A Phase II Study Of Pembrolizumab In Combination With Palliative Radiotherapy For Metastatic Hormone Receptor Positive Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Metastatic Breast Cancer
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Objective Response Rate
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
This research study is studying radiation therapy in combination with an immunotherapy as a possible treatment for metastatic hormone receptor (HR) positive, HER2-negative breast cancer.
The interventions involved in this study are:
- Palliative Radiotherapy
- Pembrolizumab
Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. In this research study, the investigators are evaluating the safety and effectiveness of palliative radiotherapy ("radiation therapy") in combination with pembrolizumab in HR-positive, HER2-negative breast cancer. This study is designed to test how well radiation therapy in combination with pembrolizumab treats this type of cancer. The FDA has approved radiation therapy as a treatment option for this type of breast cancer. The FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for this specific disease but it has been approved in the United Sates for other types of cancer. Pembrolizumab is a drug that may treat cancer by working with the immune system. The immune system is the body's natural defense against disease. The immune system sends types of cells called "T cells" throughout the body to detect and fight infections and diseases, including cancer. For some types of cancer, the T cells do not work as they should and are prevented from attacking the tumors. Pembrolizumab is thought to work by blocking a protein in the T cells called PD-1 ("programmed death 1"), which then allows these cells and other parts of the immune system to attack tumors. The combination of pembrolizumab and radiation therapy is investigational. The study drug and radiation therapy, when given separately, work in different waysto help stop the cancer cells from growing and spreading. However, it is not known if giving the study drug and radiation therapy at the same time will have a better anti-cancer effect than giving each treatment on its own.
Investigators
Sara Tolaney
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •Participants must have histologically or cytologically confirmed invasive breast cancer, with metastatic disease. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
- •Invasive disease must have been tested for ER, PR and HER
- •Participants must have hormone-receptor positive, HER2-negative breast cancer defined as:
- •ER\>1% or PR\>1%
- •HER2-negative per ASCO CAP guidelines, 2013 \[Wolff et al., 2013\]
- •Participant must be a candidate for palliative radiation treatment to at least one bone, lymph node, or soft tissue lesion. Radiation of visceral lesions (such as lung or hepatic lesions) is not permitted.
- •Participant must have measurable disease outside the field of radiation as defined by RECIST 1.
- •If tumor is accessible and outside the field of radiation, the participant must be willing to undergo a research biopsy at baseline and after 2 cycles of pembrolizumab. Participants for whom newly-obtained samples cannot be provided (e.g. inaccessible or safety concern) must be willing to submit an archival specimen.
- •Prior systemic therapy:
- •Participant must be at least 14 days from the last dose of prior chemotherapy, endocrine therapy, biological agents (including small molecule targeted therapy) or any investigational drug product with adequate recovery of toxicity to baseline, or grade 1(with the exception of alopecia and hot flashes) at the time of registration.
Exclusion Criteria
- •Participants who are receiving any other investigational agents.
- •Previous treatment with any anti-PD-1, PD-L1, or PD-L2 agent.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab.
- •Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with previously diagnosed brain metastases are eligible if they have:
- •completed treatment (whole brain radiotherapy, radiosurgery, or a combination) at least 3 months prior to trial therapy initiation,
- •are neurologically stable, and
- •have recovered from effects of radiotherapy or surgery. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥2 weeks before prior to registration.
- •Radiologic or clinical evidence of Spinal Cord Compression.
- •Spinal Instability Neoplastic Score ≥ 7 unless lesion reviewed by a neurosurgical service and considered stable.
- •Participants with bone lesions requiring surgical fixation to provide mechanical stability are ineligible. Participants with previously fixed lesions are allowed.
Arms & Interventions
Pembrolizumab With Radiation
pembrolizumab : 200 mg intravenously 2 to 7 days prior to radiotherapy (RT) and on day 1 of repeating 21-day cycles. Treatment up to 35 cycles. Palliative radiation: a total dose of 20 Gy in 5 fractions
Intervention: Pembrolizumab
Pembrolizumab With Radiation
pembrolizumab : 200 mg intravenously 2 to 7 days prior to radiotherapy (RT) and on day 1 of repeating 21-day cycles. Treatment up to 35 cycles. Palliative radiation: a total dose of 20 Gy in 5 fractions
Intervention: Palliative radiotherapy
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: Tumor measurements are repeated every 6 weeks for the first 24 weeks and then every 9 weeks thereafter. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was 1 cycle. Response was evaluated up to 3 months.
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) outside the field of radiation based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcomes
- Median Progression-free Survival (PFS)(Tumor measurements are repeated every 6 weeks for the first 24 weeks and then every 9 weeks thereafter. Treatment continued until disease progression or unacceptable toxicity. The maximum follow-up time is 3 months.)
- Median Overall Survival (OS)(Tumor measurements are repeated every 6 weeks for the first 24 weeks and then every 9 weeks thereafter. Treatment continued until disease progression or unacceptable toxicity. The maximum follow-up time is 13 months.)
- Incidence of Grade 4 Treatment-Related Toxicity(Tumor measurements are repeated every 6 weeks for the first 24 weeks and then every 9 weeks thereafter. Treatment continued until disease progression or unacceptable toxicity. Response was evaluated up to 3 months.)