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Radiometabolic Therapy With 177Lu PSMA in PSMA PET/CT Positive Advanced/Metastatic Tumours: (LUBASKET)

Primary Purpose

Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
[177Lu]Lu-PSMA I&T
Sponsored by
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer focused on measuring basket study, PSMA PET/CT positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 reason or risk benefit balance, patients may be enrolled if CT or MRI strongly suggest oncological lesion confirming the Gallium-68 PET-CT PSMA positivity. Patients must have measurable disease; for patients with prostate cancer, also patients with only bone lesions can be enrolled. Relapse or progression of disease on CT scan and / or MRI; For patients with prostate cancer: documented radiological progression (in soft tissue and / or bone) and / or biochemical progression (sequence of Prostate-Specific Antigen (PSA) rising values from a minimal starting value ≥ 1 ng/ml) according to PCWG3. Patients with documented disease will be admitted to therapeutic phase only if the semi quantitative intensity of lesions uptake at the diagnostic PET/CT PSMA is higher than that of salivary glands or SUV has to be 1.5 times higher than the average total body No therapeutic alternatives Male or Female, aged>18 years Life expectancy of greater than 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status <2 Patients must have normal organ and marrow function If female of childbearing potential highly effective birth control methods, according to guideline "Recommendation related to contraception and pregnancy testing in clinical trials" are mandatory. Highly effective birth control methods are required beginning at the screening visit and continuing until 6 months following last treatment with study drug. Negative serum pregnancy test for females of childbearing potential within 72hours of starting treatment. Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 6 months after final study drug administration. Two acceptable methods of birth control thus include Condom (barrier method of contraception) and one of the following is required ( established use of oral, or injected or implanted hormonal method of contraception by the female partner; placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; additional barrier method like occlusive cap with spermicidal foam/gel/film/cream/suppository in the female partner; tubal ligation in the female partner; vasectomy or other procedure resulting in infertility (eg., bilateral orchiectomy), for more than 6 months. Participant is willing and able to give informed consent for participation in the study. Exclusion Criteria: Patients who have completed chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) and hormonotherapy within 2 weeks, prior to treatment start. All acute toxic effects of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to a grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE). Participation in another clinical trial with any investigational agents within 30 days prior to study treatment start. History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-PSMAs or other agents used in the study. Medical or psychological conditions that would not allow the participant to understand, or sign the informed consent. 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.

Sites / Locations

  • UO Medicina Nucleare, IRCCS IRST
  • UO Medicina Nucleare, AUSL della Romagna

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

[177Lu]Lu-PSMA I&T

Arm Description

[177Lu]Lu-PSMA I&T, intravenous, dosage of 5.5 - 7.4 GBq every 8 weeks

Outcomes

Primary Outcome Measures

Acute toxicity rate
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)
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 Outcome Measures

progression-free survival (PFS)
PFS is defined as the time from the start treatment date to the date of first observation of documented disease progression (according to RECIST 1.1 or Prostate Cancer Clinical Trials Working Group (PCWG3) criteria for prostate cancer patients) or death due to any cause. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation.
overall survival (OS)
Overall survival is defined as the time from the therapy start to the date of death due to any cause or the date of last contact (censored observation) at the date of data cut-off.
late toxicity
The late toxicity is the toxicity that occurred after 30 days from the last treatment administration up to 6 months.
PET/CT response
PET/CT response is based on Standardized Uptake Value (SUV). PET/CT response will be evaluated with descriptive statistics.

Full Information

First Posted
March 24, 2023
Last Updated
May 10, 2023
Sponsor
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
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1. Study Identification

