Carcinoid Heart DiseasePhase 2CHARRTNCT04039516
Carcinoid Heart Disease and Peptide Receptor Radiotargetted Therapy
A Phase 2 study testing Lutathera in people with Carcinoid Heart Disease and Carcinoid Syndrome, run by King's College Hospital NHS Trust.
Trial summary
Randomised trial to assess progression of carcinoid heart disease in patients treated with Lutathera therapy compared to best supportive care. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoid Heart Disease, Carcinoid Syndrome, Carcinoid Tumor
- What is being tested?
- Lutathera
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Oct 2020to Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
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- 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.
Who cannot join
- 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)
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- Severe or Uncontrolled carcinoid heart disease
- Renal impairment with eGRF <40 ml/min
- NYHA class III,IV
About this study
Official title: Phase II Randomised Trial to Assess Progression of Carcinoid Heart Disease in Patients Treated With Lutathera Therapy Compared to Best Supportive Care.
Randomised trial to assess progression of carcinoid heart disease in patients treated with Lutathera therapy compared to best supportive care.
Read the 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.
- Conditions
- Carcinoid Heart Disease, Carcinoid Syndrome, Carcinoid Tumor
- Being tested
- Lutathera
- Medical subject headings
- Carcinoid Heart Disease, Serotonin Syndrome, Carcinoid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LutatheraDrug
A total of 4 infusions of Lutathera to be administered every 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Lutathera Treatment Arm | Experimental | • 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). Receives: Drug: Lutathera |
| Best Supportive Care | No intervention | Somatostatin analogue treatment according to current standard, routine care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 years
Secondary outcomes (4)
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.
Measured: 5 years
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.
Measured: 5 years
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.
Measured: 5 years
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.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2019
- Study startOct 2020 (estimated)
- Primary completionNov 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoid Heart DiseaseStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Advanced Accelerator Applications
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04039516
- Sponsor's protocol ID
- 263064
- Acronym
- CHARRT
- Status last verified
- Aug 2020
- First submitted
- 5 Jul 2019
- Last updated
- 4 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No IPD to be shared with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomised Trial to Assess Progression of Carcinoid Heart Disease in Patients Treated With Lutathera Therapy Compared to Best Supportive Care.
- ClinicalTrials.gov ID
- NCT04039516
- Acronym / sponsor ID
- CHARRT / 263064
- Conditions
- Carcinoid Heart Disease, Carcinoid Syndrome, Carcinoid Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Collaborators
- Advanced Accelerator Applications
- Study start
- Oct 2020 (estimated)
- Primary completion
- Nov 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 31 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lutathera Treatment Arm | Experimental | Drug: Lutathera• 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). |
| Best Supportive Care | No intervention | –Somatostatin analogue treatment according to current standard, routine care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (9 listed)
- Patients with progressive disease by RECIST progressed within 6 months
- Unable to consent
- Pregnant
- Chemotherapy within 3 months
- PRRT within 3 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LutatheraA total of 4 infusions of Lutathera to be administered every 8 weeks. | Drug | Lutathera Treatment Arm |
Primary outcome
The rate of progression of moderate carcinoid heart disease (CHD)
Time frame: 5 years
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.
4 secondary outcomes
Change in NYHA heart failure score
Time frame: 5 years
Progressive disease
Time frame: 5 years
Reduction in urinary 5-HIAA levels
Time frame: 5 years
Change in quality of life measurements (European Organization for Research and Treatment of Cancer questionnaires, QLQ-C30 and QLQ-GI.NET2)
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2020.
- Individual participant dataSharing planned: No. No IPD to be shared with other researchers.
Related trials for Carcinoid Heart Disease
Active, not recruitingPhase 3
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Investigation of a Transcatheter Tricuspid Valved Stent Graft in Patients With Carcinoid Heart Disease
Tricuspid Regurgitation, Tricuspid Valve Disease
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CardioNETPOL National Registry of Carcinoid Heart Disease
Carcinoid Heart Disease, Neuroendocrine Tumors
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Development and Progression of Carcinoid Heart Disease in a Cohort of Adult Patients With Neuroendocrine Tumors
Carcinoid Heart Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lutathera in people with Carcinoid Heart Disease and Carcinoid Syndrome, run by King's College Hospital NHS Trust.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The rate of progression of moderate carcinoid heart disease (CHD) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2020.