Theranostics of Radiolabeled Somatostatin Antagonists 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11 in Patients With Neuroendocrine Tumors

Study Overview
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Brief Summary
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This study has 3 steps and not everyone will have all 3 steps done. The overall goals are to see if a new experimental drug is safe to image (step 1) and treat neuroendocrine tumors (step 2 and 3).

Official Title
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Theranostics of Radiolabeled Somatostatin Antagonists 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11 in Patients With Neuroendocrine Tumors

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Device: PET/CT Imaging
* Radiation: 68Ga-DOTA-JR11
* Radiation: 177Lu-DOTA-JR11


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and the willingness to sign a written informed consent document Adults ≥ 18 years old Histologically or cytologically confirmed metastatic and/or unresectable progressive, well differentiated carcinoid or pancreatic NET carcinoids Progressive metastatic disease defined by one of the following, occurring within 6 months of study entry: At least a 20% increase in radiologically or clinically measurable disease Appearance of any new lesion Symptomatic disease (including worsening hormonal symptoms or symptoms related to tumor burden) Measurable disease as defined by RECIST 1.1. At least one metastasis must show uptake of 111In-DTPA-octreotide on SPECT that is higher than the physiologic radiotracer uptake by the liver ECOG performance status ≤ 2 (Karnofsky ≥ 60%) Patients must have normal organ and marrow function as defined below: Leukocytes ≥ 3.0 x 109/L Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L Hemoglobin ≥ 9.0 g/dL Platelets ≥ 200 x 10^9/L Total bilirubin ≤ 1.25 x Upper Limit Normal (ULN) AST (SGOT)/ ALT(SGPT) ≤ 2.5 x ULN with liver metastases Alkaline phosphatase < 2 x ULN (if known liver or bone disease) Serum albumin > 30 g/L, or serum albumin = 30 g/L but normal prothrombin time Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) calculated CrCl ≥ 60 mL/min/1.73m^2 Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation Previous local therapy (e.g., chemoembolization or bland embolization) is allowed if completed > 6 weeks prior to study entry. For such patients, there must be either progression of measurable disease documented within the treatment field, or measurable progressive disease outside the treatment field prior to study entry. Previous chemotherapy and/or investigational agents are allowed if completed > 4 weeks prior to study entry (> 6 weeks if last regimen contained bis-chloroethyl nitrosourea (BCNU) or mitomycin C). For patients who received systemic therapy prior to study entry, there must be documented progression of measurable disease since receiving systemic therapy prior to study entry. Patients must not have disease that is currently amenable to surgery. Prior surgery is allowed no less than 6 weeks prior to study entry. Exclusion Criteria: History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-DOTA-JR11 as assessed from medical records Life expectancy < 6 months as assessed by the treating physician. Treatment with short-acting somatostatin analogs less than 3 days and Sandostatin® depot injection less than 5 weeks before scanning and treatment Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Women who are pregnant or breastfeeding Toxicities from prior therapies that have not resolved to grade 1 or grade 0 Known CNS metastases and/or carcinomatous meningitis Active malignancy of metastatic potential other than the known carcinoid or pancreatic NET within the past three years >20% bone marrow external beam radiotherapy and/or previous radioisotope therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11<br>Pts get a PET/CT study with approx.150-200 MBq of 68Ga-DOTA-JR11. Lesions with focal radiotracer uptake not explained by physiologic sstr2 expression will be interpreted as metastatic disease. If 68Ga-DOTA-JR11 uptake by metastases with a diameter of more than 2 cm is less than the physiologic radiotracer uptake by the liver, no further imaging & therapy will be performed as part of the study, as it is unlikely that pts with this low radiotracer uptake will benefit from PRRT (2). All other pts will undergo a dosimetric study with 1850 MBq (less than 100 μg peptide) of 177Lu-DOTA-JR11. Results of the dosimetry study, will determine the balance of activity of 177Lu-DOTA-JR11 that can be administered without exceeding the radiation dose limits. This activity will be split into 2 equal amounts to be delivered in 2 cycles, approximately 3 months apart. After each therapy cycle, pts will be followed clinically for 3 months. | Device: PET/CT Imaging<br> <br> Radiation: 68Ga-DOTA-JR11<br> <br> Radiation: 177Lu-DOTA-JR11<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | according to RECIST 1.1 and median progression-free and overall survival will be estimated and reported with 95% confidence intervals | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiolabeled Somatostatin Antagonists, 68Ga-DOTA-JR11, 177Lu-DOTA-JR11, Pet scan, CT scan, 15-161