Nivolumab in mRCC Patients: Treg Function, T-cell Access and NK Interactions to Predict and Improve Efficacy

NCT03891485 | Completed FDA Drug

• 1 other identifier: 21/16 oss
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The project aims to identify Nivolumab predictive biomarkers in metastatic renal cancer patients through functional evaluation of peripheral Tregs and NKs. Moreover the efficacy of new CXCR4 antagonists (PCT/IB2011/000120/ EP2528936B1/ US2013/0079292A1) will be ex vivo evaluated in modulating Tregs and NKs function

Conditions

RCC; Metastatic Renal Cell Carcinoma

Keywords

Nivolumab; CXCR4 antagonist; mRCC; Tregs-NKs

Outcome Measures

Primary Outcomes (2)

• Tregs function on peripheral blood/neoplastic tissue from mRCC patients undergoing nivolumab treatment.

  Treg function will be mesured as % inhibition of T-effector proliferation (Tregs/T-effector 1:1 ratio). %T-effector proliferation in the presence of patients derived Tregs (Tregs/T-effector 1:1). Ex vivo effect of CXCR4 antagonists ( PCT/IB2011/000120; EP 2 528 936 B1/US2013/0079292A1) and other Tregs targets antagonists (ICOS, CD39/CD73) or agonists (TLR7L) will be assessed to identify novel anti-PD1 resistance mechanisms.

  Evolution between inclusion up to 24 months

• NK function/cytotoxicity on peripheral blood/neoplastic tissue from mRCC patients undergoing nivolumab treatment

  NK cytotoxicity will be measured as % NK cell degranulation (CD107a assay), intracellular staining Grz A and GrzB and intracellular cytokines, GM-CSF, IFNγ, IL-10, TNF. Ex vivo effect of CXCR4 antagonists will be evaluated on NK cytotoxicity.

  Evolution between inclusion and up to 24 months

Secondary Outcomes (1)

• Exploration of the biological rationale for coupling CXCR4 antagonist with anti-PD-1 in in vivo models of RCC (mice models)

  36 months

Interventions

Immunological and tumour characterization BIOLOGICAL

FFPE, blood samples (liquid biopsy, heparin and EDTA blood) performed in patients presenting a renal metastatic cancer receiving treatment as standard practice according to physician's choice (2nd or 3rd line of treatment with nivolumab, or other second line according to physician's choice)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Men and women with histological confirmation of advanced/metastatic RCC

You may qualify if:

• Age ≥ 18 years-old.
• Histology proven locally advanced (unresectable) or metastatic clear cell renal cell carcinoma (mccRCC).
• Starting 2nd or 3rd line of treatment with nivolumab, everolimus or axitinib
• Signed informed consent.

You may not qualify if:

• Psychological, familial, sociological, geographical conditions that would limit compliance with study protocol requirements.
• Pregnant or breastfeeding woman

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

IRCCS Istituto Nazionale Tumori di Napoli

Naples, 80131, Italy

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Archival FFPE specimen. Blood samples performed during standard visits and not requiring additional blood tests: * Heparin blood * EDTA blood

MeSH Terms

Conditions

Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2019
• First Posted: March 27, 2019
• Study Start: December 1, 2016
• Primary Completion: September 1, 2022
• Study Completion: August 30, 2023
• Last Updated: March 11, 2025

Record last verified: 2023-03

Locations

IT (1)