Merkel Cell CarcinomaPhase 1NCT03798639
Nivolumab and Radiation Therapy or Ipilimumab as Adjuvant Therapy in Treating Patients With Merkel Cell Cancer
A Phase 1 study testing Ipilimumab, Nivolumab and Radiation Therapy in people with Merkel Cell Carcinoma and Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8, run by Claire Verschraegen at 1 site in United States.
Trial summary
This phase I trial studies the side effects and how well nivolumab works when given together with radiation therapy or ipilimumab as adjuvant therapy in treating patients with Merkel cell cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Merkel Cell Carcinoma, Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8, Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8
- What is being tested?
- Ipilimumab, Nivolumab 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
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jan 2019to 2 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Be willing and able to understand and give written informed consent and comply with all study related procedures
- All patients should undergo definitive surgical resection, including when possible sentinel lymph node dissection
- Patients must have recovered after any recent surgery and be ambulatory
- Have node positive disease (stage pIIIA or pIIIB) +/- extracapsular extension
- Have node negative disease and any of the following high risk features
- Tumor size >= 2 cm
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- Margins =< 1-2 cm and re-resection is not possible
- Evidence of perineural or lymphovascular invasion
- Human immunodeficiency virus (HIV) patients with undetectable viral load and CD4+ T-cell counts >= 350 cells/uL
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 16 days of treatment initiation)
- Platelets >= 100,000/mcL in the absence of transfusion support within 7 days of determining eligibility (performed within 16 days of treatment initiation)
- Hemoglobin >= 8 g/dL (performed within 16 days of treatment initiation)
- Serum creatinine =< 1.5 x upper limit of normal (ULN) OR Measured or calculated creatinine clearance >= 40 mL/min creatinine clearance (performed within 16 days of treatment initiation) (Glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl])
- Creatinine clearance should be calculated per institutional standard
- Serum total bilirubin =< 1.5 x ULN OR Except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 x ULN (performed within 16 days of treatment initiation)
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x ULN (performed within 16 days of treatment initiation)
- Female subject of childbearing potential should have a negative urine or serum pregnancy at screening and within 24 hours prior to receiving the first dose of study medication and then every 4 weeks while on treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential should 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 5 months after the last dose of study medication. Subjects should agree to ongoing pregnancy testing during the course of the study and after the end of study therapy. Female subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy. Males must refrain from donating sperm during study participation and for 7 months after the last dose of study medication. Female subject should agree to use an adequate method of contraception starting with the first dose of study therapy through 5 months after the last dose of study therapy
Who cannot join
- Has known distant metastatic MCC
- Has a known history of active TB (Bacillus tuberculosis)
- Hypersensitivity to any study agents
- Have received prior immunotherapy with any PD-1/PDL-1 inhibitors or CTLA-4 antibodies at any time in the past
- Has had prior chemotherapy or radiation therapy for treatment of MCC
- Has a clinically significant medical condition, which in the judgment of the attending physician would contraindicate immunotherapy or radiotherapy, such as serious autoimmune disease, hypersensitivity to investigational product or any component in its formulations, per Food and Drug Administration (FDA) prescription notice
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- Subjects with prior history of non-Merkel cell carcinoma malignancies are excluded except
- Adequately treated basal cell, squamous cell skin cancer, chronic lymphocytic leukemia (CLL) or other indolent malignancies not requiring therapy (ie. active surveillance)
- Adequately treated malignancies and patient has been in complete remission for at least two years
- Patients with history of breast cancer and no evidence of disease on hormonal therapy to prevent recurrence
- Patients with prostate cancer on adjuvant hormonal therapy with undetectable PSA are eligible
- 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 (thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization will be excluded. Inhaled or topical steroids are permitted in the absence of active autoimmune disease
- Has an active infection requiring intravenous systemic therapy
- Solid organ transplant recipients and patients with concurrent hematological malignancies including thymomas, leukemias (other than CLL) and lymphomas actively undergoing treatment or completed < 5 years prior
- Clinically significant cardiovascular disease with uncontrolled arrhythmia, New York Association class 3 or 4 congestive heart failure, history of myocardial infarction within 6 months, or prolonged corrected QT (QTc) > 500 msec
- 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 120 days after the last dose of trial treatment
- Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: Randomized, Multi-Institutional Pilot Study of Nivolumab and Radiation Therapy Versus Nivolumab and Ipilimumab as Adjuvant Therapy for Merkel Cell Carcinoma
This phase I trial studies the side effects and how well nivolumab works when given together with radiation therapy or ipilimumab as adjuvant therapy in treating patients with Merkel cell cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, gamma rays, neutrons, protons or other sources to kill tumor cells and shrink tumors. Giving nivolumab with radiation therapy or ipilimumab after surgery may kill any remaining tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the tolerability of two different experimental immunotherapy regimens in the adjuvant setting in patients with Merkel cell carcinoma (MCC).
