Primary Metastatic Renal Cell Carcinoma Treated With Immunecheckpoint Inhibitors and Cytoreductive Nephrectomy (PrimerX)

A Prospective Study of Primary Metastatic Renal Cell Carcinoma Treated With Immunecheckpoint Inhibitors and Cytoreductive Nephrectomy vs Primary Tumour in Place

The benefit of deferred Cytoreductive Nephrectomy (CN) has to be re-assessed in the context of IO +IO and IO + TKI systemic treatment. Given the benefit of CN in the setting of first generation immunotherapy, it is conceivable that both trials underestimated the benefit of CN, in absence of immunotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Procedure: Cytoreductive Nephrectomy

Detailed Description

In past years, much research has been done into the beneficial effects of cytoreductive nephrectomy in patients with metastatic renal cancer receiving systemic therapy with positive results. In the meantime systhemic therapy, and in particular immunotherapy, have changed. Patients with metastatic renal cancer are increasingly treated with immunocheckpoint inhibitors, but the effect of adding cytoreductive nephrectomy in this group of patients has not yet been investigated. The aim of this study is to investigate whether performing a cytoreductive nephrectomy has a beneficial effect on overall survival in patients with metastatic renal cancer receiving systemic therapy using immunocheckpoint inhibitors.

A randomized controlled trial. All eligible patients have already been enrolled in the PRO-RCC registry, a registry that collects prospective observational data, and have also given consent to be included in other studies as a control cohort. This design is called a TWiC (trial within cohort). After randomization, patients who are randomized into the therapy arm will receive a patient information via their treating physician. Upon participation, an informed consent will be signed and the patient will be scheduled for surgery.

• Study Type: Interventional
• Enrollment (Estimated): 750
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Adriaan Bins, MD PhD; Phone Number: 020 5665955; Email: a.d.bins@amsterdamumc.nl
• Study Contact Backup: Name: Axel Bex, MD PhD; Phone Number: 020 512 9111; Email: a.bex@nki.nl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female patients age ≥ 18 years
2. Signed and written informed consent Note: Written and signed informed consent will be obtained before any study procedures, including study-specific-screening procedures, has been performed.
3. Informed consent obtained for being offered future experimental interventions within the PRO-RCC project.
4. Histologically confirmed diagnosis of metastatic clear cell, papillary or chromophobe renal cell carcinoma of intermediate to poor risk, including sarcomatoid features, with
5. World Health Organization (WHO) performance status of 0-1.
6. Surgical candidates based on surgeon and anesthetist assessment
7. Treatment with an IO combination (IO+IO or IO+TKI) as standard of care for metastatic RCC
8. Absence of progression at metastatic sites at time of identification (6month after start of systemic first line treatment). 9) Primary tumor in situ 10) Participation in the PRO-RCC prospective cohort.

Exclusion Criteria:

NA

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cytoreductive Nephrectomy; Cytoreductive Nephrectomy within 6 months to 1 year after start systemic therapy for metastatic Renal Cell Carcinoma	Procedure: Cytoreductive Nephrectomy; The experimental intervention consists of cytoreductive nephrectomy (CN) or any ablative local therapy within 6 months and 1 year after start of systemic treatment. All types of ablative local therapy are allowed as a substitute for CN
No Intervention: Standard of Care; Standard of Care for metastatic Renal Cell Carcinoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall Survival Using Kaplan Meier Survival analysis	defined as time from randomization to death of any cause during 5 years of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long term Quality of Life outcomes using validated EORTC Quality of Life Questionnaire (QLQ-C30)	using the Dutch validated EORTC Quality of Life Questionnaire (QLQ-C30)	Post operative follow-up period during 5 years
Surgical morbidity outcomes using Clavien Dindo classification of surgical morbidity	Clavien Dindo classification of surgical morbidity is used to classify morbidity outcomes	Post operative follow-up period during 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical data and annotated tissue for translational research into mechanisms of treatment response and resistance.	In detail, we will examine the intratumor alteration of tumor infiltrating CD8, CD4, NK(T) cells (CD56+,CD3+-), and the distribution of these NK cells in the tumor, as these cells have been shown to be involved in anti-tumor responses in RCC.	post-operative follow-up period during 5 years

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Comprehensive Cancer Centre The Netherlands
• Investigators: Principal Investigator: Adriaan Bins, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; Tyrosine Kinase Inhibitor; Cytoreductive Nephrectomy
• 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: 83948

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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