Table 2.
Ongoing clinical trials assessing [177Lu]Lu-DOTATATE RLT in “Lutathera® Orphans”. The short title shown in the table; to facilitate any consultation, this is the original title entered by the experimenters on the site and not modified, even where not formally correct.
| S/E | NCT Number and Brief Title | Phase | Country | Conditions | Aim of Study | Orphan Condition |
|---|---|---|---|---|---|---|
| October 2021 / September 2029 |
NCT04954820 [102] Assessment of the Schema of Retreatment With Lutathera® in Patients With New Progression of Intestinal Well- differenciated NET. |
Phase II | France | NET; intestinal well differentiated endocrine tumor; progressive disease. | To evaluate the efficacy of 2 additional cycles of Lutathera® vs. active surveillance in patients already retreated with two cycles Lutathera® for a new progression of intestinal NET. | Retreatment |
| April 2022 / December 2025 |
NCT05178693 Lutathera and ASTX727 in Neuroendocrine Tumours. |
Phase I | United Kingdom |
NETs G1 or G2 or G3 | To determine whether pretreatment with ASTX727 before Lutathera® results in re-expression of SSTR2 in patients with metastatic NETs. | NET G3 |
| April 2023 / July 2024 |
NCT05687123 Testing the Addition of Sunitinib Malate to Lutetium Lu 177 Dotatate (Lutathera) in Pancreatic Neuroendocrine Tumors. |
Phase I | United States of America | PAN-NET of any grade | To test the safety, side effects, and best dose of sunitinib malate in combination with Lutathera® in treating patients with PanNETs. | NET G3 |
| January 2020 / July 2027 |
NCT03972488 Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET. |
Phase III | International | GEP-NET | To compare Lutathera® plus long-acting octreotide vs. high dose long-acting octreotide as first line treatment in G2 and G3 GEP-NET. | NET G3 |
| June 2020 / September 2024 |
NCT04525638 A Clinical Study to Assess the Combination of Two Drugs (177Lu-DOTATATE and Nivolumab) in Neuroendocrine Tumours. |
Phase II | Spain | NETNEC | To evaluate the efficacy and safety of [177Lu]Lu-DOTATATE in combination with nivolumab in adult patients with G3 NETs or NECs. | NET G3 and NEC |
| March 2022 / March 2028 |
NCT05247905 Comparing Capecitabine and Temozolomide in Combination to Lutetium Lu 177 Dotatate in Patients With Advanced Pancreatic Neuroendocrine Tumors. |
Phase II | United States of America | PAN-NET G1 or G2 or G3 |
To find out whether capecitabine and temozolomide or [177Lu]Lu-DOTATATE may kill more tumor cells in patients treated for metastatics or unresectable PanNETs. | NET G3 |
| August 2018 / December 2025 |
NCT03457948 Pembrolizumab With Liver-Directed or Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors and Liver Metastases. |
Phase II | United States of America | NET G1 or G2 or G3 of any primary site, including unknown primary site | To study the effectiveness of pembrolizumab and liver-directed therapy or Lutathera® in treatment of patients with symptomatic and/or progressive NETs with liver metastases. | NET G3—NET of any, primary origin, including CUP-NETs |
| November 2022 / November 2027 |
NCT05278208 Lutathera for Treatment of Recurrent or Progressive High- Grade CNS Tumors or Meningiomas Expressing SST2A. |
Phase I e II | United States of America | High-grade CNS primary central nervous system neoplasm; meningioma; | To evaluate safety and efficacy of Lutathera® in pediatric and young adult patients with progressive or recurrent high-grade CNS tumors and meningiomas (any grade) that express SSTR2. | Meningiomas and other tumors overexpressing SSTR— pediatric patiens |
| August 2022 / August 2028 |
NCT04711135 Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs. |
Phase II | International | GEP-NET G1 or G2 PPGLs |
To evaluate safety and dosimetry of Lutathera® in adolescent patients with SSTRs positive GEP-NETs and PPGLs. | PPGLs—pediatric patiens |
| August 2020 / June 2021 |
NCT03923257 Withdrawn, competing clinical trial opening Dosimetry Guided PRRT With 177Lu-DOTATATE in Children and Adolescents. |
Phase I e II | United States of America | NET PPGLs |
Assess Lutathera® in children and adolescents with neuroendocrine tumors and PHEO or PGL. | PPGLs—pediatric patiens |
| January 2023 / January 2025 |
NCT03966651 A Clinical Study Evaluating the Safety of Peptide Receptor Radionuclide Therapy (PRRT) With 177Lu-DOTA0-Tyr3- Octreotate in Children With Refractory or Recurrent Neuroblastoma Expressing Somatostatin Receptors. |
Phase I | France | Neuroblastoma | To define the Maximum Tolerated Dose (MTD) of [177Lu]Lu-DOTATATE in children with refractory or recurrent neuroblastoma. | Neuroblastoma—Pediatric patiens |
| July 2014 / December 2023 |
NCT02236910 [108] An Open Label Registry Study of Lutetium-177 (DOTA0, TYR3) Octreotate (Lu-DOTA-TATE) Treatment in Patients With Somatostatin Receptor Positive Tumours. |
Phase II | Canada | NET any primary origin (male or female ≥ 14–90 years of Age) |
To assess the efficacy (PFS and OS), safety and quality of life of patients treated with [177Lu]Lu-DOTATATE. | Pediatric patiens—NET of any primary origin |
| April 2014 / December 2033 |
NCT01876771 A Trial to Assess the Safety and Effectiveness of Lutetium-177 Octreotate Therapy in Neuroendocrine Tumours. |
Phase II | Canada | NET any primary origin (male or female ≥ 14–90 years of age) |
To assess efficacy and safety of [177Lu]Lu-DOTATATE treatment in patients with SSTR positive tumors and the assess the effect on quality of life and survival. | Pediatric patiens—NET of any primary origin |
| May 2021 / May 2031 |
NCT04903899 [109] 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-risk Neuroblastoma |
Phase II | Sweden | Neuroblastoma | Assess an intensified dosing schedule to deliver 2 doses over a 2-week period in neuroblastoma | Neuroblastoma—Pediatric patiens |
| May 2019 / May 2025 |
NCT03971461 Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma. |
Phase II | United States of America | Meningioma | To evaluate the efficacy of Lutathera® in patients with progressive WHO I-III or residual high-risk SSTR-positive meningioma. | Meningiomas and other tumors overexpressing SSTR |
| December 2023 / October 2025 |
NCT04614766 A Clinical Trial Evaluating the Safety of Combining Lutathera(R) and Azedra(R) to Treat Mid-gut Neuroendocrine Tumors |
Phase I e II | United States of America | NET midgut G1 or G2 PPGLs |
To identify the best tolerated doses of Lutathera® and Azedra® when coadministered to treat NETs. | PPGLs |
| November 2017 / Augus 2020 |
NCT03325816 [110] Nivolumab and 177Lu-DOTA0-Tyr3-Octreotate for Patients With Extensive-Stage Small Cell Lung Cancer |
Phase I e II completed |
United States of America | Small cell lung cancer | To assess safety and tolerability of combined treatment with Lutathera® and nivolumab, in subjects with SCLC or advanced or inoperable lung NETs and also to determine if PD-L1 expression increases the chances of a response | Meningiomas and other tumors overexpressing SSTR |
| October 2020 / November 2024 |
NCT04039516 Carcinoid Heart Disease and Peptide Receptor Radiotargetted Therapy |
Phase II | United Kingdom | GEP-NET G1 or G2 or Lung NET/bronchial carcinoid |
To assess progression of carcinoid heart disease in patients treated with Lutathera® compared to best supportive care. | Bronchial carcinoid |
| September 2020 / September 2024 |
NCT04544098 Lutathera in People With Gastroenteropancreatic (GEP), Bronchial or Unknown Primary Neuroendocrine Tumors That Have Spread to the Liver |
Phase I | United States of America | GEP-NET or CUP- NET G1 or G2 or G3 typical or atypical lung/bronchial carcinoid |
To investigate intrahepatic arterial and intravenous infusion of Lutathera® in patients with liver-dominant metastatic GEP-NETs, bronchial NETs, or well-differentiated CUP-NETs. | NET G3—CUP-NETs—Bronchial carcinoid |
| March 2020 / September 2024 |
NCT04082520 Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy |
Phase II | United States of America | Meningioma | To assess Lutathera® in treating patients with unresectable meningioma or progressive meningioma after EBRT. | Meningiomas and other tumors overexpressing SSTR |
| September 2021 / July 2024 |
NCT04665739 Testing Lutetium Lu 177 Dotatate in Patients With Somatostatin Receptor Positive Advanced Bronchial Neuroendocrine Tumors. |
