177Lu-DOTA-EB-TATE for Neuroendocrine Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Molecular Targeting Technologies, Inc.
Must not be taking: Somatostatin analogues
Disqualifiers: Pregnancy, Liver involvement, Bone marrow involvement, Infections, Diabetes, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This trial is testing a new targeted radiation therapy for patients with advanced or hard-to-remove GEP-NETs. The therapy uses a radioactive substance that binds to cancer cells and delivers radiation directly to them.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot use somatostatin or its analogues within 4 months of the treatment, and short-acting octreotide must be stopped 24 hours before and after the treatment.
What data supports the effectiveness of the treatment 177Lu-DOTA-EB-TATE for neuroendocrine cancer?
Is 177Lu-DOTA-EB-TATE safe for humans?
What makes the drug 177Lu-DOTA-EB-TATE unique for treating neuroendocrine cancer?
Eligibility Criteria
Adults over 18 with advanced, inoperable well-differentiated neuroendocrine tumors (GEP-NETs) that are positive for somatostatin receptors can join this trial. They must have measurable disease, agree to use contraception, and have not had certain recent treatments or other cancers. People with severe organ dysfunction, active infections like hepatitis or HIV, uncontrolled diabetes, or who are pregnant/breastfeeding cannot participate.Inclusion Criteria
I had local therapy over 4 weeks ago.
My last surgery was more than 6 weeks ago.
Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation, including follow-up (7 months after the last dose of study drug for women and 4 months for men)
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Exclusion Criteria
I haven't used somatostatin or its analogues in the last 4 months.
I have tumors that cannot be treated with local therapies before starting the treatment.
I have no other cancers except for possibly non-melanoma skin cancer or treated cervical carcinoma in situ.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a single-dose intravenous administration of 177Lu-DOTA-EB-TATE per 6-week cycle, for a total of 2 cycles, with dose escalation from 50 mCi to 150 mCi
12 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- 177Lu-DOTA-EB-TATE (Radioisotope Therapy)
Trial OverviewThe trial is testing the safety and dosage of a new treatment called 177Lu-DOTA-EB-TATE in patients with specific types of neuroendocrine tumors. It's an early-phase study focusing on how well patients tolerate the drug and how it distributes in their bodies.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Peptide Receptor Radionucleotide Therapy (PRRT)Experimental Treatment2 Interventions
The treatment regimen will consist of a single-dose intravenous administration of 177Lu-DOTA-EB-TATE per 6-week cycle, for a total of 2 cycles. The dose per cycle will be fixed for each patient and will be escalated in 3 different dose levels, from 50 mCi to 150 mCi (1.85 -5.55 GBq). Each dose of 177Lu-DOTA-EB-TATE will be administered in association with intravenous renal protective amino acid solutions.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Cancer CenterNew York, NY
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Who Is Running the Clinical Trial?
Molecular Targeting Technologies, Inc.Lead Sponsor
ClinSmartIndustry Sponsor
References
[Treatment of Gastroenteropancreatic Neuroendocrine Tumors with 177Lu-DOTA-TATE: Experience of the Portuguese Institute of Oncology in Porto]. [2019]The purpose of this article is to report the experience of the Portuguese Institute of Oncology - Porto in the treatment of gastroenteropancreatic neuroendocrine tumors with 177Lu-DOTA-TATE, regarding the safety and efficacy of this treatment modality.
Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects. [2018]Label="INTRODUCTION" NlmCategory="BACKGROUND"> 177Lu-DOTA-TATE is a clinically useful and promising therapeutic radiopharmaceutical for peptide receptor radionuclide therapy of neuroendocrine tumors (NETs) overexpressing somatostatin receptors. Currently, the radiopharmaceutical is prepared in-house at nuclear medicine centers, thereby restricting its use to limited centers only. In this article, the authors describe systematic studies toward bulk scale formulation of "ready-to-use" 177Lu-DOTA-TATE using medium specific activity 177Lu (740-1110 GBq/mg) at a centralized radiopharmacy facility.
