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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05024318




Registration number
NCT05024318
Ethics application status
Date submitted
29/03/2021
Date registered
27/08/2021
Date last updated
16/05/2024

Titles & IDs
Public title
NeoAdjuvant Pembrolizumab and STEreotactic Radiotherapy Prior to Nephrectomy for Renal Cell Carcinoma
Scientific title
NeoAdjuvant Pembrolizumab and STEreotactic Radiotherapy Prior to Nephrectomy for Renal Cell Carcinoma: Investigating Induced Immune Context Changes
Secondary ID [1] 0 0
19/007
Universal Trial Number (UTN)
Trial acronym
NAPSTER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma, Clear Cell, Somatic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab
Treatment: Other - Stereotactic Ablative Radiotherapy
Treatment: Surgery - Nephrectomy

Active Comparator: SABR plus nephrectomy - 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.

Experimental: Pembrolizumab followed by SABR after cycle 1 plus nephrectomy - 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.


Treatment: Drugs: Pembrolizumab
Pembrolizumab 200 mg tobe administered as a 30 minute IV infusion every 21 days for 3 cycles

Treatment: Other: Stereotactic Ablative Radiotherapy
42Gy delivered in 3 fractions

Treatment: Surgery: Nephrectomy
Partial or total nephrectomy performed 9-12 weeks after first dose of Pembrolizumab
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
mPR post-SABR with or without pembrolizumab
Timepoint [1] 0 0
At nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Primary outcome [2] 0 0
CD8+ TRM in baseline biopsy and post-nephrectomy specimen, all measured as a continuous variable.
Timepoint [2] 0 0
Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Primary outcome [3] 0 0
TCF-1 + tumour infiltrating lymphocytes (TILs) in baseline biopsy and post-nephrectomy specimen, measured as a continuous variable
Timepoint [3] 0 0
Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Secondary outcome [1] 0 0
Immune response cells in baseline biopsy and post-nephrectomy specimen
Timepoint [1] 0 0
Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Secondary outcome [2] 0 0
The tumour-responsive TRM cells inclusive of CD4+ and CD8+ compartments
Timepoint [2] 0 0
2 weeks prior to nephrectomy
Secondary outcome [3] 0 0
Safety of SABR with or without pembrolizumab in the neo-adjuvant setting
Timepoint [3] 0 0
60 days post nephrectomy
Secondary outcome [4] 0 0
Change in immune response associated with mPR
Timepoint [4] 0 0
Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Secondary outcome [5] 0 0
Change in PD-L1 and PD-L2 expression in tumour
Timepoint [5] 0 0
Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab

Eligibility
Key inclusion criteria
1. Patient has provided written informed consent

2. Male or female aged 18 years or older at written informed consent

3. Histologically or cytologically confirmed diagnosis of RCC with clear cell, rhabdoid
or sarcomatoid components

4. Tumour stage T1B-T3, N0 or N1, M0 or low volume M1 planned for nephrectomy

5. 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

- 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

6. ECOG performance status of 0 or 1

7. 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

8. 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

9. 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

10. Patient agrees to the collection and use of their fresh tumour samples and peripheral
blood for translational research

11. 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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

2. Known or active inflammatory bowel disease involving colon and small bowels

3. Previous radiotherapy to the upper abdomen with radiation dose overlap to the involved
kidney

4. 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

5. 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

6. 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

7. 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

8. 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

9. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients

10. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis

11. Has an active infection requiring systemic therapy

12. Has a known history of HIV infection

13. 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

14. 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

15. Has a known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial

16. 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

17. Has had a prior solid organ transplant

18. 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.

19. Any contraindications for surgery

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2025
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 carcinoma (ccRCC).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05024318
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Shankar Siva, A/Prof
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Shankar Siva, A/Prof
Address 0 0
Country 0 0
Phone 0 0
+61 3 8559 7988
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05024318