Pilot Study of Stereotactic Ablation for Oligometastatic Breast Neoplasia in Combination With the Anti-PD-1 Antibody MK-3475

NCT02303366 | Completed Phase 1 DMC

• 1 other identifier: Merck 3475-077
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Neoplasms; Bone Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Secondary Outcomes (4)

• Immunological Effects - Changes in immunological markers within tumor tissue, and immune subsets in peripheral blood over serial time-points, including at time of progression.

  24 months

• Treatment Effectiveness - Pain Scale. Changes in pain levels as assessed by the Numeric Pain Rating Scale.

  24 months

• Treatment Efficacy - Local Progression Free Survival (LPFS)

  24 months

• Tumor Efficacy - Distant Progression Free Survival (DPFS)

  24 months

Other Outcomes (2)

• Translational Effects - PD-L1 Expression

  24 months

• Translational Effects -Tumor Infiltrating Lymphocytes (TILs)

  24 months

Study Arms (1)

SABR + MK-3475

EXPERIMENTAL

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).

Radiation: Stereotactic Ablative Body Radiosurgery (SABR); Drug: MK-3475

Interventions

Stereotactic Ablative Body Radiosurgery (SABR) RADIATION

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

SABR + MK-3475

MK-3475 DRUG

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

Also known as: Keytruda

SABR + MK-3475

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age on day of signing informed consent.
• 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.
• 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.
• 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.
• Have a performance status of 0-2 on the ECOG Performance Scale.
• Demonstrate adequate organ function.
• Life expectancy \> 12 months.
• Be willing and able to comply with all study requirements, including treatment, attending assessments and follow-up.
• 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.
• 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.
• 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.

You may not qualify if:

• Previous high dose radiotherapy (biological equivalent of 20 Gy in 5 fractions to the area to be treated).
• Evidence of visceral metastases in liver or brain.
• 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.
• Evidence of Spinal Cord Compression.
• Spinal Instability Neoplastic Score greater than or equal to 7 unless lesion reviewed by a neurosurgical service and considered stable.
• Surgical fixation of lesion required for stability.
• Lytic metastases in a long bone (femur or humerus) that which erodes the cortex.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 8006, Australia

Location

MeSH Terms

Conditions

Breast Neoplasms; Bone Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Bone Diseases; Musculoskeletal Diseases

Study Officials

• Sherene Loi, A/Prof.

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

• Steven David, Dr

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2014
• First Posted: November 27, 2014
• Study Start: September 1, 2015
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: October 18, 2017

Record last verified: 2017-10

Locations

AU (1)