Targeted Alpha-emitter Therapy of PRRT Naïve and Previous PRRT Neuroendocrine Tumor Patients (ALPHAMEDIX02)

A Phase 2 Open Label Study to Evaluate the Safety and Effectiveness of 212Pb-DOTAMTATE in Subjects With Somatostatin Receptor Expressing Neuroendocrine Tumors

Multicenter Phase 2 study of 212Pb-DOTAMTATE enrolling adult subjects with positive somatostatin positive neuroendocrine tumors with either no prior history of peptide receptor radionuclide therapy (PRRT naive) or prior history of peptide receptor radionuclide therapy (Previous PRRT)

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: AlphaMedix

Detailed Description

In this open-label, multicenter, single-arm Phase 2 study, adult subjects with histologically confirmed NETs and positive somatostatin analog imaging, with either no prior PRRT (PRRT naive) or prior history of peptide receptor radionuclide therapy (previous PRRT) will be enrolled to receive 212Pb-DOTAMTATE 67.6 μCi/kg dose per cycle

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Louisiana State University (LSU) Health Sciences Center - New Orleans
  • Texas
    • Houston, Texas, United States, 77042
      • Excel Diagnostics and Nuclear Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female ≥18 years old with unresectable or metastatic histologically confirmed NET
• Subjects must have received and progressed following somatostatin analog administration
• For PRRT naive subjects, documented progression of disease following previous therapy within 12 months prior to enrollment and the presence of at least 1 site of measurable disease per RECIST 1.1
• Subjects who previously received PRRT must have documented progression of disease and at least 1 site of measurable disease per RECIST 1.1 after receiving up to 4 doses (≤ 880 mCi) of 177Lu-DOTATATE/DOTATOC and received their last dose at least 6 months prior to Day 1

• Confirmed presence of somatostatin receptors on all lesions including the non-target and measurable lesions documented by CT/MRI scans, based on positive 68Ga-DOTATATE (NETSPOT®), 64Cu-DOTATATE (Detectnet™), or other Food and Drug Administration (FDA) approved SSTR PET/CT imaging within 6 weeks prior to enrollment. Follow up imaging should be performed with the same agent or modality used at baseline;

  1. Target lesions must be positive (greater than grade 2 uptake Krenning Score) or must have a standardized uptake value of more than the normal liver background.
  2. Lytic bone lesions, with an identifiable soft tissue component, evaluated by CT or MRI, can also be considered measurable lesions if the soft tissue component otherwise meets the definition of measurability according to RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) status 0-2;
• Life expectancy of at least 12 weeks in the opinion of the investigator at the time of screening;

• Sufficient bone marrow capacity and organ function in the recent blood tests within 3 weeks prior to Day 1, as defined by:

  1. White blood cell (WBC) ≥2,500/ mm3;
  2. Absolute neutrophil count (ANC) ≥1000/mm3;
  3. Platelets ≥100,000/mm3;
  4. Hemoglobin (HgB) ≥9.0 g/dL;
  5. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤3 X upper limit of normal (ULN);
  6. Total Bilirubin: ≤2 X ULN;
  7. Serum creatinine ≤1.7 mg/dL for PRRT naïve subjects; ≤ ULN for previous PRRT subjects;
  8. Serum albumin ≥3.0 g/L; if lower than 3.0 g/L requires normal range prothrombin time (PT) and international normalized ratio (INR), and
• Be willing to practice the following medically acceptable methods of birth control (both women of childbearing potential (WOCBP) and men who have partners of childbearing potential) from the Screening Visit through 3 months after the final administration 212Pb-DOTAMTATE

Exclusion Criteria:

