Renal Cell Carcinoma, Clear Cell, SomaticPhase 2NAPSTERNCT05024318
NeoAdjuvant Pembrolizumab and STEreotactic Radiotherapy Prior to Nephrectomy for Renal Cell Carcinoma
A Phase 2 study testing Pembrolizumab, Stereotactic Ablative Radiotherapy and Nephrectomy in people with Renal Cell Carcinoma, Clear Cell, Somatic, run by Peter MacCallum Cancer Centre, Australia at 2 sites in Australia.
Trial summary
This is a prospective, open label, phase II, randomised, non-comparative clinical trial, evaluating changes in tumour-responsive T-cells following neoadjuvant stereotactic ablative body radiotherapy (SABR) with or without pembrolizumab, prior to nephrectomy, in patients with localised primary clear cell renal cell… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma, Clear Cell, Somatic
- What is being tested?
- Pembrolizumab, Stereotactic Ablative Radiotherapy and Nephrectomy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesAustralia
- Study dates
- 8 Feb 2022to Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Patient has provided written informed consent
- Male or female aged 18 years or older at written informed consent
- Histologically or cytologically confirmed diagnosis of RCC with clear cell, rhabdoid or sarcomatoid components
- Tumour stage T1B-T3, N0 or N1, M0 or low volume M1 planned for nephrectomy
- Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to randomisation:
- White Blood Cell (WBC) ≥ 3 X 10^9/L
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- Absolute neutrophil count (ANC) ≥1.5 X 10^9/L
- Platelets ≥ 100 X 10^9/L
- Haemoglobin ≥ 100 g/L independent of transfusion
- Serum Creatinine ≤1.5 X Upper Limit of Normal (ULN) or measured or calculated CrCl calculated as per institutional standard ≥ 30 ml/min. GFR can also be used in place of serum creatinine or CrCl.
- Total bilirubin ≤1.5 X ULN except for patients with known Gilbert's Syndrome
- Albumin > 30 g/L
- AST and ALT ≤1.5 X ULN
- INR or PT ≤1.5 X ULN unless patient is receiving anticoagulant therapy
- ECOG performance status of 0 or 1
- Women of child birth potential (WOCBP) must have a negative urine or serum pregnancy test within 72 hours prior to randomisation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- WOCBP should be willing to use two methods of birth control, or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilised or have not been free from menses for more than 1 year
- Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
- Patient agrees to the collection and use of their fresh tumour samples and peripheral blood for translational research
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing biopsies, treatment, and scheduled visits and examination
Who cannot join
- Had prior treatment with any anti-PD-1, or anti-PD-L1, or PD-L2 agent or with an antibody targeting any other immune-regulatory receptors or mechanisms. Examples of such antibodies include antibodies against IDO, PD-L1, IL-2R, and GITR
- Known or active inflammatory bowel disease involving colon and small bowels
- Previous radiotherapy to the upper abdomen with radiation dose overlap to the involved kidney
- 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 randomisation
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy exceeding 10 mg daily dose of prednisone or equivalent or any other form of immunosuppressive therapy within 7 days prior to randomisation
- Has an active autoimmune disease that has required systemic treatment in the last 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
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- Has a known additional malignancy that is progressing or has required active treatment in the last 2 years Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ, such as breast cancer in situ, that has undergone potentially curative therapy are not excluded
- Has known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to randomisation
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has an active infection requiring systemic therapy
- Has a known history of HIV infection
- Has known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive)or known active Hepatitis C (defined as HCV RNA [qualitative] is detected) infection
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
- Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Has received a live virus vaccine within 30 days prior to randomisation. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed
- Has had a prior solid organ transplant
- 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 study drug.
- Any contraindications for surgery
Trial locations and contacts
2 sites in 1 country.
Australia2 sites, 2 recruiting
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Shankar Siva, A/Prof, +61 3 8559 7988, Shankar.Siva@petermac.org
Arun Azad, A/Prof, +61 3 8559 7165, Arun.Azad@petermac.org
- Recruiting
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
David Pryor
About this study
Official title: NeoAdjuvant Pembrolizumab and STEreotactic Radiotherapy Prior to Nephrectomy for Renal Cell Carcinoma: Investigating Induced Immune Context Changes
This is a prospective, open label, phase II, randomised, non-comparative clinical trial, evaluating changes in tumour-responsive T-cells following neoadjuvant stereotactic ablative body radiotherapy (SABR) with or without pembrolizumab, prior to nephrectomy, in patients with localised primary clear cell renal cell carcinoma (ccRCC).