Unique Protocol Identification Number
NCT05867615
Brief Title
Radiometabolic Therapy With 177Lu PSMA in PSMA PET/CT Positive Advanced/Metastatic Tumours:
Acronym
LUBASKET
Official Title
Radiometabolic Therapy (RMT) With 177Lu PSMA in PSMA PET/CT Positive Advanced/Metastatic Tumours: a Basket Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 2023 (Anticipated)
Primary Completion Date
August 2026 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer
Keywords
basket study, PSMA PET/CT positive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
[177Lu]Lu-PSMA I&T
Arm Type
Experimental
Arm Description
[177Lu]Lu-PSMA I&T, intravenous, dosage of 5.5 - 7.4 GBq every 8 weeks
Intervention Type
Drug
Intervention Name(s)
[177Lu]Lu-PSMA I&T
Intervention Description
177Lu activity to be administered to single patient (range 5.5-7.4 GBq), every 8 weeks (±2 weeks) will be measured in a dose calibrator, properly calibrated for the radionuclide. The radiopharmaceutical will be slowly infused intravenously over 15-30' in a dedicated room using a dedicated pump system.
Primary Outcome Measure Information:
Title
Acute toxicity rate
Description
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.
Time Frame
40 months
Title
disease control rate (DCR)
Description
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
Time Frame
40 months
Secondary Outcome Measure Information:
Title
progression-free survival (PFS)
Description
PFS is defined as the time from the start treatment date to the date of first observation of documented disease progression (according to RECIST 1.1 or Prostate Cancer Clinical Trials Working Group (PCWG3) criteria for prostate cancer patients) or death due to any cause. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation.
Time Frame
68 months
Title
overall survival (OS)
Description
Overall survival is defined as the time from the therapy start to the date of death due to any cause or the date of last contact (censored observation) at the date of data cut-off.
Time Frame
68 months
Title
late toxicity
Description
The late toxicity is the toxicity that occurred after 30 days from the last treatment administration up to 6 months.
Time Frame
68 months
Title
PET/CT response
Description
PET/CT response is based on Standardized Uptake Value (SUV). PET/CT response will be evaluated with descriptive statistics.
Time Frame
68 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 reason or risk benefit balance, patients may be enrolled if CT or MRI strongly suggest oncological lesion confirming the Gallium-68 PET-CT PSMA positivity. Patients must have measurable disease; for patients with prostate cancer, also patients with only bone lesions can be enrolled. Relapse or progression of disease on CT scan and / or MRI; For patients with prostate cancer: documented radiological progression (in soft tissue and / or bone) and / or biochemical progression (sequence of Prostate-Specific Antigen (PSA) rising values from a minimal starting value ≥ 1 ng/ml) according to PCWG3. Patients with documented disease will be admitted to therapeutic phase only if the semi quantitative intensity of lesions uptake at the diagnostic PET/CT PSMA is higher than that of salivary glands or SUV has to be 1.5 times higher than the average total body No therapeutic alternatives Male or Female, aged>18 years Life expectancy of greater than 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status <2 Patients must have normal organ and marrow function If female of childbearing potential highly effective birth control methods, according to guideline "Recommendation related to contraception and pregnancy testing in clinical trials" are mandatory. Highly effective birth control methods are required beginning at the screening visit and continuing until 6 months following last treatment with study drug. Negative serum pregnancy test for females of childbearing potential within 72hours of starting treatment. Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 6 months after final study drug administration. Two acceptable methods of birth control thus include Condom (barrier method of contraception) and one of the following is required ( established use of oral, or injected or implanted hormonal method of contraception by the female partner; placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; additional barrier method like occlusive cap with spermicidal foam/gel/film/cream/suppository in the female partner; tubal ligation in the female partner; vasectomy or other procedure resulting in infertility (eg., bilateral orchiectomy), for more than 6 months. Participant is willing and able to give informed consent for participation in the study. Exclusion Criteria: Patients who have completed chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) and hormonotherapy within 2 weeks, prior to treatment start. All acute toxic effects of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to a grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE). Participation in another clinical trial with any investigational agents within 30 days prior to study treatment start. History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-PSMAs or other agents used in the study. Medical or psychological conditions that would not allow the participant to understand, or sign the informed consent. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Oriana Nanni
Phone
+390543739266
Email
oriana.nanni@irst.emr.it
First Name & Middle Initial & Last Name or Official Title & Degree
Bernadette Vertogen
Phone
+390544286058
Email
bernadette.vertogen@irst.emr.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maddalena Sansovini, MD
Organizational Affiliation
IRCCS IRST
Official's Role
Principal Investigator
Facility Information:
Facility Name
UO Medicina Nucleare, IRCCS IRST
City
Meldola
State/Province
Forlì
ZIP/Postal Code
47014
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maddalena Sansovini, MD
Phone
+390543739100
Email
maddalena.sansovini@irst.emr.it
First Name & Middle Initial & Last Name & Degree
Maddalena Sansovini, MD
Facility Name
UO Medicina Nucleare, AUSL della Romagna
City
Cesena
ZIP/Postal Code
47521
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Federica Matteucci, MD
Phone
+390543739332
Email
federica.matteucci@auslromagna.it
First Name & Middle Initial & Last Name & Degree
Federica Matteucci, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Radiometabolic Therapy With 177Lu PSMA in PSMA PET/CT Positive Advanced/Metastatic Tumours:

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