA0-Tyr3-Octreotate) with concomitant amino acids for participants randomised onto the Lutathera therapy arm, every 8 weeks, plus long term somatostatin analogues (SSTA).

    Somatostatin analogue treatment according to current standard, routine care

    Outcomes

    Primary Outcome Measures

    The rate of progression of moderate carcinoid heart disease (CHD)
    The rate of progression of carcinoid heart disease (CHD) in patients with moderate CHD will be compared across the Lutathera Therapy and Best Supportive Care Arms and will be assessed through RECIST CT/MRI imaging and urinary 5-HIAA levels throughout the duration of the study. The rate of progression will be assessed at each study visit across both arms during the intervention and follow-up phase. If the study treatment is successful in delaying the rate of progression, then the rate of progression in the Lutathera (study intervention) arm is expected to be much slower than in the Best Supportive Care arm.

    Secondary Outcome Measures

    Change in NYHA heart failure score
    The association between Lutathera Therapy against Best Supportive Care will be assessed by comparing the change in NYHA heart failure score in patients enrolled in both study arms. The NYHA Heart Failure Score is grade I to IV, with Grade I being No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath) and Grade IV being Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. The change in grade will be assessed with an anticipated reduction in grade if the study treatment is successful in reducing symptoms.
    Progressive disease
    Progressive disease will be determined according to RECIST 2.0 criteria, following imaging (CT/MRI) conducted throughout the study, on all enrolled participants across the Lutathera Therapy and Best Supportive Care arm. Tumour size according to RECIST 2.0 criteria will be examined with an anticipated decrease in tumour size should the study intervention be successful.
    Reduction in urinary 5-HIAA levels
    Reduction in urinary 5-HIAA levels throughout the course of the study will be compared across the Lutathera Therapy and Best Supportive Care arms. Elevated 5-HIAA levels are an indicator of Carcinoid Syndrome, which is the condition under study in this clinical trial. A reduction in urinary 5-HIAA levels is expected should the study intervention prove successful.
    Change in quality of life measurements (European Organization for Research and Treatment of Cancer questionnaires, QLQ-C30 and QLQ-GI.NET2)
    All enrolled patients will be required to complete the following validated quality of life questionnaires: - European Organization for Research and Treatment of Cancer questionnaires, QLQ-C30 and QLQ-GI.NET2 The change in quality of life scores will be compared across the Lutathera Therapy arm and Best Supportive Care arm. If the study intervention is successful in moderating disease, a positive increase in the quality of life scores is expected.

    Full Information

    First Posted
    July 5, 2019
    Last Updated
    August 3, 2020
    Sponsor
    King's College Hospital NHS Trust
    Collaborators
    Advanced Accelerator Applications
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04039516
    Brief Title
    Carcinoid Heart Disease and Peptide Receptor Radiotargetted Therapy
    Acronym
    CHARRT
    Official Title
    Phase II Randomised Trial to Assess Progression of Carcinoid Heart Disease in Patients Treated With Lutathera Therapy Compared to Best Supportive Care.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2020
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2020 (Anticipated)
    Primary Completion Date
    November 2024 (Anticipated)
    Study Completion Date
    December 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    King's College Hospital NHS Trust
    Collaborators
    Advanced Accelerator Applications

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Randomised trial to assess progression of carcinoid heart disease in patients treated with Lutathera therapy compared to best supportive care.
    Detailed Description
    This is an open-label, phase II, multicentre, randomised (1:1) clinical trial of an interventional medicinal product. This study will open at 3 centres across the UK. King's College Hospital NHS Foundation Trust will act as the coordinating centre for the study. In this study, treatment with Lutathera will be compared to treatment with current best supportive care (somatostatin analogues) in patients with inoperable, somatostatin receptor positive, histologically confirmed small bowel NENs and these patients should have stable disease according to RECIST criteria for a period of 6 months prior to study entry. Patients on the treatment arm will receive four administrations of 7.4 GBq (200 mCi) of Lutathera (and concomitant amino acids will be given with each administration for kidney protection). Patients are scheduled to continue to receive study treatment until any of the following occurs: Unacceptable toxicity; Progressive disease as determined by RECIST Criteria; Inability or unwillingness of the patient to comply with study procedures; Patient withdraws consent to participate Patients on the best supportive care arm will receive somatostatin analogue treatment every 4 weeks according to local standard of care practices. Tumour response in both arms will be assessed after cycles 2 and 4 of 177Lu-Dotatate therapy, or every 16 weeks for patients enrolled under the best supportive care arm, according to RECIST criteria. The study population is comprised of patients with stable carcinoid heart disease (CHD) and carcinoid syndrome. King's College Hospital performed surgery on 30 patients with carcinoid heart disease over the last 5 years. On review of patient records at King's, a further 30 patients with carcinoid heart disease were identified during the same time period who did not require surgery. Other centres participating in this study have similar populations of patients with CHD, with specific multi-disciplinary team meetings and outpatient clinics for identification and recruitment of suitable patients into the study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Carcinoid Heart Disease, Carcinoid Syndrome, Carcinoid Tumor