- Being tested
- Pembrolizumab, Stereotactic Ablative Radiotherapy, Nephrectomy
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called MK-3475
Pembrolizumab 200 mg tobe administered as a 30 minute IV infusion every 21 days for 3 cycles
Stereotactic Ablative RadiotherapyRadiation
Also called SABR
42Gy delivered in 3 fractions
NephrectomyProcedure or surgery
Also called Surgical removal of a kidney
Partial or total nephrectomy performed 9-12 weeks after first dose of Pembrolizumab
| Study group | Role | What they receive |
|---|---|---|
| SABR plus nephrectomy | Active comparator | Stereotactic Ablative Radiotherapy (SABR) will be prescribed to a dose of 42Gy in 3 fractions. All radiotherapy treatment be completed within 3 weeks.Patients will undergo nephrectomy within 9-12 weeks after the first dose of treatment. Receives: Radiation: Stereotactic Ablative Radiotherapy; Procedure: Nephrectomy |
| Pembrolizumab followed by SABR after cycle 1 plus nephrectomy | Experimental | Pembrolizumab 200 mg (flat dose) will be administered as a 30 minute IV infusion every 21 days for 3 cycles. Patients will receive 1 cycle of pembolizumab prior to SABR followed by an additional 2 cycles of pembrolizumab (1 cycle is 21 days). Patients will undergo nephrectomy 9-12 weeks after commencement of treatment. Receives: Drug: Pembrolizumab; Radiation: Stereotactic Ablative Radiotherapy; Procedure: Nephrectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
mPR post-SABR with or without pembrolizumab
The mPR rate is defined as <10% residual tumour at post-nephrectomy specimens
Measured: At nephrectomy performed 9-12 weeks after first dose of pembrolizumab
CD8+ TRM in baseline biopsy and post-nephrectomy specimen, all measured as a continuous variable.
To describe changes in tumour-responsive T-cells, TRM CD8+ T-cells from baseline to post-nephrectomy in patients treated with SABR with or without pembrolizumab treatment followed by nephrectomy
Measured: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
TCF-1 + tumour infiltrating lymphocytes (TILs) in baseline biopsy and post-nephrectomy specimen, measured as a continuous variable
To describe changes in TCF-1+ T-cells from baseline to post-nephrectomy in patients treated with SABR with or without pembrolizumab treatment followed by nephrectomy
Measured: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Secondary outcomes (5)
Immune response cells in baseline biopsy and post-nephrectomy specimen
Change in immune response from baseline to post-nephrectomy
Measured: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
The tumour-responsive TRM cells inclusive of CD4+ and CD8+ compartments
Percentage of tumour responsive T-cells (inclusive CD4/CD8) after neo-adjuvant treatment
Measured: 2 weeks prior to nephrectomy
Safety of SABR with or without pembrolizumab in the neo-adjuvant setting
Adverse events, as measured by CTCAE v5.0
Measured: 60 days post nephrectomy
Change in immune response associated with mPR
Immune response cells in baseline biopsy and post-nephrectomy specimens
Measured: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Change in PD-L1 and PD-L2 expression in tumour
PD-L1 and PD-L2 expression in baseline biopsy and post-nephrectomy specimens
Measured: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2021
- Study start8 Feb 2022
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell Carcinoma, Clear Cell, SomaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peter MacCallum Cancer Centre, Australia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shankar Siva, A/Prof, Study chair, Peter MacCallum Cancer Centre, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05024318
- Sponsor's protocol ID
- 19/007
- Acronym
- NAPSTER
- Status last verified
- May 2024
- First submitted
- 29 Mar 2021
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NeoAdjuvant Pembrolizumab and STEreotactic Radiotherapy Prior to Nephrectomy for Renal Cell Carcinoma: Investigating Induced Immune Context Changes
- ClinicalTrials.gov ID
- NCT05024318
- Acronym / sponsor ID
- NAPSTER / 19/007
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Peter MacCallum Cancer Centre, AustraliaUniversity, hospital or other
- Study start
- 8 Feb 2022 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 27 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, open label, phase II, randomised, non-comparative clinical trial, evaluating changes in tumour-responsive T-cells following neoadjuvant stereotactic ablative body radiotherapy (SABR) with or without pembrolizumab, prior to nephrectomy, in patients with localised primary clear cell renal cell carcinoma (ccRCC).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SABR plus nephrectomy | Active comparator | Radiation: Stereotactic Ablative Radiotherapy, Procedure: NephrectomyStereotactic Ablative Radiotherapy (SABR) will be prescribed to a dose of 42Gy in 3 fractions. All radiotherapy treatment be completed within 3 weeks.Patients will undergo nephrectomy within 9-12 weeks after the first dose of treatment. |
