Trial of Lu-177 DOTATATE (Lutathera®) in Unlicensed Indications

NCT06121271 | Not Yet Recruiting Phase 2

• 1 other identifier: 139005
• Study Type: interventional
• Target: 110
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a phase 2, open, single-site trial. The primary objective of this study is to prospectively evaluate the safety and efficacy in participants treated with Lu-177 DOTATATE (Lutathera) in unresectable or metastatic, somatostatin receptor-expressing neuroendocrine tumours (NET) in currently unlicensed indications (eg, bronchial and thymic NET; paraganglioma/phaeochromocytoma; medullary thyroid carcinoma; and those requiring repeat peptide receptor radionuclide therapy (PRRT) with 2 further cycles of Lutathera). The aim is to recruit a total of 75-110 participants. Each patient will receive 4 cycles of Lutathera with 8-12 weeks time interval (except patients requiring repeat PRRT will receive 2 further cycles of Lutathera). The follow-up period will be for 2 years from the date of the last treatment.

Conditions

Bronchial and Thymic Neuroendocrine Tumour; Paraganglioma/ Phaeochromocytoma; Medullary Thyroid Carcinoma; Those Requiring Repeat Peptide Receptor Radionuclide Therapy

Outcome Measures

Primary Outcomes (3)

• To prospectively evaluate safety in participants treated with Lu-177 DOTATATE (Lutathera) in somatostatin receptor-expressing neuroendocrine tumours (NET) in currently unlicensed indications

  Treatment-related toxicity will be assessed in all participants by Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0. This will be done by performing electrocardiograms (ECGs), vital signs, and clinical laboratory tests (haematology, clinical chemistry, or urinalysis)at the baseline and before and after every treatment and during the follow-up period.

  4 years

• To prospectively evaluate tolerability in participants treated with Lu-177 DOTATATE (Lutathera) in somatostatin receptor-expressing neuroendocrine tumours (NET) in currently unlicensed indications

  Treatment-related side effects and cancer-related symptoms will be assessed in all participants Questionnaire after every treatment and during the follow-up period.

  4 years

• To prospectively evaluate efficacy in participants treated with Lu-177 DOTATATE (Lutathera) in somatostatin receptor expressing neuroendocrine tumours (NET) in currently unlicensed indications

  The efficacy of Lu-177 DOTATATE is assessed in all participants by measuring Progression Free Survival (PFS) and defined as the time from the date of start of treatment the date of the first documented tumour progression or death due to any cause.

  4 years

Secondary Outcomes (2)

• • To determine the Objective Response Rate (ORR)

  2 years

• • To determine the Overall Survival (OS).

  4 years

Study Arms (4)

Bronchial and Thymic Neuroendocrine Tumour

EXPERIMENTAL

Drug: Lu-177 DOTATATE (Lutathera®)

Paraganglioma/ Phaeochromocytoma

EXPERIMENTAL

Drug: Lu-177 DOTATATE (Lutathera®)

Medullary Thyroid Carcinoma

EXPERIMENTAL

Drug: Lu-177 DOTATATE (Lutathera®)

Those Requiring Repeat Peptide Receptor Radionuclide Therapy

EXPERIMENTAL

Drug: Lu-177 DOTATATE (Lutathera®)

Interventions

Lu-177 DOTATATE (Lutathera®) DRUG

Treatment with Lutathera will consist of a total cumulative intravenous (IV) administered radioactivity dose of 29.6 GBq (800 mCi) or 14.8 GBq (400 mCi) for 4 cycles or 2 cycles of Lutathera, respectively.

Bronchial and Thymic Neuroendocrine Tumour; Medullary Thyroid Carcinoma; Paraganglioma/ Phaeochromocytoma; Those Requiring Repeat Peptide Receptor Radionuclide Therapy

Eligibility Criteria

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

You may qualify if:

• Patients ≥18 years of age.
• Participants capable of giving informed consent
• Presence of unresectable or metastatic, well differentiated, somatostatin receptor positive non gastroenteropancreatic neuroendocrine tumours. Or for those having 2 cycles repeat therapy, GEP NET \> 18 months from start of previous PRRT.
• Patients must have progressive disease based on RECIST Criteria, Version 1.1. In order to make the assessment, two CT (or MRI) scans are required. The oldest scan must not be older than 3 years from the date of enrolment. The most recent scan must not be older than 6 weeks from the date of enrolment.
• Confirmed presence of somatostatin receptors on all target lesions (for target/non-target/measurable lesions definition see RECIST Criteria, Version 1.1) documented by CT/MRI scans, based on positive OctreoScan or Ga68 Dotatate PET imaging within 24 weeks prior to enrolment in the trial.
• The tumour uptake observed in each target lesion (for target/non-target/measurable lesions definition see RECIST Criteria, Version 1.1) using OctreoScan/Tc-99m-SRS should be ≥ normal liver uptake observed on planar imaging.
• The tumour uptake observed in each target lesion (for target/non-target/ measurable lesions definition see RECIST Criteria, Version 1.1) using Ga68 Dotatate PET should be ≥ normal liver uptake observed on PET imaging.
• KPS ≥60.
• Presence of at least 1 measurable site of disease on cross-sectional imaging.
• Females of childbearing potential (defined as \<2 years after last menstruation and not surgically sterile) and males, who are not surgically sterile or with female partners of childbearing potential must be willing to use a highly effective method of contraception during treatment and for a minimum of 6 months after the end of treatment (hormonal or barrier method of birth control; abstinence). Contraceptive methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include:
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• oral
• intravaginal
• transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation

You may not qualify if:

• Either serum creatinine \>150 μmol/L (\>1.7 mg/dL), or calculated creatinine clearance \<40 mL/min, eventually confirmed by measured creatinine clearance (or measured GFR using isotopic GFR measurement) \<40 mL/min (the measured creatinine clearance/GFR is required only as confirmatory exam).
• Haemoglobin concentration \<5.0 mmol/L (\<8.0 g/dL); WBC \<2 x109/L (2000/mm3); platelets \<75 x109/L (75 x103/mm3).
• Total bilirubin \>3x upper limit of normal (ULN).
• Serum albumin \<3.0 g/dL unless prothrombin time is within the normal range.
• Pregnancy, planning a pregnancy or lactation.
• Any surgery, radioembolization, chemoembolization, chemotherapy, and radiofrequency ablation within 12 weeks prior to enrolment in the trial.
• Interferon, Everolimus (mTOR-inhibitors), or other systemic therapies within 4 weeks prior to enrolment in the trial.
• Patients with a history of brain metastases must have a head CT with contrast to document stable disease prior to enrolment in the trial.
• Uncontrolled congestive heart failure (NYHA II, III, IV).
• Uncontrolled diabetes mellitus as defined by a fasting blood glucose \>2x ULN.
• Any participant receiving treatment with short-acting Octreotide, which cannot be interrupted for 12 hours before and 24 hours after the administration of Lutathera, or any participant receiving treatment with Octreotide LAR or Lanreotide Autogel, which cannot be interrupted for at least 28 days before the administration of Lutathera, unless the tumour uptake observed on target and non-target but measurable lesions by OctreoScan or Ga68 Dotatate PET imaging during continued Octreotide LAR or Lanreotide Autogel treatment is at least as high as normal liver uptake observed by planar imaging (Kwekkeboom, Krenning et al. 2009).
• Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the trial.
• Prior external beam radiation therapy to more than 25% of the bone marrow.
• Current spontaneous urinary incontinence.
• Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.

Sponsors & Collaborators

• University College, London: lead

MeSH Terms

Conditions

Carcinoma, Medullary

Interventions

lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Martyn Caplin, Prof.

CONTACT

020 3758 2000; m.caplin@ucl.ac.uk

Study Design

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

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: November 7, 2023
• Study Start: December 18, 2023
• Primary Completion (Estimated): November 6, 2027
• Study Completion (Estimated): November 6, 2027
• Last Updated: December 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share