SECONDARY OBJECTIVES:
- To assess the safety and tolerability profile of each of the treatment using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
II. To assess the efficacy of each of the treatment arms according to recurrence-free survival (RFS) at one and half years, defined as the time between the date of randomization and the date of first progression (local, regional or distant metastasis) or death (whatever the cause), whichever occurs first.
III. To assess the efficacy of each of the treatment arms according to overall survival (OS) at three years, defined from the time of randomization and the date of death, compared to historical registry control.
EXPLORATORY OBJECTIVES:
- To explore potential biomarkers, next generation T cell receptor (TCR) sequencing will be performed to identify and longitudinally track individual T cell clones thus granting a comprehensive insight into immunological changes that occur within the tumor and peripheral blood throughout the course of the disease.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes at week 0. Treatments repeat every 4 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients also receive radiation therapy on Monday-Friday or 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes at week 0. Treatments repeat every 2 weeks for nivolumab and 6 weeks for ipilimumab for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.
- Conditions
- Merkel Cell Carcinoma, Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8, Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8
- Being tested
- Ipilimumab, Nivolumab, 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.
IpilimumabBiological
Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4
Given IV
NivolumabBiological
Also called BMS-936558, MDX-1106, NIVO, ONO-4538
Given IV
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Irradiate, Irradiated, irradiation
Receive radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Arm I (nivolumab, radiation therapy) | Experimental | Patients receive nivolumab IV over 30 minutes at week 0. Treatments repeat every 4 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients also receive radiation therapy on Monday-Friday or 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Receives: Biological: Nivolumab; Radiation: Radiation Therapy |
| Arm II (nivolumab, ipilimumab) | Active comparator | Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes at week 0. Treatments repeat every 2 weeks for nivolumab and 6 weeks for ipilimumab for up to 1 year in the absence of disease progression or unacceptable toxicity. Receives: Biological: Ipilimumab; Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients completing 12 months of treatment
Will be estimated along with the 95% confidence interval for each arm based on the binomial distribution.
Measured: Up to 12 months
Secondary outcomes (3)
Recurrence-free survival (RFS) one and half years
Kaplan-Meier curves will be generated to summarize the secondary outcomes, RFS and overall survival (OS), for each arm; the differences between groups in terms of hazard ratio for OS/RFS will also be estimated.
Measured: Time between the date of randomization and the date of first progression (local, regional or distant metastasis) or death (whatever the cause), assessed up to one and half years.
Overall survival at three years
Kaplan-Meier curves will be generated to summarize the secondary outcomes, RFS and OS, for each arm; the differences between groups in terms of hazard ratio for OS/RFS will also be estimated.
Measured: Time from randomization to the date of death, assessed up to 3 years
Incidence of adverse events (AEs)
Adverse experiences will be graded and recorded throughout the study and during the follow-up period according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Side effects will be summarized by each treatment group.
Measured: Up to 3 years post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2019
- Study start7 Jan 2019
- Primary completion2 Dec 2022
- Study completion2 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Merkel Cell CarcinomaStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Claire Verschraegen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Claire Verschraegen, Ohio State University Comprehensive Cancer Center
- Investigators
- Claire Verschraegen, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03798639
- Sponsor's protocol ID
- OSU-18231
- Other IDs
- NCI-2018-03329
- Status last verified
- Apr 2024
- First submitted
- 7 Jan 2019
- Last updated
- 12 Apr 2024
- Results posted
- No
- 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 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Multi-Institutional Pilot Study of Nivolumab and Radiation Therapy Versus Nivolumab and Ipilimumab as Adjuvant Therapy for Merkel Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03798639
- Acronym / sponsor ID
- OSU-18231
- Conditions
- Merkel Cell Carcinoma, Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8, Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Claire VerschraegenUniversity, hospital or other
- Study start
- 7 Jan 2019 (actual)
- Primary completion
- 2 Dec 2022 (actual)
- Study completion
- 2 Dec 2022 (actual)
- First posted
- 10 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and how well nivolumab works when given together with radiation therapy or ipilimumab as adjuvant therapy in treating patients with Merkel cell cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, gamma rays, neutrons, protons or other sources to kill tumor cells and shrink tumors. Giving nivolumab with radiation therapy or ipilimumab after surgery may kill any remaining tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- To assess the tolerability of two different experimental immunotherapy regimens in the adjuvant setting in patients with Merkel cell carcinoma (MCC).