• Prior whole-body radiotherapy or PRRT using 177Lu/90Y/111In-DOTATATE/ DOTATOC or Targeted Alpha Therapy (TAT).
• For subjects who previously received PRRT, prior treatment with: Prior treatment with 90Y- DOTATATE/ DOTATOC, 225Ac-DOTATATE/DOTATOC, and/or 111In-DOTATATE/ DOTATOC
• Prior regional hepatic radionuclide therapy within 4 months prior to enrollment or prior nonradioactive regional hepatic therapy within 6 months prior to enrollment.
• Known hypersensitivity to somatostatin analogues, Amino Acid infusion, or 212Pb-DOTAMTATE;
• Therapeutic use of any somatostatin analogue, including Sandostatin® LAR (within 28 days) and Sandostatin® (within 1 day) prior to Cycle 1 Day 1;
• History of myelodysplastic syndrome (MDS);
• Female subjects who are pregnant or lactating;
• Indication for surgical lesion removal with curative potential;
• Known brain metastases, unless these metastases have been treated and/or stable for 6 months prior to enrollment;
• Experimental cancer treatments or other investigational therapies within 6 weeks or five half-lives of the investigational medication prior to Day 1;
• Uncontrolled congestive heart failure (NYHA II, III, IV);
• Uncontrolled diabetes mellitus as defined by a hemoglobin A1C >10.0;
• Evidence of renal obstruction based on Tc-99m DTPA or TER for MAG3 renal scintigraphy or renal ultrasound.
• Known or active human immunodeficiency virus (HIV) or hepatitis B or C virus unless cured;
• Known or suspected active drug or alcohol abuse;
• Participation in other interventional clinical studies within 30 days prior to Day 1;
• Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years;
• Any somatic or psychiatric disease/condition or abnormal laboratory test that in the opinion of the investigator, may interfere with the objectives and assessments of the study; or
• Unable to comply with the requirements of the study protocol or be unsuitable for the study for any reason, in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pb212-DOTAMTATE; investigational radiotherapeutic drug targeting somatostatin receptor-positive neuroendocrine tumors in PRRT naive patients (Cohort 1) and previous PRRT patients (Cohort 2)	Drug: AlphaMedix; 212Pb-DOTAMTATE is a radiolabeled derivative of octreotide targeting somatostatin positive neuroendocrine tumors; Other Names: Pb212-octreotide analog

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.	The morphological imaging (CT/MRI) will be done before therapy and selected time points before therapy cycle to determine changes in the size of target lesions.	24 months after last dose administration
Number of patients with treatment-related adverse events as assessed by CTCAE v.4.0	To assess the safety and tolerability of 212Pb-DOTAMTATE	24 months after last dose administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the Median Progression free survival (mPFS)	PFS will be defined as the number of days from the first dose of 212Pb-DOTAMTATE to documented tumor progression per RECIST 1.1 criteria or death due to any cause.	24 months after last dose administration
Measurement of Overall Survival (OS)	OS will be defined as the number of days from the first dose of 212Pb-DOTAMTATE to the date of death due to any cause or the date of last contact (censored observations) at the data cut-off date.	24 months after last dose administration
Measurement of Time to Tumor Progression (TTP)	This measurement will determine the time from start of treatment with 212Pb- DOTAMTATE until disease progression.	24 months after last dose administration
To evaluate health-related quality of life (HRQL) using ECOG performance status	Changes in quality of life will be assessed relative to baseline. Eastern Cooperative Oncology Group (ECOG) is designed to measure how cancer affects subject's daily life and is assessed using 0-5 scale.	24 months after last dose administration
To evaluate health-related quality of life (HRQL) using HRQL questionnaire EORTC QLQ-C30	Changes in quality of life will be assessed relative to baseline. European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is a self-assessed questionnaire that consists of 30 questions designed to measure varying types of functioning, symptoms and overall health/quality of life. It is assessed using either a 4-point scale or 7-point scale, depending on the question.	24 months after last dose administration
To evaluate health-related quality of life (HRQL) using HRQL questionnaire EORTC QLQ-G.I.NET21	Changes in quality of life will be assessed relative to baseline. European Organisation for Research and Treatment of Cancer (EORTC) QLQ-G.I.NET21 is a self-assessed questionnaire that consists of 51 questions designed to assess symptoms or problems. It is assessed using a 4-point scale.	24 months after last dose administration

Collaborators and Investigators

• Sponsor: Orano Med LLC
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2021
• Primary Completion (Actual): April 14, 2025
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: November 4, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 10, 2021

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: neuroendocrine tumors; Pb212-DOTAMTATE; alpha-emitter-therapy
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: Alphamedix-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No