AzTrials
AzTrials

Oligometastatic Renal Cell CarcinomaPhase 2PE-PENCT05578664

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

A Phase 2 study testing Pembrolizumab injection plus metastasis directed treatment (surgery or RT) and Tumor resection or RT in people with Oligometastatic Renal Cell Carcinoma, run by Consorzio Oncotech at 33 sites in Italy.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Oligometastatic Renal Cell Carcinoma
What is being tested?
Pembrolizumab injection plus metastasis directed treatment (surgery or RT) and Tumor resection or RT
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
85 participants
Where
33 sitesItaly
Study dates
14 Mar 2023to Feb 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 29Show fewer
  • 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:
  • System - Laboratory Value
  • Hematological
  • Absolute neutrophil count (ANC): ≥ 1500/μl
  • Platelets: ≥ 100 000/μl
  • Hemoglobin: ≥ 9.0 g/dL or ≥ 5.6 mmol/L
  • Renal
  • Creatinine: ≤1.5 x Upper Limit of Normal (ULN) OR
  • Measured or calculated creatinine clearance: ≥ 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (GFR can also be used in place of creatinine or CrCl)
  • Hepatic
  • Total bilirubin: ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 x ULN
  • Aspartate transaminase (AST or SGOT) and alanine transaminase (ALT or SGPT): ≤ 2.5 x ULN (≤ 5 ULN for participants with liver metastases)
  • Coagulation
  • International normalized ratio (INR) OR prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT): ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

Who cannot join

  • 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
Show all 28Show fewer
  • 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.
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously surgically treated brain metastases may participate provided they are not radiological evidence of disease at the time of screening and without evidence of progression for at least 12 months by repeat imaging (note that the repeat imaging should be performed during study screening).
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has a known history of Human Immunodeficiency Virus (HIV) infection.
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (HCV, defined as HCV RNA is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
  • Has had an allogenic tissue/solid organ transplant.
  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

Italy33 sites

  • A.O.U. Consorziale Policlinico di Bari

    Bari, BA, 70124

  • ASST Papa Giovanni XXIII

    Bergamo, BG, 24127

  • IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi

    Bologna, BO, 40138

  • ASST Spedali Civili di Brescia

    Brescia, BS, 25123

  • AOU Cagliari

    Cagliari, California, 09042

  • Fondazione del Piemonte per l'Oncologia - IRCCS

    Candiolo, TO, 10060

  • AOE Cannizzaro

    Catania, CT, 95126

  • ASST Cremona

    Cremona, CR, 26100

  • AUO Careggi

    Florence, FI, 50134

  • IRCCS Policlinico San Martino

    Genova, GE, 16132

  • P.O. Vito Fazzi

    Lecce, LE, 73100

  • Azienda Usl Toscana Nord Ovest

    Livorno, LI, 57124

  • Istituto Europeo di Oncologia

    Milan, Michigan, 20141

  • Fondazione IRCCS INT Milano

    Milan, MI, 20133

  • AOU Policlinico di Modena

    Modena, MO, 41124

  • AORN Antonio Cardarelli

    Naples, 80131

  • AOU Maggiore della Carità

    Novara, 28100

  • AOU S. Luigi Gonzaga

    Orbassano, TO, 10043

  • Istituto Oncologico Veneto - IRCCS

    Padova, PD, 35128

  • Ospedale A. Tortora

    Pagani, SA, 84016

  • Casa di Cura La Maddalena s.p.a.

    Palermo, Pennsylvania, 90146

  • Azienda Ospedaliero-Universitaria di Parma

    Parma, PR, 43126

  • Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia

    Perugia, PG, 06132

  • Azienda Ospedaliero-Universitaria Pisana

    Pisa, PI, 56126

  • P.O. "S. Maria delle Grazie"

    Pozzuoli, 80078

  • Azienda Sanitaria Territoriale di Macerata

    Province of Macerata, MC, 62100

  • AUSL/IRCCS di Reggio Emilia

    Reggio Emilia, RE, 42123

  • Istituti Fisioterapici Ospitalieri

    Roma, RM, 00144

  • Fondazione Policlinico Universitario "A. Gemelli" IRCCS

    Rome, RM, 00168

  • IRCCS Istituto Clinico Humanitas

    Rozzano, MI, 20089

  • Azienda Ospedaliera S. Maria

    Terni, TR, 05100

  • AOUI Verona - Borgo Roma

    Verona, VR, 37134

  • Presidio Ospedaliero di Belcolle

    Viterbo, Vermont, 01100

Other trials in Italy

About this study

Official title: Efficacy of PErioperative PEmbrolizumab Treatment in Patients With Resectable Metastases From Kidney Cancer. (The PE-PE Study).

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.
Read the detailed description

In this study, approximately 81 participants with ccRCC will be enrolled. The RESORT and E2810 clinical trials reported a rate of patients free of relapse of about 50% at 24 months. This study aims to improve this rate from 50% to 70% corresponding to an Hard Ratio of 0.51. Therefore, the sample size required for demonstrating this relapse-free survival (RFS) advantage includes a total of 74 patients that will be randomized 2:1 in the arm A or B respectively. The study will detect a treatment difference with the 80% probability at a one-sided p and 10.0% significance level, if the true hazard ratio is 0.51. This is based on the assumption that the accrual period will be 30 months, the follow up period will be 24 months, and the median RFS is 24 months.

Because 10% of dropout has been estimated, the final number of patients is 81.

Being tested
Pembrolizumab injection plus metastasis directed treatment (surgery or RT), Tumor resection or RT

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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

  • Tumor resection or RTOther

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

Study groups in NCT05578664
Study groupRoleWhat they receive
ARM AExperimentalPembrolizumab 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.
Receives: Drug: Pembrolizumab injection plus metastasis directed treatment (surgery or RT); Other: Tumor resection or RT
ARM BActive comparatorLocal therapy alone (tumor resection or definitive RadioTherapy, RT) within 42 days from randomization.
Receives: Other: Tumor resection or RT

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 24 months

Secondary outcomes (4)

  1. Distant Relapsed Free Survival (Distant RFS)

    The length of time from the randomization to the appearance of distant metastases outside those treated with surgery or radiotherapy.

    Measured: 24 months

  2. Overall Survival (OS)

    The time from the randomization to the patient's death or last contact in patients who received pembrolizumab compared to those who did not.

    Measured: 24 months

  3. Safety Endpoint

    The overall incidence of adverse events in patients who received pembrolizumab compared to those who did not.

    Measured: 24 months

  4. Local Progression Disease (Local PD)

    The overall incidence local progression in patients who received pembrolizumab plus RT compared to those who received RT alone

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2022
  2. Study start14 Mar 2023
  3. Primary completionMar 2028 (estimated)
  4. Study completionFeb 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05578664
Sponsor's protocol ID
PE-PE
Acronym
PE-PE
Status last verified
Oct 2026
First submitted
7 Oct 2022
Last updated
21 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab injection plus metastasis directed treatment (surgery or RT) and Tumor resection or RT in people with Oligometastatic Renal Cell Carcinoma, run by Consorzio Oncotech at 33 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relapsed Free Survival (RFS) (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05578664.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in