SECONDARY OBJECTIVES:
- To assess the safety and tolerability profile of each of the treatment using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
II. To assess the efficacy of each of the treatment arms according to recurrence-free survival (RFS) at one and half years, defined as the time between the date of randomization and the date of first progression (local, regional or distant metastasis) or death (whatever the cause), whichever occurs first.
III. To assess the efficacy of each of the treatment arms according to overall survival (OS) at three years, defined from the time of randomization and the date of death, compared to historical registry control.
EXPLORATORY OBJECTIVES:
- To explore potential biomarkers, next generation T cell receptor (TCR) sequencing will be performed to identify and longitudinally track individual T cell clones thus granting a comprehensive insight into immunological changes that occur within the tumor and peripheral blood throughout the course of the disease.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes at week 0. Treatments repeat every 4 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients also receive radiation therapy on Monday-Friday or 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes at week 0. Treatments repeat every 2 weeks for nivolumab and 6 weeks for ipilimumab for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (nivolumab, radiation therapy) | Experimental | Biological: Nivolumab, Radiation: Radiation TherapyPatients receive nivolumab IV over 30 minutes at week 0. Treatments repeat every 4 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients also receive radiation therapy on Monday-Friday or 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. |
| Arm II (nivolumab, ipilimumab) | Active comparator | Biological: Ipilimumab, Biological: NivolumabPatients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes at week 0. Treatments repeat every 2 weeks for nivolumab and 6 weeks for ipilimumab for up to 1 year in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Be willing and able to understand and give written informed consent and comply with all study related procedures
- All patients should undergo definitive surgical resection, including when possible sentinel lymph node dissection
- Patients must have recovered after any recent surgery and be ambulatory
- Have node positive disease (stage pIIIA or pIIIB) +/- extracapsular extension
- Have node negative disease and any of the following high risk features
Key exclusion criteria (18 listed)
- Has known distant metastatic MCC
- Has a known history of active TB (Bacillus tuberculosis)
- Hypersensitivity to any study agents
- Have received prior immunotherapy with any PD-1/PDL-1 inhibitors or CTLA-4 antibodies at any time in the past
- Has had prior chemotherapy or radiation therapy for treatment of MCC
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 |
|---|---|---|
| IpilimumabAlso: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4Given IV | Biological | Arm II (nivolumab, ipilimumab) |
| NivolumabAlso: BMS-936558, MDX-1106, NIVO, ONO-4538Given IV | Biological | Arm I (nivolumab, radiation therapy), Arm II (nivolumab, ipilimumab) |
| Radiation TherapyAlso: Cancer Radiotherapy, Irradiate, Irradiated, irradiationReceive radiation therapy | Radiation | Arm I (nivolumab, radiation therapy) |
Primary outcome
Percentage of patients completing 12 months of treatment
Time frame: Up to 12 months
Will be estimated along with the 95% confidence interval for each arm based on the binomial distribution.
3 secondary outcomes
Recurrence-free survival (RFS) one and half years
Time frame: Time between the date of randomization and the date of first progression (local, regional or distant metastasis) or death (whatever the cause), assessed up to one and half years.
Overall survival at three years
Time frame: Time from randomization to the date of death, assessed up to 3 years
Incidence of adverse events (AEs)
Time frame: Up to 3 years post treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2024.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Claire Verschraegen, MD principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ipilimumab, Nivolumab and Radiation Therapy in people with Merkel Cell Carcinoma and Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8, run by Claire Verschraegen 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 20 inclusion and 18 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: finished, as of the sponsor's last update on 12 Apr 2024. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of patients completing 12 months of treatment (time frame: Up to 12 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 12 Apr 2024.