A pilot study of patients with oligometastases from breast cancer treated with stereotactic ablative body radiosurgery in combination with the anti-PD-1 antibody MK-3475.

Phase 1

Recruiting

• Conditions: Metastatic Breast Cancer (1-5 metastases); Cancer - Breast; Cancer - Bone

• Registration Number: ACTRN12614001181695
• Lead Sponsor: Peter MacCallum Cancer Centre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-11-11
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 15

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.

Exclusion Criteria

1. Previous high dose radiotherapy (BED > 20Gy) to an area to be treated which includes vertebral bodies.
2. Evidence of brain metastases.
3. Intention to treat with any chemotherapy agent within +/- 3 weeks of study treatment.
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. A dose of 28Gy in 2 fractions can be considered after review at SABR chart round.
6. Surgical fixation of bone lesion required for stability.
7. Lytic metastases in a long bone (femur or humerus) that erodes the cortex.
8. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and is planned to receive study therapy or used an investigational device within 4 weeks of study treatment.
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy at time of study registration.
10. Has a plan to receive or did receive a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study treatment or has not recovered from adverse events (i.e. AEs not at = Grade 1 or at baseline values) due to agents administered more than 4 weeks earlier.
11. Is planned to receive chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study treatment or who has not recovered from adverse events (i.e. AEs not at = Grade 1 or at baseline values) due to a previously administered agent.
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. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to study registration and any neurological 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. 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 (eg., 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 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.
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 w

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary objective is to determine the safety profile of stereotactic ablative body radiosurgery (SABR) in combination with MK-3475 treatment in patients with oligometastatic breast cancer.[Safety will be evaluated using CTCAE version 4.0 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. AE assessments will be conducted from time of study consent, during treatment, at 1 month post end of treatment, and at every 3 months until 2 years from the date that SABR was completed.]