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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02303366




Registration number
NCT02303366
Ethics application status
Date submitted
25/11/2014
Date registered
27/11/2014
Date last updated
18/10/2017

Titles & IDs
Public title
Pilot Study of Stereotactic Ablation for Oligometastatic Breast Neoplasia in Combination With the Anti-PD-1 Antibody MK-3475
Scientific title
A Pilot Study of Stereotactic Ablation for Oligometastatic Breast Neoplasia in Combination With the Anti-PD-1 Antibody MK-3475.
Secondary ID [1] 0 0
Merck 3475-077
Universal Trial Number (UTN)
Trial acronym
BOSTON II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Neoplasms 0 0
Bone Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Stereotactic Ablative Body Radiosurgery (SABR)
Treatment: Drugs - MK-3475

Experimental: SABR + MK-3475 - SABR treatment (20Gy in 1 fraction) to at least one metastases (to a maximum of 5 metastases) followed by 8 cycles of 3 weekly treatment with MK-3475 (200mg IV per dose).


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

Treatment: Drugs: MK-3475
MK-3475 (200mg IV) on day 1 every 3 weeks for a total of 8 cycles.

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
Safety Profile - Summary of acute and long term adverse events as assessed by CTCAE v4.0 - Safety profile will be evaluated using CTCAE v4.0 in all patients who have received at least one SABR treatment and one dose of MK-3475. Acute AE are defined as AE's occurring from the time from 1st SABR treatment to 30 days post end of MK-3475 treatment and long term AE are defined as AE's occurring after 30 days post end of MK-3475 treatment.
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
Immunological Effects - Changes in immunological markers within tumor tissue, and immune subsets in peripheral blood over serial time-points, including at time of progression. - Blood samples will be collected (50ml) at baseline (prior to first SABR), prior to the first dose of MK-3475, prior to cycle 2 of MK-3475, at disease progression (if this occurs) and then every 3 months up to two years post end of SABR treatment. These will be analysed for the following (this is a non-exhaustive list):
i. Absolute lymphocyte counts using a blood analyser.
ii. The presence of CD8+ T cells by flow cytometric analysis.
iii. Change in frequency of tumor reactive T cells. These may include markers for HLA-DR, CD4+, CD8+ T cells, PD-1, TIM-3 signifying antigen presentation and experience.
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Treatment Effectiveness - Pain Scale. Changes in pain levels as assessed by the Numeric Pain Rating Scale. - Pain levels will be evaluated pre and post-treatment using the Numerical Rating Pain Scale at the following time points: pre-SABR treatment, at approximately 1 month, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and at 24 months after the end of SABR treatment.
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Treatment Efficacy - Local Progression Free Survival (LPFS) - LPFS will be assessed at baseline, 1 month post SABR treatment, then at every three months for 24 months or until the date of first local progression, or date of death for patients without local progression.
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Tumor Efficacy - Distant Progression Free Survival (DPFS) - DPFS will be assessed at baseline, 1 month post SABR treatment, then at every three months for 24 months or until the date of first local progression, or date of death for patients without distant progression.
Timepoint [4] 0 0
24 months

Eligibility
Key inclusion criteria
1. Be willing and able to provide written informed consent/assent for the trial.

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

3. Have histologically or cytologically confirmed breast cancer. Oligometastatic lesions
do not need to be biopsied but they must be strongly suspected to represent metastatic
disease.

4. CT scan (Chest, Abdo + Pelvis), Whole Body Bone scan, and FDG-PET scan evidence of 1
to 5 metastases within 8 weeks of study registration.

Note: At least 1 of the 5 metastases must be deemed suitable for SABR treatment.

5. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumour lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42
days) prior to initiation of treatment on Day 1. Participants for whom newly-obtained
samples cannot be provided (e.g. inaccessible or participant safety concern) may
submit an archived specimen only upon agreement from the study P.I's.

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

7. Demonstrate adequate organ function.

8. Life expectancy > 12 months.

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

10. Female patients of childbearing potential must have a negative urine or serum
pregnancy within 7 days of study registration and re-tested 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.

11. Female patients of childbearing potential must 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 to 120 days after the last dose of MK-3475. Patients of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year.

12. Male patients must agree to use an adequate method of contraception starting with the
first SABR treatment, through to 120 days after the last dose of MK-3475.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous high dose radiotherapy (biological equivalent of 20 Gy in 5 fractions to the
area to be treated).

2. Evidence of visceral metastases in liver or brain.

3. Treatment with any chemotherapy agent within +/- 3 weeks of SABR. Targeted therapy or
endocrine therapy is permitted at any stage during the conduct of this study, however
is not to be changed during the study period unless due to progression.

4. Evidence of Spinal Cord Compression.

5. Spinal Instability Neoplastic Score greater than or equal to 7 unless lesion reviewed
by a neurosurgical service and considered stable.

6. Surgical fixation of lesion required for stability.

7. Lytic metastases in a long bone (femur or humerus) that which erodes the cortex.

8. Is currently participating in or has participated in a study of an investigational
agent or using an investigational device within 4 weeks of the first dose of
treatment.

9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior to the first dose
of trial treatment. Single once of doses are acceptable.

10. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not
recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due
to agents administered more than 4 weeks earlier. Patients must not be receiving
denosumab on this study.

11. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 3 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal
to Grade 1 or at baseline) from adverse events due to a previously administered agent.

Note: Subjects with less than or equal to Grade 2 neuropathy are an exception to this
criterion and may qualify for the study.

Note: If subject 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, squamous cell carcinoma of the
skin, or in situ cervical cancer that has undergone potentially curative therapy.

13. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects 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 for at least 7 days prior to trial treatment.

14. Has an active automimmune disease requiring systemic treatment within the past 3
months or a documented history of clinically severe autoimmune disease, or a syndrome
that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or
resolved childhood asthma/atopy would be an exception to this rule. Subjects that
require intermittent use of bronchodilators or local steroid injections would not be
excluded from the study. Subjects with hypothyroidism stable on hormone replacement or
Sjorgen's syndrome will not be excluded from the study.

15. Has evidence of interstitial lung disease or 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 subject's
participation for the full duration of the trial, or is not in the best interest of
the subject 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 pre-screening or 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, anti-PD-L2, anti-CD137, or
anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
or checkpoint pathways).

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 prior to the first dose of trial treatment.

24. Known active tuberculosis

25. Known hypersensitivity to Pembrolizumab or its exicipients

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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
8006 - 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, observational pilot study that will describe the safety profile and
biological effects of combining stereotactic ablative body radiosurgery (SABR) treatment
(20Gy/1#) and a PD-1 antibody, MK-3475.

15 patients with oligometastatic breast cancer with at least one lesion considered safe for
SABR radiotherapy, will be treated with SABR for their oligometatastic disease in addition to
6 months of MK-3475 treatment (1 cycle every 3 weeks, a total of 8 cycles).

This investigator driven pilot study will examine the safety and biological effects of
combining MK-3475 (Pembrolizumab) an antibody targeted against the anti-programmed cell death
1 (PD-1) T cell checkpoint, with SABR therapy for oligometastatic disease. We hypothesise
that the safety profile of this combination, will be clinically acceptable and well tolerated
for patients, and that we will observe evidence of systemic immune activation.
Trial website
https://clinicaltrials.gov/show/NCT02303366
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sherene Loi, 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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications