TheranosticTrials.org

Clinical Trial · NCT06121271

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

Overview

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.

Sponsor

University College, London

Phase

Phase 2

Contacts

Martyn Caplin, Prof. (CONTACT)

m.caplin@ucl.ac.uk

020 3758 2000

ClinicalTrials.gov

NCT06121271

Drug / Compound

DOTATATE

Isotope(s):
Target(s):
  • SSTR2
Ligand Class: Peptides
Chelator: DOTA

Eligibility

Inclusion

  • oral
  • oral
  • 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.
  • intravaginal
  • KPS ≥60.
  • Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days prior to treatment initiation). NOTE: Participants are considered not of childbearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or they are postmenopausal. Inclusion Criteria for Subsequent Treatments1\. Both serum creatinine ≤150 μmol/L (≤1.7 mg/dL) and 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).2\. Haemoglobin concentration ≥5.0 mmol/L (≥8.0 g/dL); WBC ≥2 x109/L (≥2000/mm3); platelets ≥75 x109/L (≥75 x103/mm3).3\. Total bilirubin ≤3x ULN. 4. Serum albumin \>3.0 g/dL, or serum albumin ≤3.0 g/dL, but normal prothrombin time.5\. KPS ≥60.
  • 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.
  • injectable
  • 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:
  • 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.
  • transdermal
  • Presence of at least 1 measurable site of disease on cross-sectional imaging.
  • progestogen-only hormonal contraception associated with inhibition of ovulation
  • implantable • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomised partner • sexual abstinence
  • 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.
  • 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.

Exclusion

  • Patients with a history of brain metastases must have a head CT with contrast to document stable disease prior to enrolment in the trial.
  • Serum albumin \<3.0 g/dL unless prothrombin time is within the normal range.
  • 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).
  • Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the trial.
  • Patients who have participated in any therapeutic clinical trial/received any investigational agent within the last 30 days are excluded from participation in this trial.
  • Interferon, Everolimus (mTOR-inhibitors), or other systemic therapies within 4 weeks prior to enrolment in the trial.
  • Current spontaneous urinary incontinence.
  • Uncontrolled congestive heart failure (NYHA II, III, IV).
  • Pregnancy, planning a pregnancy or lactation.
  • Participants will not be eligible for trial participation if they meet any of the exclusion criteria, or will be discontinued at the discretion of the Investigator if they develop any of the exclusion criteria during the trial.Exclusion Criteria at Baseline
  • Unwilling or unlikely to comply with the requirements of the trial. Exclusion Criteria for Subsequent Treatments1\. Exclusion criteria for Baseline # 1, 2, 3, 4, and 10 apply to all subsequent treatments, when a relationship cannot be excluded with either trial drugs or the corresponding toxicity has not resolved.2\. In relation to renal function, participants are also excluded from further therapy in case of \>40% increase of serum creatinine over the baseline and with a concomitant decrease of \>40% in creatinine clearance as calculated according to the Cockroft-Gault method, eventually confirmed by measured creatinine clearance (or GFR), if a relationship may not be excluded and the corresponding toxicity has not resolved.3\. When such exclusion criteria events occur, the participant will postpone any subsequent trial treatment until resolution of the event (normalisation or return to baseline values). The participant remains in the trial and continues observation with the scheduled tumour and clinical assessments.4\. All other exclusion criteria for enrolment eligibility apply to all subsequent treatments.
  • Patient with known incompatibility to CT Scans with IV contrast due to allergic reaction or renal insufficiency. If such participants can be imaged without the use of CT contrast material (ie, can tolerate MRI scans), such participants would not be excluded.
  • Total bilirubin \>3x upper limit of normal (ULN).
  • Haemoglobin concentration \<5.0 mmol/L (\<8.0 g/dL); WBC \<2 x109/L (2000/mm3); platelets \<75 x109/L (75 x103/mm3).
  • Any surgery, radioembolization, chemoembolization, chemotherapy, and radiofrequency ablation within 12 weeks prior to enrolment in the trial.
  • 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).
  • Prior external beam radiation therapy to more than 25% of the bone marrow.
  • Uncontrolled diabetes mellitus as defined by a fasting blood glucose \>2x ULN.
  • Patients with hypersensitivity to Lutathera (active substance or any of the excipients).
  • Involved in the planning or conduct of this trial.