Merkel Cell CarcinomaPhase 2NCT03988647
Palliative RT & Anti-PD-1/PD-L1 Checkpoint Blockade in Metastatic Merkel Cell Carcinoma
A Phase 2 study testing Pembrolizumab and Radiation Therapy in people with Merkel Cell Carcinoma, run by Stanford University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Merkel Cell Carcinoma
- What is being tested?
- Pembrolizumab and Radiation Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jul 2019to 20 Jan 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Study of Palliative Radiation Therapy and Anti-PD-1/PD-L1 Checkpoint Blockade in Patients With Metastatic Merkel Cell Carcinoma
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.
Read the 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.
- Conditions
- Merkel Cell Carcinoma
- Being tested
- Pembrolizumab, Radiation Therapy
- Medical subject headings
- Carcinoma, Merkel Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab administered at 200 mg IV every 3 weeks
Radiation TherapyRadiation
9 Gy X 3 (27 Gy in 3 fractions), or 4-6 Gy X 5 (20-30 Gy in 5 fractions).
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Palliative Radiation Therapy | Experimental | 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 Receives: Drug: Pembrolizumab; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Response
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.
Measured: 15 months
Secondary outcomes (2)
Overall Survival (OS)
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.
Measured: 18 months
Duration of Response (DOR)
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.
- CR = Disappearance of all target lesions.
- PR = ≥0% decrease in the sum of the longest diameter (LD) of target lesions.
- SD = Small changes that do not meet any of the above criteria.
RECIST immune-related response will be assessed by the criterion below.
- irCR = Disappearance of all target lesions. Lymph nodes <10 mm in short axis.
- irPR = ≥30% decrease in the sum of the LD of target lesions.
- irSD = Failure to meet criteria for irCR or irPR in the absence of irPR. The outcome is reported as the duration of response for each level of level of clinical response.
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2019
- Study start24 Jul 2019
- Primary completion16 Nov 2020
- Study completion20 Jan 2021
Why it stopped: Business decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Merkel Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Susan Pillsbury, Stanford University
- Investigators
- Susan J Knox, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03988647
- Sponsor's protocol ID
- IRB-50888
- Other IDs
- IRB-50888, SKIN0047
- Status last verified
- Aug 2021
- First submitted
- 13 Jun 2019
- Last updated
- 9 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Palliative Radiation Therapy and Anti-PD-1/PD-L1 Checkpoint Blockade in Patients With Metastatic Merkel Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03988647
- Acronym / sponsor ID
- IRB-50888
- Conditions
- Merkel Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business decision
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 24 Jul 2019 (actual)
- Primary completion
- 16 Nov 2020 (actual)
- Study completion
- 20 Jan 2021 (actual)
- First posted
- 17 Jun 2019 (actual)
- Results
- Posted 9 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + Palliative Radiation Therapy | Experimental | Drug: Pembrolizumab, Radiation: Radiation TherapyPembrolizumab 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaPembrolizumab administered at 200 mg IV every 3 weeks | Drug | Pembrolizumab + Palliative Radiation Therapy |
| Radiation Therapy9 Gy X 3 (27 Gy in 3 fractions), or 4-6 Gy X 5 (20-30 Gy in 5 fractions). | Radiation | Pembrolizumab + Palliative Radiation Therapy |
Primary outcome
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.
2 secondary outcomes
Overall Survival (OS)
Time frame: 18 months
Duration of Response (DOR)
Time frame: 15 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Merkel Cell Carcinoma
Active, not recruitingPhase 3
Testing Pembrolizumab Versus Observation in Patients With Merkel Cell Carcinoma After Surgery, STAMP Trial
Pathologic Stage I Cutaneous Merkel Cell Carcinoma AJCC v8, Pathologic Stage II Cutaneous Merkel Cell Carcinoma AJCC v8
RecruitingPhase 1
IFx-Hu2.0 As An Adjunctive Therapy To Pembrolizumab In Advanced Or Metastatic Merkel Cell Carcinoma (MCC)
Advanced Or Metastatic Merkel Cell Carcinoma
Active, not recruitingPhase 1
Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8
RecruitingPhase 1/2
Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8
RecruitingPhase 1/2
A Study to Evaluate ARV-6723 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors
Advanced Solid Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan J Knox, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Radiation Therapy in people with Merkel Cell Carcinoma, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor Response (time frame: 15 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2021.