A Phase 2 Study of Palliative Radiation Therapy and Anti-PD-1/PD-L1 Checkpoint Blockade in Patients With Metastatic Merkel Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Merkel Cell Carcinoma
- Sponsor
- Stanford University
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- Tumor Response
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
The primary objectives of this study are to assess 1) the safety and 2) efficacy of combining Anti-PD-1/PD-L1 blockade with palliative radiation therapy in patients with Stage IV Merkel Cell Carcinoma.
Detailed Description
The hypothesis for this study is that local radiation therapy (RT) can be safely used in combination with PD-1/PD-L1 blockade. This combination therapy may have the potential to enhance the induction of systemic anti-Merkel cell carcinoma immune responses, which will inhibit growth and kill Merkel cell tumor cells in sites of established metastases outside of the local radiation therapy field.
Investigators
Susan Pillsbury
Associate Professor of Radiation Oncology
Stanford University
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed metastatic Merkel Cell Carcinoma.
- •Patients are eligible if they have received no more than 3 prior systemic treatments, inclusive of systemic adjuvant therapy. This includes previously untreated patients.
- •Subjects with brain metastases and/or carcinomatous meningitis are eligible providing they are neurologically stable (if systemic steroids are required, subjects should be stable on the lowest clinically effective dose, as steroids may interfere with the activity of immunotherapy if administered at the time of the first Anti-PD-1/PD-L1 dose.)
- •Availability of tumor tissue (fresh or archival) for central pathology review.
- •Must be at least 14 days since treatment with chemotherapy, biochemotherapy, surgery, or immunotherapy, and recovered (baseline or residual Grade 1 toxicity) from any clinically significant toxicity experienced during treatment before the first dose of pembrolizumab therapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy of ≥ 16 weeks.
- •Subjects must have measurable disease according to RECIST v1.1, and have baseline (screening/baseline) radiographic images, (e.g. CT, Positron emission tomography (PET)/CT or MRI brain, chest, abdomen, pelvis, to be determined by the attending physician) within 4 weeks of confirmation of eligibility and within 6 weeks before the initiation of pembrolizumab therapy.
- •Required values for initial laboratory tests:
- •White blood cells (WBC): ≥ 2000/µL (\~ 2 x 109/L)
Exclusion Criteria
- •WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 26 weeks after the last dose of investigational product.
- •Women who are pregnant or breastfeeding.
- •Women with a positive pregnancy test on enrollment or before investigational product administration.
- •Subjects on any other systemic therapy for cancer, including any other experimental treatment within 2 weeks of scheduled first dose of pembrolizumab.
- •Prior treatment with an anti-PD-1/PD-L1 antibody if treatment failure was due to AEs. If a subject was discontinued from the prior anti-PD-1/PD-L1 treatment due to an Adverse events (AE) or Serious adverse events (SAE), regardless of the type of event, that discontinuation constitutes an exclusion criterion. If AEs were serious enough to require a subject's withdrawal from prior treatment, the subject should be excluded from this study. The exception to the above are non-clinically significant immune-related laboratory abnormalities - these are not automatic exclusions - e.g. asymptomatic elevated amylase; responsiveness to steroids. In situations above - e.g. non-clinically significant immune-related laboratory abnormalities, each case will be considered individually and a decision made by the study team.
- •A history of AEs with prior IL-2 or Interferon will not preclude subjects from entering the current study.
- •Autoimmune disease: Poorly controlled autoimmune disease is excluded. Well controlled autoimmune disease (e.g. well controlled RA) will be assessed by the study team and a decision made regarding eligibility based on the degree of immunosuppression and severity of symptoms.
- •Any subject who has a life-threatening condition that requires high-dose immunosuppressant(s). Steroid doses greater than 20 mg/day will exclude the patient from participation in the trial.
- •Presence of known hepatitis B or hepatitis C infection, regardless of control on antiviral therapy.
- •Subjects who have another active, concurrent, malignant disease are not eligible, with the exception of subjects with adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or other cancers that are in remission/not measurable. Patients will be excluded if they have any known additional malignancy that requires active treatment while on treatment for Merkel Cell Carcinoma.
Arms & Interventions
Pembrolizumab + Palliative Radiation Therapy
Pembrolizumab will be administered at 200 mg IV every 3 weeks as standard of care. Palliative radiation therapy will be given between the first and second cycles of immunotherapy
Intervention: Pembrolizumab
Pembrolizumab + Palliative Radiation Therapy
Pembrolizumab will be administered at 200 mg IV every 3 weeks as standard of care. Palliative radiation therapy will be given between the first and second cycles of immunotherapy
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
Tumor Response
Time Frame: 15 months
Tumor Response at both irradiated \& unirradiated sites will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Basic RECIST response will be assessed by the criterion below. * Complete Response (CR) = Disappearance of all target lesions. * Partial Response (PR) = ≥0% decrease in the sum of the longest diameter (LD) of target lesions. * Stable disease (SD) = Small changes that do not meet any of the above criteria. RECIST v1.1 immune-related response will be assessed by the criterion below. * Immune-related CR (irCR) = Disappearance of all target lesions. Lymph nodes \<10 mm in short axis. * Immune-related PR (irPR) = ≥30% decrease in the sum of the LD of target lesions. * Immune-related SD (irSD) = Failure to meet criteria for irCR or irPR in the absence of irPR. The outcome is reported as the number of lesions with each of the different levels of clinical response, a number without dispersion.
Secondary Outcomes
- Duration of Response (DOR)(15 months)
- Overall Survival (OS)(18 months)