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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02855203




Registration number
NCT02855203
Ethics application status
Date submitted
28/07/2016
Date registered
4/08/2016
Date last updated
16/08/2018

Titles & IDs
Public title
Stereotactic Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) for Oligometastatic Renal Tumours
Scientific title
Stereotactic Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) for Oligometastatic Renal Tumours
Secondary ID [1] 0 0
15/143
Universal Trial Number (UTN)
Trial acronym
RAPPORT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Stereotactic Ablative Body Radiosurgery (SABR)
Treatment: Drugs - Pembrolizumab

Experimental: SABR + Pembrolizumab - SABR treatment (18Gy-20Gy/1#) followed by 200mg pembrolizumab IV once every 3 weeks for a total of 8 cycles


Treatment: Other: Stereotactic Ablative Body Radiosurgery (SABR)
18-20Gy in 1 fraction

Treatment: Drugs: Pembrolizumab
Pembrolizumab at a dose of 200mg IV, 3-weekly will be delivered for a duration of 6 months, commencing 5 days (+/- 3 days) from the last dose of SABR.

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Toxicities measured using CTCAE version 4.03
Timepoint [1] 0 0
Up to 24 months after SABR treatment
Secondary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
From start of treatment until the date of death from any cause assessed up to the date when the last patient has their 12 months assessment
Secondary outcome [2] 0 0
Time to local progression (TTLP)
Timepoint [2] 0 0
From start of treatment until the date of first local progression or until the date of death from any cause, whichever occurs first, assessed up to the date when the last patient has their 12 months assessment
Secondary outcome [3] 0 0
Distant progression free survival (DPFS)
Timepoint [3] 0 0
From start of treatment until the date of first distant progression or until the date of death from any cause, whichever occurs first, assessed up to the date when the last patient has their 12 months assessment
Secondary outcome [4] 0 0
Overall response assessed using RECIST 1.1
Timepoint [4] 0 0
Assessed at 3, 6, 12 and 24 months
Secondary outcome [5] 0 0
Pain assessed using the Numerical Pain Rating Scale
Timepoint [5] 0 0
Assessed 3-monthly until 24 months after end of SABR treatment

Eligibility
Key inclusion criteria
1. Has provided written informed consent for the trial.

2. Be at least 18 years of age on day of signing informed consent.

3. Have oligometastases (1-5 metastases), and measurable disease based on RECIST 1.1.

4. Participants must have a histologically or cytologically confirmed metastatic renal
cell carcinoma. Oligometastatic lesions do not need to be biopsied but they must be
clinically consistent to represent metastatic disease.

5. Patient can either be treatment naïve or have previously received up to 2 lines of
systemic treatment (eg. Pazopanib or Sunitinib). The total number of metastases
throughout the pre-trial period should not number more than 5.

6. Must have had surgical consideration for metastasectomy and thought appropriate for
SABR due to medical inoperability, technical factors or patient declining surgery.

7. Must have at least one metastasis for which SABR is technically deliverable.

8. Be willing to provide archival tissue from a previously biopsied or excised primary or
metastatic RCC lesion (if available). If safe to do so, a request for newly obtained
specimen (obtained up to 4 weeks prior to initiation of treatment) will be made,
however participation for this biopsy is entirely optional.

9. Have a performance status of 0-2 on the ECOG Performance Scale

10. Demonstrate adequate organ function as defined below all screening labs should be
performed within 10 days of registration.

- Absolute neutrophil count (ANC) - =1.5 X 10^9/L

- Platelets - =100 X 10^9/L

- Hemoglobin - =90 g/L or =5.6 mmol/L without transfusion or EPO dependency (within
7 days of assessment)

- Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be
used in place of creatinine or CrCl) - =1.5 X upper limit of normal (ULN) OR =60
mL/min for participant with creatinine levels > 1.5 X institutional ULN

- Serum total bilirubin - = 1.5 X ULN OR Direct bilirubin = ULN for participants
with total bilirubin levels > 1.5 ULN

