- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03988647
Palliative RT & Anti-PD-1/PD-L1 Checkpoint Blockade in Metastatic Merkel Cell Carcinoma
A Phase 2 Study of Palliative Radiation Therapy and Anti-PD-1/PD-L1 Checkpoint Blockade in Patients With Metastatic Merkel Cell Carcinoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Stanford, California, United States, 94304
- Stanford University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 1.
- 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)
- Absolute Neutrophil Count (ANC): ≥ 1000/µL (~ 1 x 109/L) Platelets: ≥ 50 x 103/µL (~ 50 x 109/L)
- Hemoglobin: ≥ 8 g/dL
- Calculated creatinine clearance greater than 30 mL/min
- Aspartate transaminase(AST)/alanine transaminase (ALT): Less than 2.5 x upper limit of normal (ULN) for subjects without liver metastasis, less than 5 times ULN for liver metastases
- Bilirubin: less than 3.0 x ULN (except for subjects with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL)
- Non-clinically significant laboratory abnormalities such as lipase elevation would not be an exclusion.
- No known active or chronic infection with HIV, Hepatitis B, or Hepatitis C, or active infection requiring systemic antibiotics. Testing for the above is not required unless clinically suspected.
- At least one measurable site of disease (≥ 10 mm as per RECIST v1.1 except for lymph nodes that must be 15 mm or greater on the short axis) outside of the planned palliative radiation therapy field.
- Require radiation therapy for palliation of symptoms or to prevent local progression of disease and associated complications and/or symptoms from metastases.
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized.
WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post-menopausal is defined as:
- Amenorrhea ≥ 12 consecutive months without another cause, or
- For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
- Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 1 week prior to the start of investigational product.
- Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized.
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.
- Bilirubin/total bilirubin 3 or more X ULN unless conjugated bilirubin is less than or equal to the ULN.
- Evidence of symptomatic interstitial lung disease or symptomatic active, noninfectious pneumonitis.
- Participants with impaired cardiac function or clinically significant cardiac disease such as unstable angina/uncompensated heart failure, uncontrolled symptomatic arrhythmia.
- Active autoimmune disease requiring systemic T-cell immunosuppression.
- Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment. This exclusion does not include prophylactic antibiotics or topical antibiotics.
- Known hypersensitivity to another monoclonal antibody, which cannot be controlled with standard measures (e.g. antihistamines and corticosteroids).
- Any condition that would, in the investigator's judgment, interfere with full participation in the study.
- Prior immune related AEs not meeting the conditions above.
- Prisoners or subjects who are involuntarily incarcerated.
- Subjects with acute or poorly controlled psychiatric illness or subjects who are compulsorily detained for physical (e.g., infectious disease) illness, with the exception of patients that are well supported and able to participate (e.g. paraplegia from a motor vehicle accident).
- Any underlying medical or psychiatric condition that, in the opinion of the investigator, could make the administration of anti-PD-1/PD-L1 hazardous or could obscure the interpretation of adverse events.
- Any live vaccine therapy for up to 4 weeks before or after any dose of immunotherapy on this trial.
- Any investigational agents within 2 weeks of scheduled first dose of pembrolizumab.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: 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
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Pembrolizumab administered at 200 mg IV every 3 weeks
Other Names:
9 Gy X 3 (27 Gy in 3 fractions), or 4-6 Gy X 5 (20-30 Gy in 5 fractions).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor Response
Time Frame: 15 months
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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.
RECIST v1.1 immune-related response will be assessed by the criterion below.
The outcome is reported as the number of lesions with each of the different levels of clinical response, a number without dispersion. |
15 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: 18 months
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Overall survival (OS) was assessed as the duration of time from study entry to time of death or the date of last contact.
The outcome is reported as OS in months.
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18 months
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Duration of Response (DOR)
Time Frame: 15 months
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The duration of response (DoR) is measured from the time the criteria are met for CR or PR (whichever is first recorded) until the date that recurrent or progressive disease is documented. 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.
RECIST immune-related response will be assessed by the criterion below.
|
15 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Susan J Knox, MD, Stanford University
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Virus Diseases
- Infections
- Neoplasms by Histologic Type
- Neoplasms
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- DNA Virus Infections
- Tumor Virus Infections
- Neuroendocrine Tumors
- Polyomavirus Infections
- Carcinoma, Neuroendocrine
- Carcinoma
- Carcinoma, Merkel Cell
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Pembrolizumab
Other Study ID Numbers
- IRB-50888 (OTHER: Stanford-IRB)
- SKIN0047 (OTHER: OnCore)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Merkel Cell Carcinoma
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National Cancer Institute (NCI)Active, not recruitingAdvanced Merkel Cell Carcinoma | Metastatic Merkel Cell Carcinoma | Pathologic Stage III Cutaneous Merkel Cell Carcinoma AJCC v8 | Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8 | Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8 | Pathologic Stage IIIA Cutaneous Merkel... and other conditionsUnited States
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National Cancer Institute (NCI)RecruitingMetastatic Merkel Cell Carcinoma | Refractory Merkel Cell Carcinoma | Locally Advanced Merkel Cell Carcinoma | Unresectable Merkel Cell Carcinoma | Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8 | Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8United States
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National Cancer Institute (NCI)CompletedRecurrent Merkel Cell Carcinoma | Stage III Merkel Cell Carcinoma AJCC v7 | Stage IV Merkel Cell Carcinoma AJCC v7 | Stage IIIA Merkel Cell Carcinoma AJCC v7 | Stage IIIB Merkel Cell Carcinoma AJCC v7United States
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University of WashingtonEMD SeronoActive, not recruitingStage III Merkel Cell Carcinoma AJCC v8 | Stage IIIB Merkel Cell Carcinoma AJCC v8 | Stage IIIA Merkel Cell Carcinoma AJCC v8United States
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedRecurrent Merkel Cell Carcinoma | Stage IV Merkel Cell CarcinomaUnited States
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National Cancer Institute (NCI)SuspendedPathologic Stage I Cutaneous Merkel Cell Carcinoma AJCC v8 | Pathologic Stage II Cutaneous Merkel Cell Carcinoma AJCC v8 | Pathologic Stage III Cutaneous Merkel Cell Carcinoma AJCC v8United States
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University of WashingtonIncyte CorporationRecruitingMerkel Cell Carcinoma | Clinical Stage IV Merkel Cell Carcinoma AJCC v8 | Unresectable Clinical Stage III Merkel Cell Carcinoma AJCC v8United States
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ImmunityBio, Inc.TerminatedStage IIIB Merkel Cell Carcinoma | Stage IV Merkel Cell CarcinomaUnited States
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); EMD SeronoTerminatedStage IV Merkel Cell Carcinoma AJCC v7 | Merkel Cell Polyomavirus InfectionUnited States
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