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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03307759




Registration number
NCT03307759
Ethics application status
Date submitted
6/10/2017
Date registered
12/10/2017
Date last updated
19/12/2018

Titles & IDs
Public title
Sequencing of Stereotactic Ablative Body Radiotherapy in Combination With PD-1 Blockade Using Pembrolizumab in Metastatic Non-Small Cell Lung Carcinoma
Scientific title
Sequencing of Stereotactic Ablative Body Radiotherapy in Combination With PD-1 Blockade Using Pembrolizumab in Metastatic Non-Small Cell Lung Carcinoma
Secondary ID [1] 0 0
SABRseq
Universal Trial Number (UTN)
Trial acronym
SABRseq
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab
Treatment: Other - Radiotherapy (SABR)

Active Comparator: SABR plus pembrolizumab - SABR followed by pembrolizumab

Active Comparator: Pembrolizumab plus SABR - Pembrolizumab followed by SABR after cycle 1


Treatment: Drugs: Pembrolizumab
Pembrolizumab

Treatment: Other: Radiotherapy (SABR)
Radiotherapy

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

Outcomes
Primary outcome [1] 0 0
Adverse events measured using CTCAE version 4.03
Timepoint [1] 0 0
Up to 24 months after commencement of treatment
Secondary outcome [1] 0 0
Overall response assessed using RECIST 1.1
Timepoint [1] 0 0
Assessed at 6 and 12 months
Secondary outcome [2] 0 0
Overall response assessed using irRECIST
Timepoint [2] 0 0
Assessed at 6 and 12 months
Secondary outcome [3] 0 0
Overall response assessed using PERCIST1.0
Timepoint [3] 0 0
Assessed at 6 and 12 months
Secondary outcome [4] 0 0
Overall response assessed using Peter Mac Metabolic Response Criteria
Timepoint [4] 0 0
Assessed at 6 and 12 months
Secondary outcome [5] 0 0
Overall survival
Timepoint [5] 0 0
From randomisation until the date of death from any cause assessed up to the date when the last patient has their 24 months assessment
Secondary outcome [6] 0 0
Progression free survival (PFS)
Timepoint [6] 0 0
From randomisation until the date of first progression or until the date of death from any cause, whichever occurs first, assessed up to the date when the last patient has their 24 months assessment

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

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

3. Have at least one lesion not planned for SABR that is measurable disease based on
RECIST 1.1.

4. Patients must have a histologically or cytologically confirmed metastatic non-small
cell lung cancer.

5. Patients with disease previously untreated with systemic therapy must have = 50% PD-L1
staining and patients who have previously received systemic therapy must have = 1%
PD-L1 staining on immunohistochemistry

6. Patients must have at least 1-3 lesions suitable for treatment with stereotactic
radiotherapy.

7. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumour lesion where feasible. Newly-obtained is defined as a specimen obtained up to
12 weeks prior to randomisation. Patients for whom newly-obtained samples cannot be
provided (e.g. inaccessible or patient safety concern) may submit an archived specimen
only upon agreement from the study principal investigators.

8. Have a performance status of 0-1 on the ECOG Performance Scale (see Appendix 1).

9. Demonstrate adequate organ function as defined in table 3 below, all screening labs
should be performed within 10 days of randomisation.

Table 3 Adequate Organ Function Laboratory Values

Absolute neutrophil count (ANC) =1.5x109/L Platelets=100x109L Haemoglobin =90 g/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 =30 mL/min for
patients with creatinine levels > 1.5 X institutional ULN

Serum total bilirubin = 1.5 X ULN OR Direct bilirubin = ULN for patients with total
bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT)= 2.5 X ULN OR = 5 X ULN for
patients with liver metastases

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

10. Life expectancy > 3 months.

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

12. Female patient of childbearing potential should have a negative urine or serum
pregnancy within 7 days of randomisation. If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required.

13. Female patients 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
8.10). Patients of childbearing potential are those who have not been surgically
sterilized or have not been free from menses for > 1 year.

14. 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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 (50) 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.

2. Has had previous thoracic radiotherapy of > 36Gy within the 6 months prior to
randomisation.

3. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with small asymptomatic or 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 enlarging brain metastases,
and are not using steroids for intracranial neurological symptoms at least 7 days
prior to trial randomisation. This exception does not include leptomeningeal disease
which is excluded regardless of clinical stability.

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 2).

6. Requires surgical fixation of bone lesion for stability. All surgical fixation and
instrumentation must be completed before randomisation on study.

7. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of randomisation.

8. Has a diagnosis of immunodeficiency.

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

10. Has a hypersensitivity to pembrolizumab or any of its excipients.

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

12. Has diagnosed and/or treated additional malignancy within 5 years prior to
randomisation with the exception of: curatively treated basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, curatively treated early stage cervical
cancer, breast cancer or prostate cancer with no evidence of active disease. Other
exceptions may be considered following consultation with the principal investigator

13. 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.

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

15. Has had any systemic anti-cancer therapy or radiation therapy within 4 weeks prior to
randomisation

16. Has known interstitial lung disease

17. Has an active infection requiring systemic therapy.

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

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

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 randomisation. Note: Seasonal influenza
vaccines for injection are generally inactivated flu vaccines and are allowed; however
intranasal influenza vaccines (e.g., Flu- Mist®) are live attenuated vaccines, and are
not allowed. -

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 1
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)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Ontario

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 Phase Ib study will examine the safety, efficacy and biological
effects of two schedules of pembrolizumab, an antibody targeted against anti-programmed cell
death 1 (PD-1), which will be given either before or after stereotactic ablative body
radiotherapy (SABR) for metastatic NSCLC.
Trial website
https://clinicaltrials.gov/show/NCT03307759
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, MBBS FRANZCR
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/NCT03307759