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Lutathera Treatment Arm
    Arm Type
    Experimental
    Arm Description
    • 4x cycles of 7.4 GBq (200mCi) of Lutathera therapy (177Lu-DOTA0-Tyr3-Octreotate) with concomitant amino acids for participants randomised onto the Lutathera therapy arm, every 8 weeks, plus long term somatostatin analogues (SSTA).
    Arm Title
    Best Supportive Care
    Arm Type
    No Intervention
    Arm Description
    Somatostatin analogue treatment according to current standard, routine care
    Intervention Type
    Drug
    Intervention Name(s)
    Lutathera
    Intervention Description
    A total of 4 infusions of Lutathera to be administered every 8 weeks.
    Primary Outcome Measure Information:
    Title
    The rate of progression of moderate carcinoid heart disease (CHD)
    Description
    The rate of progression of carcinoid heart disease (CHD) in patients with moderate CHD will be compared across the Lutathera Therapy and Best Supportive Care Arms and will be assessed through RECIST CT/MRI imaging and urinary 5-HIAA levels throughout the duration of the study. The rate of progression will be assessed at each study visit across both arms during the intervention and follow-up phase. If the study treatment is successful in delaying the rate of progression, then the rate of progression in the Lutathera (study intervention) arm is expected to be much slower than in the Best Supportive Care arm.
    Time Frame
    5 years
    Secondary Outcome Measure Information:
    Title
    Change in NYHA heart failure score
    Description
    The association between Lutathera Therapy against Best Supportive Care will be assessed by comparing the change in NYHA heart failure score in patients enrolled in both study arms. The NYHA Heart Failure Score is grade I to IV, with Grade I being No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath) and Grade IV being Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. The change in grade will be assessed with an anticipated reduction in grade if the study treatment is successful in reducing symptoms.
    Time Frame
    5 years
    Title
    Progressive disease
    Description
    Progressive disease will be determined according to RECIST 2.0 criteria, following imaging (CT/MRI) conducted throughout the study, on all enrolled participants across the Lutathera Therapy and Best Supportive Care arm. Tumour size according to RECIST 2.0 criteria will be examined with an anticipated decrease in tumour size should the study intervention be successful.
    Time Frame
    5 years
    Title
    Reduction in urinary 5-HIAA levels
    Description
    Reduction in urinary 5-HIAA levels throughout the course of the study will be compared across the Lutathera Therapy and Best Supportive Care arms. Elevated 5-HIAA levels are an indicator of Carcinoid Syndrome, which is the condition under study in this clinical trial. A reduction in urinary 5-HIAA levels is expected should the study intervention prove successful.
    Time Frame
    5 years
    Title
    Change in quality of life measurements (European Organization for Research and Treatment of Cancer questionnaires, QLQ-C30 and QLQ-GI.NET2)
    Description
    All enrolled patients will be required to complete the following validated quality of life questionnaires: - European Organization for Research and Treatment of Cancer questionnaires, QLQ-C30 and QLQ-GI.NET2 The change in quality of life scores will be compared across the Lutathera Therapy arm and Best Supportive Care arm. If the study intervention is successful in moderating disease, a positive increase in the quality of life scores is expected.
    Time Frame
    5 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Echocardiographic evidence of mild/ moderate carcinoid heart disease. Carcinoid syndrome with Echocardiographic evidence of carcinoid heart disease- to be defined further Elevated urinary 5-HIAA or NYHA class I or II on therapy [not necessarily exceeding label dose of SSA LAR; eg, could be 30mg SMS LAR plus sc SMS for breakthrough] Presence of metastasized or locally advanced, inoperable (curative intent) histologically proven, Grade 1 or Grade 2 gastroenteropancreatic neuroendocrine (GEP-NET) or Lung-NET tumor Age >18 Ki67 index ≤ 20% Patients who have provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related activities Confirmed presence of somatostatin receptors on all target lesions documented by CT/MRI scans, within 8 weeks prior to randomization (centrally confirmed), as assessed by the following somatostatin receptor imaging (SRI) modalities: [68Ga]-DOTA-TOC (Somakit-TOC™) PET/CT imaging or [68Ga]-DOTA-TATE PET/CT imaging (NETSPOTTM) or Somatostatin Receptor scintigraphy (SRS) with 111In-pentetreotide (Octreoscan®). 10. Irresectable disease 11. Karnofsky Performance Score (KPS) ≥60. Exclusion Criteria: Patients with progressive disease by RECIST progressed within 6 months Unable to consent Pregnant Chemotherapy within 3 months PRRT within 3 years Grade 3 tumours (WHO 2010) Severe or Uncontrolled carcinoid heart disease Renal impairment with eGRF <40 ml/min NYHA class III,IV

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    No IPD to be shared with other researchers.

    Learn more about this trial

    Carcinoid Heart Disease and Peptide Receptor Radiotargetted Therapy

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