Phase II | United States of America | Bronchial carcinoid | To assess if Lutathera® is more effective than everolimus in shrinking or stabilizing advanced bronchial neuroendocrine tumors. | Bronchial carcinoid |
| June 2019 / September 2020 |
NCT04106843 Radioactive Drug (177Lu-DOTATATE) for the Treatment of Locally Advanced, Metastatic, or Unresectable Rare Endocrine Cancers |
Phase II withdrawn, no participants registered. |
United States of America | PPGLs, Parathyroid carcinoma, pituitary gland carcinoma; thyroid gland medullary carcinoma |
To assess effectiveness of Lutathera® in patients with infrequent locally advanced or unresectable or metastatic endocrine cancers. | PPGLs and meningiomas and other tumors overexpressing SSTR |
| May 2022 / June 2025 |
NCT05109728 A Dose Finding Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination With Standard of Care and in Recurrent Glioblastoma as a Single Agent. |
Phase I | France, Portugal, Spain, Switzerland | Glioblastoma | To establish the recommended dose of Lutathera® in combination with the standard of care or as single agent in three different groups of participants with glioblastoma. | Meningiomas and other tumors overexpressing SSTR |
| April 2020 / June 2023 |
NCT04375267 [111] 177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours. |
Phase I | Sweden | Advanced GEP-NETs (poor prognosis and Ki67 > 15%), thymomas, meningiomas, mesothelioma | Phase I study of Lutathera® in combination with the PARP-inhibitor olaparib for treatment of patients with SSTRs positive tumors. | Meningiomas and other tumors overexpressing SSTR |
| March 2020 / December 2022 |
NCT04385992 Neoadjuvant PRRT With 177Lu-DOTATATE Followed by Surgery for Resectable PanNET |
Phase II | Italy | PAN-NET | To evaluate safety and efficacy of neoadjuvant PRRT with [177Lu]Lu-DOTATATE followed by surgical resection for resectable nonfunctioning PanNETs at high risk of recurrence. | Neoadjuvant purpose |
| September 2022 / December 2022 |
NCT04529044 177Lu-DOTATATE for the Treatment of Stage IV or Recurrent Breast Cancer. |
Phase II | United States of America | Breast cancer | To investigate the efficacy of Lutathera® in treating patients with stage IV or recurrent breast cancer positive for SSTR2. | Meningiomas and other tumors overexpressing SSTR |
| October 2011 / November 2018 |
NCT01456078 [112] A Multicenter Study Evaluating Efficacy and Safety of 177Lu-DOTA-TATE Based on Kidney-Dosimetry in Patients With Disseminated Neuroendocrine Tumors. |
Phase II completed |
Sweden | NET Liver metastases |
To optimize and personalize [177Lu]Lu-DOTATATE treatment in patients with metastatic NETs by performing renal dosimetry and to determine the biological effective dose for renal toxicity. | NET of any primary origin |
| July 2022 / November 2024 |
NCT05142696 A Safety Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Extensive Stage Small Cell Lung Cancer (ES-SCLC) Patients in Combination With Carboplatin, Etoposide and Tislelizumab. |
Phase I | France, Spain | Small cell lung cancer | To establish a safe and well tolerated dose of Lutathera® in combination with carboplatin, etoposide, and tislelizumab in induction treatment and with tislelizumab in maintenance treatment in newly diagnosed patients with extensive stage SCLC. | Meningiomas and other tumors overexpressing SSTR |
| May 2021 / December 2035 |
NCT04949282 Spanish Series of Patients Treated With the Radionuclide Lutetium177 |
Observational study | Spain | NET of any primary origin; other tumors overexpressing SSTR |
To assess the state of art of Lutathera® treatment in Spain in terms of efficacy, tolerance, and safety in routine clinical practice in different types of tumors. | NET of any primary origin—meningiomas and other tumors overexpressing SSTR |
| January 2023 / June 2024 |
NCT05198479 Phase II 177Lu-DOTATATE Study in Metastatic NPC With a Safety Run-in |
Phase II | Singapore | Metastatic nasopharyngeal cancer | To assess 6-month PFS in metastatic SSTR positive NPC treated with Lutathera® after progression to 2 or more lines of therapy or exhausted standard therapy | Meningiomas and other tumors overexpressing SSTR |
| February 2023 / February 2025 |
NCT05583708 Phase II Study of Peptide Receptor Radionuclide Therapy in Combination With Immunotherapy for Patients With Merkel Cell Cancer. |
Phase II | United States of America | Merkel cell carcinoma | A single-arm study with safety run-in of RLT with Lutathera® in bombination with immunotherapy for patients with Merkel cell cancer. | Meningiomas and other tumors overexpressing SSTR |
| October 2017 / 1 January 2026 |
NCT03206060 Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/Paraganglioma. |
Phase II | United States of America | PHEO Paraganglioma |
To evaluate the safety and tolerability of Lutathera® in unresectable SSTR positive tumors. | PPGLs |
| November 2004 / January 2021 |
NCT04029428 Peptide Receptor Radionuclide Therapy in the Treatment of Advanced, Non-resectable and/or Symptomatic Tumors With SSTR Overexpression. |
Phase II | Poland | GEP-NET (G1, G2 and G3), bronchial–pulmonary carcinoids (BPCs atypical-AC or typical-TC), PPGLs, CUP-NET | To evaluate RLT with [90Y]Y-DOTATATE, [177Lu]Lu-DOTATATE, or combined. | PPGLs—bronchial carcinoids—CUP-NETs—NET G3 |
| May 2016 / May 2021 |
NCT03454763 Optimizing the Interval Between Cycles of PRRT With 177Lu-DOTATATE in sstr2 Positive Tumors. |
Phase II | Italy | NET of any primary origin; other tumors overexpressing SSTR |
To optimize the interval between cycles of PRRT with [177Lu]Lu-DOTATATE in SSTR2-positive tumors | NET of any primary-origin meningiomas and other tumors overexpressing SSTR |
| October 2010 / August 2015 |
NCT01237457 177Lutetium-DOTA-Octreotate Therapy in Somatostatin Receptor-Expressing Neuroendocrine Neoplasms. |
Phase II | United States of America | Pheochromocytoma; bronchial carcinoids; other tumors overexpressing SSTR |
This is a phase II treatment protocol offering [177Lu]Lu-DOTATATE therapy for SSTR positive cancers. | Bronchial carcinoids—meningiomas and other tumors overexpressing SSTR |
| December 2022 / December 2031 |
NCT05249114 Study of Cabozantinib With Lu-177 in Patients With Somatostatin Receptor 2 Positive Neuroendocrine Tumors. |
Phase I | United Stated of America | fore-, mid-, or hindgut, including pancreas, or those with an unknown primary | To establish the MTD of cabozantinib in combination with Lutathera® at a standard dose followed by continuation cabozantinib. | CUP-NETs |
| October 2020 / January 2024 |
NCT04261855 Targeted Therapy and Avelumab in Merkel Cell Carcinoma. |
Phase I and Phase II | Australia | Metastatic Merkel cell carcinoma | To evaluate the safety and anti-tumor activity of Lutathera® or EBRT in combination with avelumab in patients with mMCC. | Meningiomas and other tumors overexpressing SSTR |
| April 2016 / December 2026 |
NCT02754297 [105,113] Personalized PRRT of Neuroendocrine Tumors |
Phase II | Canada | NET of any primary origin | To Evaluate personalized patient-tailored [177Lu]Lu-DOTATATE RLT. | NET of any primary origin |
| August 2013 / February 2017 |
NCT01915485 Radiolabeled Molecules for Medullary Thyroid Cancer |
Phase IV | Brazil | Medullary thyroid cancer | To assess [177Lu]Lu-DOTATATE RLT in SSTR positive medullary Thyroid cancer. | Meningiomas and other tumors overexpressing SSTR |
AC = atypical carcinoid; ASTX727 = oral decitabine and cedazuridine; BPC = bronchial–pulmonary carcinoids; CNS = central nervous system; CUP-NET = neuroendocrine tumor—cancer of unknown primary; EBRT = external beam radiation therapy; Ga = gallium; GEP-NET = gastroenteropancreatic neuroendocrine tumor; Lu = lutetium; mMCC = metastatic Merkel cell carcinoma; MRI = magnetic resonance imaging; MTD = maximum tolerated dose; NEC = neuroendocrine carcinoma; NET = neuroendocrine tumor; NPC = nasopharyngeal cancer; PAN-NET and PanNET = pancreatic neuroendocrine tumor; PARP = poly-ADP ribose polymerase; PET = positron emission tomography; PFS = progression-free survival; PHEO = pheochromocytoma; PPGLs = pheochromocytomas and paragangliomas; PI= principal investigator; PRRT = peptide receptor radionuclide therapy; QoL = quality of life; RECIST = response evaluation criteria in solid tumors; RLT = radioligand therapy; S/E= start/end study; SCLC = small cell lung cancer; SSA = somatostatine analogue; SSTR = somatostatine receptor; TC = typical carcinoid.