Response to Single Low-dose 177Lu-DOTA-EB-TATE Treatment in Patients with Advanced Neuroendocrine Neoplasm: A Prospective Pilot Study. [2019]Objective:177Lu-DOTA-EB-TATE is a theranostic agent based on octreotate that uses an Evans blue structure to bind albumin to improve the pharmacokinetics and pharmacodynamics. This pilot study aims to evaluate the efficacy of a single low-dose treatment using 177Lu-DOTA-EB-TATE in patients with advanced neuroendocrine neoplasm (NEN). Methods: With IRB approval and informed consent, 4 NEN patients were enrolled to undergo 177Lu-DOTA-EB-TATE treatment with a single low dose of 0.66 ± 0.06 GBq (17.8 ± 1.7 mCi); 3 other NEN patients were enrolled as controls to undergo 177Lu-DOTA-TATE treatment with administered activity of 3.98 ± 0.17 GBq (107.6 ± 4.6 mCi). One primary tumor and 62 metastatic lesions in the 7 patients were evaluated by 68Ga-DOTA-TATE PET/CT immediately before and one or three months after the treatment. Maximum SUV (SUVmax) of the tumors ≥2.0 cm in diameter were measured and percentage of change (ΔSUV) after treatment were calculated. Results: All 4 patients subjected to 177Lu-DOTA-EB-TATE treatment tolerated the administered activity without significant adverse effects and showed symptomatic remission. Among the patients, 40 tumors were found with diameter ≥2.0 cm, with the baseline SUVmax varied from 1.5-82.9 (35.9 ± 21.0) and the ΔSUVs before and three months after the treatment from -75.1-26.3% (-38.9 ± 25.5%). Twenty-nine (72.5%) of the tumors showed >15% decrease of SUVmax (ΔSUV = -75.1%--17.1%). There was a significant negative correlation between the baseline SUVmax and the ΔSUV after treatment (r = -0.852, P < 0.001). Compared with the control 177Lu-DOTA-TATE therapy, the 177Lu-DOTA-EB-TATE treatment using approximately 1/6 the dose showed no significant difference in ΔSUV (-7.9 ± 5.4% vs. -5.8 ± 3.9%, P = 0.189) as demonstrated by the tumors with comparable baseline SUVmax from 10.0-35.0. Conclusion: A single low-dose 177Lu-DOTA-EB-TATE treatment appears to be safe and effective in the treatment of NENs with high 68Ga-DOTA-TATE uptake. This pilot study merits further investigation with increased dose and frequency of 177Lu-DOTA-EB-TATE administration with potential advantages over 177Lu-DOTA-TATE.
Gastro-Enteric-Pancreatic Neuroendocrine Tumor Treatment: 177Lu-DOTATATE. [2023]177Lu-DOTA-TATE therapy is a highly effective therapy in metastatic, well-differentiated, somatostatin receptor-positive GEP-neuroendocrine tumors (NETs) with mostly tolerable adverse effects. Guidelines generally refer to peptide receptor radionuclide therapy as a second-line therapy after SSA in gastroenteric and second- or third-line therapy in pancreatic NETs to improve survival rates and quality of life. Although we do not have sufficient data, 177Lu-DOTA-TATE therapy may also have a role in high-grade NET therapy, mostly in combination with other treatments such as chemotherapy.
