Nivolumab and Radiation Therapy or Ipilimumab as Adjuvant Therapy in Treating Patients With Merkel Cell Cancer

NCT03798639 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-18231NCI-2018-03329
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Merkel Cell Carcinoma; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 12 months

Secondary Outcomes (3)

• Recurrence-free survival (RFS) one and half years

  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 from randomization to the date of death, assessed up to 3 years

• Incidence of adverse events (AEs)

  Up to 3 years post treatment

Other Outcomes (1)

• T cell analysis

  Baseline up to 3 years post treatment

Study Arms (2)

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.

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.

Biological: Ipilimumab; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm II (nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm I (nivolumab, radiation therapy); Arm II (nivolumab, ipilimumab)

Radiation Therapy RADIATION

Receive radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, RADIOTHERAPY, RT, Therapy, Radiation

Arm I (nivolumab, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Claire Verschraegen: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Therapeutics; Physical Phenomena

Study Officials

• Claire Verschraegen, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 10, 2019
• Study Start: January 7, 2019
• Primary Completion: December 2, 2022
• Study Completion: December 2, 2022
• Last Updated: April 12, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)