- AST (SGOT) and ALT (SGPT) - = 2.5 X ULN OR = 5 X ULN for participants with liver
metastases

- Albumin - >2.5 mg/dL

- International Normalized Ratio (INR) or Prothrombin Time (PT) - =1.5 X ULN unless
participant is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants

- Activated Partial Thromboplastin Time (aPTT) - =1.5 X ULN unless participant is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
of intended use of anticoagulants

11. Life expectancy > 12 months.

12. Be willing and able to comply with all study requirements, including treatment,
attending assessments and follow-up.

13. Female participant of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.

14. Female participants of childbearing potential should be willing to use 2 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 (see
Section 9.4.2: Contraception). Participants of childbearing potential are those who
have not been surgically sterilized or have not been free from menses for > 1 year.

15. Male participants 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Based on clinician assessment of disease volume and rate of progression of patient's
tumor deposits, the patient requires immediate TKI therapy.

2. Has had previous high dose radiotherapy (biological equivalent of 30Gy in 10#) to an
area to be treated which includes vertebral bodies (see below).

Note: Previous high dose radiotherapy is defined as a biological equivalent dose to
above that of 30 Gy in 10 fractions using an alpha/beta ratio [82] of 3. Where a
patient has received radiotherapy to an equivalent or lower dose than defined above,
stereotactic radiotherapy of the area may be considered. In doing so, assessment of
the volume and total dose received by any overlap region must be made, and documented
by generating a cumulative plan incorporating both the previous and current treatment
fields. It is the treating radiation oncologist's responsibility to review both the
current plan and the cumulative plan inclusive of previous radiotherapy.

3. Has evidence of untreated or active intracranial metastases. Patients who have had
fully resected brain metastasis or those controlled by stereotactic radiotherapy are
eligible as long as they are not requiring corticosteroids for symptomatic control.

4. Has evidence of Spinal Cord Compression.

5. Has a Spinal Instability Neoplastic Score = 7 unless lesion reviewed by a
neurosurgical service and considered stable (see Appendix 3).

6. Requires surgical fixation of bone lesion for stability. This must be performed before
enrollment into the trial.

7. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days of registration.

8. Has a known history of active TB (Bacillus Tuberculosis).

9. Hypersensitivity to pembrolizumab or any of its excipients.

10. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks of registration
or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to
agents administered more than 4 weeks earlier.

11. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks of registration or who has not recovered (i.e., = Grade 1 or at
baseline) from adverse events due to a previously administered agent.

Note: Participants with = Grade 2 neuropathy are an exception to this criterion and
may qualify for the study.

Note: If participant received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting therapy.

12. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.

13. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Participants with previously treated brain metastases may participate
provided they are stable (without evidence of progression by imaging for at least four
weeks prior to the first dose of trial treatment and any neurologic symptoms have
returned to baseline), have no evidence of new or enlarging brain metastases, and are
not using steroids within 7 days of registration. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability.

14. 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 (e.g. thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.

15. Has known history of, or any evidence of active, non-infectious pneumonitis.

16. Has an active infection requiring systemic therapy.

17. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the participant's
participation for the full duration of the trial, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator.

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

19. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.

20. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

21. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

22. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).

23. Has received a live vaccine within 30 days of registration

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Single group
Other design features
Phase
Phase 1/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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
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
Olivia Newton- John Cancer Centre - Heidelberg
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg

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

Ethics approval
Ethics application status

Summary
Brief summary
This investigator driven study will examine the safety, efficacy and biological effects of
combining pembrolizumab (MK-3475) an antibody targeted against anti-programmed cell death 1
(PD-1), with stereotactic ablative body radiotherapy (SABR) for oligometastatic renal cell
carcinoma (RCC). The investigators hypothesise that the safety profile of this combination
will be clinically acceptable.
Trial website
https://clinicaltrials.gov/show/NCT02855203
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Shankar Siva, Dr
Address 0 0
Country 0 0
Phone 0 0
+61 3 8559 5000
Fax 0 0
Email 0 0
Shankar.Siva@petermac.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02855203