Patients with neuro-endocrine tumors with liver metastases with an indication for treatment with lutetium-177-dotatate
Conditions
Interventions
Product Name: Lutathera
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: 177Lu-DOTA0-Tyr3-Octreotate
Other descriptive name: LUTETIUM(177
Sponsors
University Medical Center Utrecht
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients must have given written informed consent. - Female or male aged 18 years and over. - Inoperable histologically proven neuro-endocrine tumor with indication for 177Lu-dotatate at enrollment time. - Well-differentiated neuro-endocrine tumor with a Ki67-index = 20% and a mitotic count of = 20. - Confirmed presence of somatostatin receptors on target lesions, based on somatostatin receptor imaging. - Life expectancy of 6 months or longer. - Eastern Cooperative Oncology Group (ECOG) performance score 0-1. - Hepatic metastases with at least one lesion = 3 cm on cross sectional imaging in both the right and left liver lobe (i.e. left and right lobes are based on the hepatic arterial perfusion territory). - Presence of excessive liver metastases, defined as >25% tumor load. - Patients may or may not have extrahepatic metastases. - Patients must have clinical or radiological progressive disease. - Negative pregnancy test for women of childbearing potential. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Any previous radioembolization, chemoembolization, or bland embolization, at any time, or surgery or radiofrequency ablation (or other ablative therapies) within 12 weeks prior to randomization in the study. - Prior external beam radiation therapy to the liver. - Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks prior to randomization in the study. - Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 hours before and 24 hours after the administration of 177Lu-dotatate, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 4 weeks before the administration of 177Lu-dotatate, unless the tumor uptake on target lesions observed by imaging during continued Octreotide LAR treatment is higher than normal liver uptake. - Any unresolved toxicity greater than National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE version 4.03) grade 2 from previous anti-cancer therapy. - Serum bilirubin > Upper Limit of Normal (ULN), serum albumin <3.0 g/dL. - Glomerular filtration rate <50 ml/min. - Hb <5.5 mmol/L; leucocytes <3.0x109/L; platelets <100x109/L (at baseline; 75x109/L is sufficient for cycles 2-4). - Uncontrolled congestive heart failure (NYHA II, III, IV). - Uncontrolled diabetes mellitus. - Patients suffering from diseases with an increased chance of liver toxicity. - Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or depression. Patients who are declared incompetent. - Previous enrolment in the present study or previous treatment with 177Lu-dotatate. - Female patients who are not using an acceptable method of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal ligation) OR are less than 1 year postmenopausal or surgically sterile during their participation in this study (from the time they sign the consent form) to prevent pregnancy. - Male patients who are not surgically sterile or do not use an acceptable method of contraception during their participation in this study (from the time they sign the consent form) to prevent pregnancy in a partner. - Body weight over 150 kg. - Current spontaneous urinary incontinence. - Severe allergy for i.v. contrast (Visipaque®), used for CT evaluation and treatment angiography.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate if there is a difference in post-treatment tumor-to-non-tumor (T/N) activity concentration ratio on SPECT/CT between the intra-arterial treated liver lobe and the intravenous treated liver lobe.; Secondary Objective: To evaluate whether: - There is a difference in absolute values of mean tumor and healthy liver absorbed dose on post-treatment SPECT/CT between the intra-arterial treated liver lobe and the intravenous treated liver lobe? - There is a difference in post-treatment tumor response between the intra-arterial treated liver lobe and the intravenous treated liver lobe? - There is a dose-response relation between tumor absorbed dose and post-treatment tumor response? - There is toxicity and how toxicity is compared to historical controls? - There is sufficient uptake of 177Lu-dotatate in extrahepatic lesions? - There is sufficient uptake of 177Lu-dotatate in the contralateral lobe, compared to historical controls? - There is a difference in kidney uptake of 177Lu-dotate between the IA treated patients and historical controls? - There is a difference in T/N activity concentration ratio between different timepoints post-injection? ;Primary end point(s): To assess if there is a difference in post-treatment tumor-to-non-tumor (T/N) activity concentration ratio on SPECT/CT between the intra-arterial treated liver lobe and the intravenous treated liver lobe. The T/N activity concentration will be measured on SPECT/CT. For each liver lobe up to three tumors (i.e. all >3 cm) will be selected based on size (i.e. the largest lesions). The weighted average activity per voxel of these lesions will be divided by the normal liver tissue mean activity per voxel (i.e. a VOI with 3 cm diameter will be placed in the normal liver tissue) to calculate the T/N ratio. The T/N activity ratios of th | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Difference in absolute values of mean tumor and healthy liver absorbed dose (in Gy) on post-treatment SPECT/CT between the intra-arterial treated liver lobe and the intravenous treated liver lobe: Dosimetry will be performed to measure mean tumor and healthy liver absorbed dose. Dosimetry will be performed on post-treatment SPECT/CT, which is performed 24 hours after administration of 177Lu-dotatate. The absolute absorbed dose in the IA treated liver lobe will be compared to the IV treated lobe. - Difference in post-treatment tumor response between the intra-arterial treated liver lobe and the intravenous treated liver lobe: The tumors are measured on CT and scored according to the Southwest Oncology Group (SWOG) solid tumor response criteria, RECIST 1.1, and mRECIST criteria. Scoring systems will be applied on the patient and liver level, separately. Because the eventual maximal shrinkage of the tumors may take months after completion of the therapy, we added the tumor response class ‘minimal response (MR)’, pertaining to a decrease in summed squares of tumor diameter more than 25% but less than 50%. The SWOG criteria are defined as follows: Complete response (CR) - Complete disappearance of all measurable and evaluable disease. No new lesions. Partial response (PR) - At least one measurable lesion, = 50% decrease under baseline in the sum of the products of perpendicular diameters of all measurable lesions. No new lesions. Stable disease (SD) / no response - Does not qualify for CR, PR, or progression. Progression - 50% increase or an increase of 10 cm2 in the sum of products of all measurable lesions. OR clear worsening of evaluable disease, OR reappearance of any new lesion/site. - To assess if there is a dose-response relation between tumor absorbed dose and post-treatment tumor response: The tumor | — |
Countries
Netherlands
Contacts
Public ContactClinical Research Coordinator
University Medical Center Utrecht
Outcome results
None listed