Phase I/II Study Evaluating PSMA Targeted Radionuclide Therapy in Adult Patients With Metastatic Clear Cell Renal Cancer

NCT06059014 | Completed Phase 1 DMC

• 1 other identifier: ET22-313
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open label Phase I/II study conducted according to a Fleming design, investigating the safety and the efficacy of 4 IV injections of 177Lu-PSMA-1 in patients with metastatic clear cell renal cancer. This trial is divided in 2 parts:

• A safety run-in part aiming to assess the safety of 177Lu-PSMA-1 (with 6 patients treated at the starting activity = 7.4 GBq of 177Lu-PSMA-1, every 6 weeks (Q6W) for 4 administrations). If more than one patient experiences a ST during the first cycle of therapy (6 weeks), then a lower activity of 177Lu-PSMA-1 will be evaluated in an additional cohort of 6 patients (5.9 GBq). The 6 patients from this safety run-in step, treated at the activity selected for phase II, will be included in the evaluation of Phase II part.
• A Phase II part aiming to assess the clinical activity of 177Lu-PSMA-1

Conditions

Metastatic Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of Severe Toxicities (ST) (for Phase1 part)

  Incidence of Severe Toxicities (ST) defined as specific adverse events (AEs) graded using NCI-CTCAE V5.0 occurring during the ST period (i.e. the 6 first weeks) and assessed as related to study drug and considered clinically significant. The sepcific adverse events are defined in the protocol.

  during the first 6 weeks of treatment

• Disease Control Rate after 24 weeks of treatment (DCR24w) (for Phase II part)

  Disease Control Rate after 24 weeks of treatment (DCR24w) is defined as the rate of patients with a stable disease, a complete or partial response according to RECIST v1.1.after 24 weeks of treatment.

  at 24 weeks of treatment

Study Arms (1)

177Lu-PSMA-1

EXPERIMENTAL

Radiopharmaceutical - injectable solution

Drug: 177Lu-PSMA-1 (radiopharmaceutical)

Interventions

177Lu-PSMA-1 (radiopharmaceutical) DRUG

7.4 GBq (or 5.9 GBq in case of lower actvity) of 177Lu-PSMA-1, every 6 weeks for 4 administirations

177Lu-PSMA-1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I1. Male or female patients aged ≥ 18 years at time of informed consent signature.
• I2. Patient with histologically confirmed diagnosis of metastatic clear cell renal cell carcinoma (mccRCC) previously treated by at least 2 lines of therapy in the advanced/metastatic setting including at least 1 line of anti-VEGFR and 1 line of immunotherapy.
• I4. Patient with PSMA-PET positive lesions (68Ga-PSMA-PET):
• For patient with only extrahepatic disease: ≥ 50% of positive extrahepatic metastatic lesions
• For patient with both extra-hepatic and liver metastasis: ≥ 50% of positive extrahepatic metastatic lesions and ≥ 80 % of positive supracentimetric liver metastatic lesions.
• For patient with only liver metastatic lesions: ≥ 80 % of positive supracentimetric lesions.
• I5. Life expectancy ≥ 3 months.
• I6. Eastern Cooperative Oncology Group performance status 0, 1 or 2.
• I7. Demonstrate adequate organ function as defined in the protocol.
• I8. Women of child-bearing potential must have a negative urine pregnancy test at screening (within 72 hours prior C1D1) and must agree to use 1 effective form of contraception from the time of the treatment period and of the negative pregnancy test up to 6 months after the last administration of study drug. Effective forms of contraception are listed in the protocol.
• I9. Fertile males must use highly effective contraception during the dosing period and through 6 months after final administration of study drug.
• I10. Patient should be able and willing to comply with study visits and procedures as per protocol.
• I11. Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.
• I12. Patients must be covered by medical insurance.

You may not qualify if:

• E1. Patients with known active central nervous system (CNS) metastases and/or epidural metastases. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to C1D1 and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids (at doses higher than 10 mg/d of methylprednisolone or equivalent) for at least 4 weeks prior to C1D1.
• E2. Patients previously treated with any radiopharmaceutical, excluding 68Ga-PSMA required during screening for this protocol.
• E3. Persisting toxicities related to previous anti-cancer therapy which were not resolved to grade ≤1 (except: anaemia provided that criterion I7 is met) and /or any persistent irAE of any grade (except adequately controlled irAE (e.g: with replacement therapy for endocrine irAE)).
• E4. History, within 2 years, of cancer other than renal cancer, except for basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, localized prostate cancer.
• E5. History of idiopathic pulmonary fibrosis, non-infectious pneumonitis, interstitial lung disease that required steroids or has current pneumonitis, interstitial lung disease, drug-induced pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• E6. Prior therapy or a need to be treated with a forbidden concomitant/concurrent therapies/procedure as defined per protocol.
• E7. Patients with clinically significant hematuria, hematemesis, or hemoptysis exceeding 0.5 teaspoon (2.5 mL) of red blood, as well as those with a history of coagulopathy or other significant bleeding (e.g., pulmonary hemorrhage) within the 3 months prior to the initiation of the study treatment. Patients receiving anticoagulation medication will be eligible only if the dosage and route of administration have remained stable since at least 2 weeks prior to C1D1.
• E8. Patients with an active uncontrolled infection. E9. Women pregnant or breastfeeding. E10. Patients placed under a legal protection regimen such as: Judicial Safeguards, curatorship or guardianship

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (1)

Centre Leon Berard

Lyon, 69008, France

Location

Related Publications (1)

• Kryza D, Vinceneux A, Bidaux AS, Garin G, Tatu D, Cropet C, Badel JN, Perol D, Giraudet AL. A multicentric, single arm, open-label, phase I/II study evaluating PSMA targeted radionuclide therapy in adult patients with metastatic clear cell renal cancer (PRadR). BMC Cancer. 2024 Feb 1;24(1):163. doi: 10.1186/s12885-023-11702-8.

  PMID: 38302933 DERIVED

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma

Interventions

Radiopharmaceuticals

Intervention Hierarchy (Ancestors)

Diagnostic Uses of Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Molecular Mechanisms of Pharmacological Action; Indicators and Reagents; Laboratory Chemicals; Specialty Uses of Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: September 28, 2023
• Study Start: November 9, 2023
• Primary Completion: July 16, 2025
• Study Completion: July 16, 2025
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)