| Pembrolizumab followed by SABR after cycle 1 plus nephrectomy | Experimental | Drug: Pembrolizumab, Radiation: Stereotactic Ablative Radiotherapy, Procedure: NephrectomyPembrolizumab 200 mg (flat dose) will be administered as a 30 minute IV infusion every 21 days for 3 cycles. Patients will receive 1 cycle of pembolizumab prior to SABR followed by an additional 2 cycles of pembrolizumab (1 cycle is 21 days). Patients will undergo nephrectomy 9-12 weeks after commencement of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patient has provided written informed consent
- Male or female aged 18 years or older at written informed consent
- Histologically or cytologically confirmed diagnosis of RCC with clear cell, rhabdoid or sarcomatoid components
- Tumour stage T1B-T3, N0 or N1, M0 or low volume M1 planned for nephrectomy
- Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to randomisation:
Key exclusion criteria (19 listed)
- Had prior treatment with any anti-PD-1, or anti-PD-L1, or PD-L2 agent or with an antibody targeting any other immune-regulatory receptors or mechanisms. Examples of such antibodies include antibodies against IDO, PD-L1, IL-2R, and GITR
- Known or active inflammatory bowel disease involving colon and small bowels
- Previous radiotherapy to the upper abdomen with radiation dose overlap to the involved kidney
- 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 randomisation
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy exceeding 10 mg daily dose of prednisone or equivalent or any other form of immunosuppressive therapy within 7 days prior to randomisation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: MK-3475Pembrolizumab 200 mg tobe administered as a 30 minute IV infusion every 21 days for 3 cycles | Drug | Pembrolizumab followed by SABR after cycle 1 plus nephrectomy |
| Stereotactic Ablative RadiotherapyAlso: SABR42Gy delivered in 3 fractions | Radiation | Pembrolizumab followed by SABR after cycle 1 plus nephrectomy, SABR plus nephrectomy |
| NephrectomyAlso: Surgical removal of a kidneyPartial or total nephrectomy performed 9-12 weeks after first dose of Pembrolizumab | Procedure or surgery | Pembrolizumab followed by SABR after cycle 1 plus nephrectomy, SABR plus nephrectomy |
Primary outcome
mPR post-SABR with or without pembrolizumab
Time frame: At nephrectomy performed 9-12 weeks after first dose of pembrolizumab
The mPR rate is defined as <10% residual tumour at post-nephrectomy specimens
CD8+ TRM in baseline biopsy and post-nephrectomy specimen, all measured as a continuous variable.
Time frame: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
To describe changes in tumour-responsive T-cells, TRM CD8+ T-cells from baseline to post-nephrectomy in patients treated with SABR with or without pembrolizumab treatment followed by nephrectomy
TCF-1 + tumour infiltrating lymphocytes (TILs) in baseline biopsy and post-nephrectomy specimen, measured as a continuous variable
Time frame: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
To describe changes in TCF-1+ T-cells from baseline to post-nephrectomy in patients treated with SABR with or without pembrolizumab treatment followed by nephrectomy
5 secondary outcomes
Immune response cells in baseline biopsy and post-nephrectomy specimen
Time frame: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
The tumour-responsive TRM cells inclusive of CD4+ and CD8+ compartments
Time frame: 2 weeks prior to nephrectomy
Safety of SABR with or without pembrolizumab in the neo-adjuvant setting
Time frame: 60 days post nephrectomy
Change in immune response associated with mPR
Time frame: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Change in PD-L1 and PD-L2 expression in tumour
Time frame: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shankar Siva, A/Prof study chair
Peter MacCallum Cancer Centre, Australia
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Stereotactic Ablative Radiotherapy and Nephrectomy in people with Renal Cell Carcinoma, Clear Cell, Somatic, run by Peter MacCallum Cancer Centre, Australia at 2 sites in Australia.
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 20 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shankar Siva, A/Prof (+61 3 8559 7988, Shankar.Siva@petermac.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mPR post-SABR with or without pembrolizumab (time frame: At nephrectomy performed 9-12 weeks after first dose of pembrolizumab). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 May 2024; AzTrials last refreshed its copy on 8 Nov 2026.