Retrospective Analysis of Patients With Metastatic Renal Cell Carcinoma Treated With CABOzantinib (CABOGEN)

Retrospective Analysis of Patients With Metastatic Renal Cell Carcinoma Treated With CABOzantinib: a GENomic Signature for Describing Long-lasting Response

CABOGEN is a Observational, retrospective, multicenter study that will enroll patients with metastatic clear cell renal carcinoma (mccRCC) treated with cabozantinib after one or more previous lines of treatment that included TKIs, immune checkpoint inhibitors or mTOR inhibitors.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Drug: Cabozantinib

Detailed Description

The aim of this study is to describe the genomic profiling of patients with metastatic renal cell carcinoma (mRCC) who are long-lasting responders to treatment with cabozantinib and patients who are not long-lasting responders to the cabozantinib treatment.

The study plan to enroll about 80 patients in 10 Italian centers:

Group A: 40 patients defined as long-lasting responders (PFS ≥ 9 months) Group B: 40 patients defined as primary refractories to cabozantinib (PFS ≤ 3 months)

Tissue samples from nephrectomy or from a metastatic site will be used to perform genomic profiling not older than 5 years.Tissue should be formalin-fixed, paraffin-embedded (FFPE).

Genomic profiling will be performed with a hybrid capture-based next-generation sequencing assay (FoundationONE). The sample will be assayed for all coding exons of 324 cancer-related genes plus select introns from 34 genes that are frequently rearranged in cancer. Sequencing will be performed to a mean exon coverage depth of >500X. The resulting sequences will be analyzed for all classes of genomic alteration, including short variant alterations, copy number alterations, and selected gene fusions or rearrangements.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Carmine Pinto, MD; Phone Number: +39 0522296614; Email: carmine.pinto@ausl.re.it

Study Locations

• Italy
  • Reggio Emilia, Italy, 42123
    • Recruiting
    • AUSL-IRCCS of Reggio Emilia
    • Contact: Carmine Pinto, MD; Phone Number: +39 0522296614; Email: carmine.pinto@ausl.re.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

patients with metastatic clear cell renal carcinoma (mRCC) who are long-lasting responders to treatment with cabozantinib and patients who are not long-lasting responders to the cabozantinib treatment. Cabozantinib treatment receive after one or more previuos therapy for mRCC

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Patients with histological diagnosis of predominantly clear cell carcinoma
• Availability of the tumor tissue from the primary tumor and/or a metastatic site for the genomic profiling analysis not older than 5 years.
• Evaluable disease according to RECIST criteria v 1.1
• Treatment with cabozantinib after one or more previous therapies for mRCC
• Patient progressed from the start to cabozantinib therapy within 3 months or after 9 months
• Any prognosis group according to the IMDC risk score
• Signed informed consent must be obtained for living patients. Patients who died and patient untraceable will be analyzed based on the Authorization no. 9/2016 of the Italian Data Protector Supervisor.

Exclusion Criteria:

• Non-availability of tumor tissue from the primary tumor or a metastatic site for biomarker analysis
• Patient progressed between 3 and 9 months from the beginning of treatment with cabozantinib.
• Non-availability of clinical information useful to evaluate the IMDC risk group at baseline.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A: long-lasting responders; Patient long-lasting responders (PFS ≥9 months) to cabozantinib	Drug: Cabozantinib; Patients must have been treated with cabozantinib after one or more previous therapies for mRCC, as per clinical practise.
Group B: primary refractories; Patient progressed from the start to cabozantinib therapy within 3 months	Drug: Cabozantinib; Patients must have been treated with cabozantinib after one or more previous therapies for mRCC, as per clinical practise.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genomic profiling	to describe genomic profiling of patients with mRCC who are long-lasting responders (PFS ≥9 months) to cabozantinib and describe genomic profiling of patients with rapid disease progression following cabozntinib therapy (PFS≤ 3 months)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	to describe OS based according to detected genomic profiling	12 months
Overall response rate (ORR)	to describe ORR according to the detected genomic profiling	12 months
Duration of response (DOR)	to describe duration of response (DOR) according to the detected genomic profilingto describe the genomic profiling according to treatment line (second, third or subsequent) to describe anamnestic characteristics (weight, ECOG PS, sites of metastasis, response to previous treatment lines)	12 months

Collaborators and Investigators

• Sponsor: Gruppo Oncologico Italiano di Ricerca Clinica
• Collaborators: Ipsen; Yghea
• Investigators: Principal Investigator: Carmine Pinto, MD, AUSL/IRCCS of Reggio Emilia; Study Chair: Cristina Masini, MD, AUSL/IRCCS of Reggio Emilia; Study Chair: Stefania Di Girolamo, MD, AUSL/IRCCS of Reggio Emilia

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: August 8, 2024
• First Submitted That Met QC Criteria: August 8, 2024
• First Posted (Actual): August 12, 2024

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Metastatic Renal Cell Carcinoma; Genomic signature; long lasting response; cabozantinib treatment
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: GOIRC-08-2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No