Radiometabolic Therapy (RMT) With 177Lu PSMA in PSMA PET/CT Positive Advanced/Metastatic Tumours: a Basket Trial
Overview
- Phase
- Phase 2
- Intervention
- [177Lu]Lu-PSMA I&T
- Conditions
- Cancer
- Sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Enrollment
- 83
- Locations
- 2
- Primary Endpoint
- Acute toxicity rate
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
Phase 2 study, single arm trial enrolling patients with a Gallium-68/Fluorine-18 prostate-specific membrane antigen (PSMA) positive positron emission tomography/Computed Tomography (PET/CT) in order to be treated with Lutetium-177 (177Lu) PSMA.
Patients without risk factors for toxicity will receive 7.4 GBq of 177Lu-PSMA while patients with at least 1 risk factor for toxicity will receive 5.5 GBq of 177Lu-PSMA. Patients will receive 4 cycles every 8 weeks (+- 2 weeks)
Detailed Description
Since PSMA radioligand therapy (PSMA-RLT) demonstrated remarkable therapeutic efficacy in prostate cancer patients, the question arises whether PSMA-RLT could also achieve beneficial effects in other cancers expressing PSMA on the tumors cells themselves, or in the tumor-associated neovasculature. Expression of PSMA was early-on also identified in kidney, salivary glands, the duodenum and the central and peripheral nervous system. Subsequently, a wide variety of immunohistochemistry (IHC) studies showed PSMA to be upregulated on the endothelial cells of the neovasculature of a wide variety of other solid tumors where it may facilitate endothelial cell sprouting and invasion through its regulation of lytic proteases that have the ability to cleave the extracellular matrix. Similar to the introduction of PSMA-targeting theranostics in prostate carcinoma, overexpression of PSMA on newly formed tumor vessels may serve as a target for imaging and subsequent treatment of cancer through the use of agents that are capable of blocking PSMA in its function or through PSMA-mediated delivery of chemotherapeutics or radiation agents. Preclinical data suggests that PSMA might be involved in cancer-related angiogenesis by degrading the extracellular matrix and participating in integrin signal transduction.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically or cytologically confirmed advanced/metastatic solid tumors; any other tumor types documented as PSMA-positive that may benefit from receptor radionuclide therapy and for which there aren't any other effective treatments. For cerebral PSMA-positive tumors, if biopsy is no feasible for technical reasons or risk benefit balance, patients may be enrolled if CT or MRI strongly suggest oncological lesion confirming the 18F- and/or 68Ga PET-CT PSMA positivity;
- •Patients must have measurable disease; patients with prostate cancer who have only bone lesions can be enrolled. See section 9.2 and Appendix D for the evaluation of measurable disease;
- •Relapse or progression of disease on CT/MRI scan and/or WBD-MRI;
- •For patients with prostate cancer: documented radiological progression (in soft tissue and / or bone) and/or biochemical progression (sequence of PSA rising values from a minimal starting value ≥ 1 ng/ml) according to PCWG3;
- •Patients will be admitted to therapeutic phase only if the diagnostic PET/CT PSMA SUV max is ≥ 3;
- •No therapeutic alternatives;
- •Male or Female, aged ≥ 18 years;
- •Life expectancy of greater than 12 weeks;
- •ECOG performance status ≤ 2 (see Appendix A);
- •Patients must have normal organ and marrow function as defined below:
Exclusion Criteria
- Not provided
Arms & Interventions
[177Lu]Lu-PSMA I&T
\[177Lu\]Lu-PSMA I\&T, intravenous, dosage of 5.5 - 7.4 GBq every 8 weeks
Intervention: [177Lu]Lu-PSMA I&T
Outcomes
Primary Outcomes
Acute toxicity rate
Time Frame: 40 months
safety is evaluated according to version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE). Safety is defined as the percentage of patients who experience acute toxicity grade3/grade4 from the 1st treatment until 30 days after the last treatment cycle.
disease control rate (DCR)
Time Frame: 40 months
is DCR, defined as the percentage of patients who have achieved complete response, partial response, stable disease (according to RECIST 1.1) or no progression of disease for prostate cancer (according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria) at the 1st planned evaluation
Secondary Outcomes
- progression-free survival (PFS)(68 months)
- overall survival (OS)(68 months)
- late toxicity(68 months)
- PET/CT response(68 months)