Safety and efficacy of peptide receptor radionuclide therapy with 177Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors. [2022]Rationale: This study aimed to assess the safety, efficacy, and survival of 177Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors (NETs). Methods: Thirty patients with metastatic NETs were prospectively enrolled and treated with 177Lu-DOTA-EB-TATE (3 intended cycles at 8 to 12-week intervals, 3.7 GBq/cycle). Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The treatment response was graded according to RECIST 1.1 and PERCIST 1.0 criteria. Kaplan-Meier analysis was performed to calculate progression-free survival (PFS) and overall survival (OS). Results: Patients tolerated therapy well without acute adverse effects. During peptide receptor radionuclide therapy (PRRT), no grade 4 toxicity was observed in any of the patients; grade 3 hematotoxicity was recorded in 4 patients, including grade 3 thrombocytopenia in 4 patients (13.3%) and grade-3 anemia in 1 patient (3.3%); grade 3 hepatotoxicity was recorded in 1 (3.3%) patient, and no grade 2/3/4 nephrotoxicity was observed. On long-term follow-up, none of the patients developed grade 4 hematotoxicity or nephrotoxicity of any grade, reversible grade 3 hematotoxicity (thrombocytopenia) occurred in 1 patient. There was no incidence of leukemia or myelodysplastic syndrome for the duration of follow-up. Of 27 patients with RECIST-measurable disease, partial response and stable disease were seen in 9 and 14 patients, respectively, resulting in a response rate of 33.3% and disease control rate of 85.2%. Of 29 patients evaluable for response on 68Ga-DOTATATE PET/CT, 14 had partial response and 11 had stable disease, with a response rate of 48.3% and disease control rate of 86.2%. The follow-up period ranged from 5 to 57 months after the first 177Lu-DOTA-EB-TATE PRRT with a median follow-up of 46 months. The median PFS was 36 months, and the median OS was not reached. Ki-67 index of greater than 10% was associated with poorer PFS (P = 0.012). Conclusions: Our results suggest that PRRT with approximately 3.7 GBq 177Lu-DOTA-EB-TATE has acceptable toxicity profile and is effective in treating metastatic NET with high disease control rate. In addition, 177Lu-DOTA-EB-TATE achieved a favorable survival outcome with encouraging PFS.
Manual on the proper use of lutetium-177-labeled somatostatin analogue (Lu-177-DOTA-TATE) injectable in radionuclide therapy (2nd ed.). [2018]Here we present the guideline for the treatment of neuroendocrine tumors using Lu-177-DOTA-TATE on the basis of radiation safety aspects in Japan. This guideline was prepared by a study supported by Ministry of Health, Labour, and Welfare, and approved by Japanese Society of Nuclear Medicine. Lu-177-DOTA-TATE treatment in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection shown in this guideline are considered internationally useful as well. Only the original Japanese version is the formal document.
Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">The use of lutetium-177 (177Lu)-based radiopharmaceuticals in peptide receptor nuclear therapy is increasing, but so is the number of nuclear medicine workers exposed to higher levels of radiation. In recent years, [177Lu]Lu-DOTA-TATE has begun to be widely used for the treatment of neuroendocrine tumours. However, there are few studies evaluating the occupational radiation exposure during its administration, and there are still some challenges that can result in higher doses to the staff, such as a lack of trained personnel or fully standardised procedures. In response, this study aims to provide a comprehensive analysis of occupational doses to the staff involved in the administration of [177Lu]Lu-DOTA-TATE.
Lutetium Lu-177 Dotatate Flare Reaction. [2022]Lutetium Lu-177 dotatate is the first peptide receptor radionuclide therapy approved by the US Food and Drug Administration. Well-designed studies in Europe have shown dramatic effectiveness in improving progression-free survival in patients with gastroenteropancreatic neuroendocrine tumors, which are progressive and generally metastatic. This therapy is a molecular targeted therapy linking a beta-emitting radioisotope to dotatate, which binds tightly to somatostatin receptors on neuroendocrine tumors cells. Various adverse effects of this therapy have been reported in the literature, including potential toxicity to renal, hepatic, and hematologic tissues and risk of second malignancy. Our study sought to explore acute adverse effects in this patient population.
68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model. [2017]Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68Ga/177Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68Ga/177Lu for 68Ga/177Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68Ga-DOTA-TATE or 177Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68Ga-DOTA-TATE and 177Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68Ga-DOTA-TATE and 177Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.
Dose escalation of an Evans blue-modified radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors. [2022]Label="PURPOSE">To evaluate the safety and efficacy of 177Lu-DOTA-EB-TATE, a radiolabeled somatostatin analog modified by Evans blue, at escalating doses, was used to increase tumor retention in patients with progressive metastatic neuroendocrine tumors (NETs).