Efficacy of PErioperative PEmbrolizumab Treatment in Patients With Resectable Metastases From Kidney Cancer

NCT05578664 | Unknown Phase 2

• 1 other identifier: PE-PE
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II trial aiming at assessing the efficacy of pembrolizumab to delay tumor progression in patients with oligometastatic clear cell metastatic Renal Cell Carcinoma (mRCC). Eligible patients for this trial should have received previous surgery for primary tumor and have maximum of three metastases considered eligible for radical therapy (surgery or metastases directed radiotherapy). Eligible patients will be randomized 2:1 to receive:

• ARM A: pembrolizumab at flat dose of 400 mg every six weeks for a total of 9 cycles (one year of therapy) and metastasis directed treatment (surgery or RT) from day 21 of cycle 1 to day 42 of cycle 1; or
• ARM B: local therapy alone within 42 days.

Conditions

Oligometastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Relapsed Free Survival (RFS)

  The length of time from the randomization and the appearance of radiological progression of kidney cancer in patients who received pembrolizumab compared to those who did not

  24 months

Secondary Outcomes (4)

• Distant Relapsed Free Survival (Distant RFS)

  24 months

• Overall Survival (OS)

  24 months

• Safety Endpoint

  24 months

• Local Progression Disease (Local PD)

  24 months

Study Arms (2)

ARM A

EXPERIMENTAL

Pembrolizumab will be administered at flat dose of 400 mg IV every six weeks for a total of 9 cycles (one year of therapy) and metastasis directed treatment (surgery or RadioTherapy, RT) from day 21 of cycle 1 to day 42 of cycle 1.

Drug: Pembrolizumab injection plus metastasis directed treatment (surgery or RT); Other: Tumor resection or RT

ARM B

ACTIVE COMPARATOR

Local therapy alone (tumor resection or definitive RadioTherapy, RT) within 42 days from randomization.

Other: Tumor resection or RT

Interventions

Pembrolizumab injection plus metastasis directed treatment (surgery or RT) DRUG

Pembrolizumab 400 mg will be administered as a 30 minute IV infusion every 6 weeks for a total of 9 cycles (one year of therapy) and metastasis directed treatment (surgery or RT) from day 21 of cycle 1 to day 42 of cycle 1

ARM A

Tumor resection or RT OTHER

Tumor resection or RT will be applied within 42 days from randomization.

ARM A; ARM B

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of clear cell renal cell carcinoma will be enrolled in this study.
• Have undergone a partial nephrectomy or radical complete nephrectomy with negative surgical margins.
• Evidence of oligo-metastatic disease eligible for local treatment with radiotherapy or surgery, defined as:
• Appearance of new metastases within 5 years from previous eradication of primary tumors or previous metastasectomy.
• Presence of maximum 3 metastases in the same site or in different sites with the exception of bone metastases that cannot exceed the number of 2 if they are the sole disease site or one in case of multiple sites.
• Each metastasis should be less than 3 cm in the maximum diameter and less than 5 cm in the sum of the longest tumor diameters (this evaluation should apply also for lymph nodes).
• Has received no prior systemic therapy for Renal Cell Carcinoma (RCC).
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 7 days of before the start of study intervention.
• The participant (or legally acceptable representative) has provided documented informed consent/assent for the study.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a primary tumor or tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slide. Newly obtained biopsies are preferred to archived tissue.
• Female participants:
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 of the Study protocol OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatment(s)) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity after the last dose of study treatment.
• Adequate organ function defined as:

You may not qualify if:

• Has had major surgery, other than nephrectomy, within 4 weeks prior to randomization.
• Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has residual thrombus post nephrectomy in the vena renalis or vena cava.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization.
• Note: Participants must have recovered from all Adverse Events (AEs) due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, undergone CABG or PTCA, or cardiac arrhythmia.
• Note: Medically controlled arrhythmia stable on medication is permitted.
• Has moderate to severe hepatic impairment (Child-Pugh B or C).
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-muscle invasive bladder cancer, prostate cancer pT2 or less, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.

Sponsors & Collaborators

• Consorzio Oncotech: lead

Study Sites (1)

Fondazione Policlinico Universitario "A. Gemelli" IRCCS

Rome, RM, 00168, Italy

RECRUITING

MeSH Terms

Interventions

pembrolizumab; Surgical Procedures, Operative

Study Officials

• Roberto Iacovelli, MD, PhD

  Fondazione Policlinico Universitario "A. Gemelli" IRCCS - UOC Oncologia Medica, Rome

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roberto Iacovelli, MD, PhD

CONTACT

333 9516295; roberto.iacovelli@policlinicogemelli.it

PE-PE Study Team

CONTACT

pepe@oncotech.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are assigned to one of two groups (ARM A vs ARM B) in parallel for the duration of the study. Eligible patients will be randomized 2:1 to receive: * ARM A: pembrolizumab at flat dose of 400 mg every six weeks for a total of 9 cycles (one year of therapy) and metastasis directed treatment (surgery or RT) from day 21 of cycle 1 to day 42 of cycle 1; OR * ARM B: local therapy alone within 42 days.

Study Record Dates

• First Submitted: October 7, 2022
• First Posted: October 13, 2022
• Study Start: March 14, 2023
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2025
• Last Updated: August 30, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)