Radiometabolic Therapy (RMT) with 177Lu PSMA in PSMA PET/CT positive advanced/metastatic tumours: a basket trial (LUBASKET)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 May 2023 → ongoing

Decision date (initial)

2025-01-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519346-75-00

EudraCT number

2022-003162-20

ClinicalTrials.gov

NCT05867615

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The main objective of this phase II study is to evaluate the disease control rate (DCR) and safety as co-primary objective in different histologies.

Secondary objectives 4

1. Progression-free survival (PFS)
2. Overall survival (OS)
3. Late toxicity
4. PET/CT response and dosimetry

Conditions and MedDRA coding

PSMA PET/CT positive advanced/metastatic tumours

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 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;
2. patients must have measurable disease; patients with prostate cancer who have only bone lesions can be enrolled;
3. relapse or progression of disease on CT/MRI scan and/or WBD-MRI;
4. 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 g >=1 ng/ml) according to PCWG3;
5. patients will be admitted to therapeutic phase only if the diagnostic PET/CT PSMA SUV max is >= g 3;
6. no therapeutic alternatives
7. male or Female, aged >= 18 years
8. life expectancy of greater than 12 weeks
9. ECOG performance status <= 2
10. patients must have normal organ and marrow function as defined below: leukocytes >= 3,000/µL; absolute neutrophil count >= 1,500/µL; hemoglobin >= 9 g/dL; platelets >= 100,000/µL; total bilirubin <= 1.5 X institutional upper normal limit (this will not apply to patients with confirmed Gilbert’s syndrome); AST(SGOT)/ALT(SGPT) <= 2.5 X institutional upper normal limit (< 5 X UNL in presence of liver metastases); creatinine <= 2 mg/dL
11. A female participant is eligible to participate if she is not pregnant and not breastfeeding;
12. Participant is willing and able to give informed consent for participation in the study.

Exclusion criteria 6

1. patients who have completed chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) and hormonotherapy within 2 weeks (excluding mCRPC patients), prior to treatment start. A window of 3 days is permitted;
2. all acute toxic effects of any prior therapy (including surgery, radiation therapy, and chemotherapy) must have resolved to a grade f 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE);
3. participation in another clinical trial with any investigational agents within 30 days prior to study treatment start. A window of 3 days is permitted;
4. history of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-PSMAs or other agents used in the study
5. medical or psychological conditions that would not allow the participant to understand, or sign the informed consent;
6. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 patients with prostate cancer (according to PCWG3 criteria), at the 1st planned evaluation. Safety, evaluated according to version 5.0 CTC-AE. Safety is defined as the percentage of patients who experience acute toxicity from the 1st treatment until 30 days after the last treatment cycle.

Secondary endpoints 4

1. 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 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.
2. 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.
3. The late toxicity is the toxicity that occurred after 30 days from the last treatment administration up to 6 months.
4. PET/CT response is based on SUV. The dosimetry objective is evaluated through pharmacokinetic measures, biodistribution activity and absorbed dose to salivary gland (critical organ), kidneys, bone marrow and tumour.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Sponsor organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Address

Via Piero Maroncelli 40

City

Meldola

Postcode

47014

Country

Italy

Scientific contact point

Organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Contact name

Maddalena Sansovini

Public contact point

Organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Contact name

Oriana Nanni

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications