None listed
Conditions
Brief summary
This study will investigate the combined use of stereotactic ablative body radiosurgery (SABR) treatment followed by an investigational drug, called MK-3475, as treatment for metastatic breast cancer. Who is it for? You may be eligible to join this study if you are aged 18 years or above, diagnosed with breast cancer that has metastasised to the bones, lungs, or isolated nodes. Study details: The study aims to describe the safety profile and biological effects of combining SABR treatment with MK-3475 in patients with oligometastatic breast cancer. All participants will receive SABR treatment (one or more sessions, as required) followed by 8 cycles of MK-3475 (venous infusion, one cycle every three weeks). During each cycle, the doctor will review your general health and conduct a physical assessment as well as blood tests and a quality of life questionnaire. Radiological assessments may also be performed as necessary during and after treatment. Participants will be followed up for up to 2 years from the completion of the SABR treatment.
Interventions
Stereotactic ablative body radiotherapy (SABR) is a new form of cancer treatment involving high precision radiotherapy. Standard radiotherapy treatment is usually delivered in small doses over many treatments (usually 5 to 20 treatments). SABR treatment is different as it uses a dose of radiation delivered in 1 or 2 treatments that is much higher than standard radiotherapy dosages with the aim of destroying all cancer cells at the site of treatment. The total dose of radiation may be 5-10 times higher than standard radiotherapy doses. SABR treatment appears to be effective in controlling cancer in other sites elsewhere in the body, including the lung, kidney and the liver. We aim to test the ability of this new technique to control the cancer spots that have spread from the breast to the bones and lymph nodes and that are being treated with SABR. The investigational drug (MK-3475) is a type of monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. A monoclonal antibody is a laboratory-produced antibody that is carefully engineered to attach to your cancer cells. Monoclonal antibodies mimic the antibodies your body naturally produces as part of your immune system's response to germs, vaccines, and other invaders. There are now several approved monoclonal antibodies for the treatment of cancer or other diseases. MK-3475 is a monoclonal antibody that works against a protein called PD-1 on the surface of the cancer cells. It is thought that cancer cells with increased levels of PD-1 avoid detection by the body’s immune system. The study drug (MK-3475) is being tested to see if it can decrease the level of PD-1 in your cancer and allow the body’s immune system to identify and work against the tumour cells. 1) Screening Assessments: Initially you will be assessed to check that you are eligible to join the study. This screening period may last for a number of weeks and will involve the following procedures. A) Physical Assessment: Including height, weight, pulse rate and blood pressure assessment. You will also be asked questions about your medical history and the medicines you currently take. Finally, your doctor will assess your performance status (by asking questions about your general well-being). B) Disease Assessment: Your breast cancer will be assessed by: * Radiology scans such as a CT (computed tomography) scan of the chest, abdomen and pelvis. * Whole body bone scan * Nuclear medicine scans such as a FDG (fluorodeoxyglucose) - PET (positron emission tomography)/computed tomography (CT). * X-rays (if necessary) * Tumour Tissue: If you decide to participate in this study, your doctor will be required to send a sample of your tumour to a central laboratory, which was previously collected when you were diagnosed with metastatic breast cancer. This sample (which has already been taken from you) is currently stored in a pathology laboratory and we will request this sample to be sent to our central laboratory with your permission. If your tumour starts to grow again at a location where it is readily accessible, your doctor may propose to take a biopsy again. We would like to collect a sample of this biopsy as well to determine in which way the tumour has changed. C) Routine Blood Samples: Before entering the study, blood will be taken (approximately 15-30mls or approximately 2 tablespoons) to check for; blood cell counts, liver, pancreas, kidney and thyroid function, HIV, Hepatitis B, Hepatitis C, a breast cancer tumour marker called cancer antigen 15-3 (CA15-3), as well as a pregnancy test if you are able to become pregnant. Blood samples will be taken at every 3 weeks while treatment is continuing to monitor your haematology and serum chemistry levels. 2) STUDY TREATMENT: If you decide to participate in the study and meet the criteria to take part in the study, you will be treated according to the following schema: A) SABR TREATMENT Prior to your SABR treatment, you will be required to fill out a pain rating scale, which may take up to 2 minutes of your time. You will have either a single session of SABR treatment (20Gy in 1 fraction per area to be treated) or in some cases where there is not enough time available or for technical reasons you may be required to return for two or three sessions (i.e. You may receive 28Gy in 2 fractions). In order to deliver this treatment, you may need to attend a ‘planning CT scan’ session, where you will receive a CT scan and your body measurements are taken in the position that you will be lying in for your radiotherapy. This visit takes approximately one hour. Once the radiotherapy treatment has been planned, a further ‘mock-up’ visit may be required to ensure that the radiotherapy plan can be smoothly delivered when it comes to the time of treatment. This session will take between 45 minutes and 90 minutes. When the treatment starts, the total time required to deliver the treatment will be approximately one hour. B) MK-3475 TREATMENT MK-3475 (200mg) will be given to you by a needle in your vein (called venous infusion) over a period of 30mins, with the first dose starting a maximum of 5 days after completing SABR treatment, and delivered once every three weeks for a total of 8 cycles (i.e. 1 cycle every 3 weeks for a total of 8 cycles). Treatment with MK-3475 will continue until you have completed 6 months of treatment, or until your cancer spreads further to other parts of your body, or you experience intolerable side effects. If you stop treatment for any reason prior to completing the 6 months of MK-3475 treatment, you will be offered alternative treatment options by your study doctor. During the 6 months of MK-3475 treatment, you will be required to have a doctor’s visit every 3 weeks. Overnight stay in the hospital is not anticipated, but may become necessary. Routine blood tests, including liver, thyroid and kidney function, will be carried out during treatment at each visit before you receive MK-3475. If you develop side effects, more frequent examinations may be necessary. Your physician will document your general condition and all hospital stays during the clinical trial. He/she will similarly ask you about all side effects which you experienced and about all medications or treatments which you received since your last visit. Your doctor may suggest other tests, such as a CT scan if appropriate. The regular doctor’s visits are part of your standard medical care and are handled the same way as if you did not take part in the study. If you complete the 6 months of MK-3475 treatment and your cancer has responded, but sometime in the future your cancer returns or grows (should this happen), you will be given the option to receive a further course of MK-3475 treatment by your study doctor. 3) CLINIC VISITS/FOLLOW-UP: After your SABR treatment is completed, you will be asked to attend the hospital for a check-up at approximately 1 month, and every 3 months until two years from the date that SABR treatment was completed. Some of these visits may coincide with the 3-weekly visits required during the MK-3475 treatment, and if so, you won’t be required to come to the hospital twice. At each visit, a doctor will review your general health and whether anything new has happened to you since the last study visit (including any bad reactions or injuries), any side effect’s you may be experiencing, an assessment of how well you can perform daily activities and a review of any further anti-cancer treatments you may have undergone. At every follow-up visit, you will be expected to fill out a questionnaire to nominate your current pain rating, which will take about 2 minutes of your time. A) RADIOLOGICAL INVESTIGATIONS: The following radiological investigations will be undertaken during and after your treatment on this study: * CT Scan and Whole Body Bone Scan: You will a CT scan and whole body bone scan at 6, 12 and 24 months post end of SABR treatment unless there is evidence that your disease has progressed, in which case the scans may be done earlier.
Sponsors
Peter MacCallum Cancer Centre
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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 with the pre-screening or screening visit through to 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 a plan to receive or has received a live vaccine within 30 days prior to study treatment. 24. Has a known history of active TB (Bacillus Tuberculosis). 25. Known hypersensitivity to MK-3475 or its excipients.
Outcome results
None listed