Ipilimumab, Cetuximab, and Intensity-Modulated Radiation Therapy in Treating Patients With Previously Untreated Stage III-IVB Head and Neck Cancer
A Phase Ib Trial of Concurrent Cetuximab (ERBITUX®) and Intensity Modulated Radiotherapy (IMRT) With Ipilimumab (YERVOY®) in Locally Advanced Head and Neck Cancer
7 other identifiers
interventional
19
1 country
1
Brief Summary
This phase Ib trial studies the side effects and best dose of ipilimumab when given together with cetuximab and intensity-modulated radiation therapy (IMRT) in treating patients with previously untreated stage III-IVB head and neck cancer. Monoclonal antibodies, such as ipilimumab and cetuximab, may block tumor growth in different ways by targeting certain cells. Specialized radiation therapy, such as IMRT, that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving ipilimumab together with cetuximab and IMRT may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Apr 2013
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 9, 2013
CompletedFirst Submitted
Initial submission to the registry
September 3, 2013
CompletedFirst Posted
Study publicly available on registry
September 5, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 29, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
July 6, 2018
CompletedJune 15, 2023
June 1, 2023
3.6 years
September 3, 2013
June 14, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Proportion of dose limiting toxicities at each dose level assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Up to 12 weeks
Secondary Outcomes (7)
Clinical response by Response Evaluation Criteria in Solid Tumors criteria
Up to 5 years
Progression free survival
Up to 5 years
T cell phenotypes
Up to 5 years
T regulatory cell counts
Up to 5 years
Myeloid-derived suppressor cell (MDSC) cell counts
Up to 5 years
- +2 more secondary outcomes
Study Arms (1)
Treatment (cetuximab, IMRT, and ipilimumab)
EXPERIMENTALPatients receive cetuximab IV over 60-120 minutes on days 1, 8, 15, and 22. Treatment with cetuximab repeats every 4 weeks for 2 courses. Beginning in week 2 of course 1, patients undergo concurrent IMRT 5 days per week for 7 weeks. Beginning in week 4 (day 1 of course 2) patients also receive ipilimumab IV over 90 minutes once every 21 days for 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may undergo surgery after completion of therapy.
Interventions
Given IV
Undergo IMRT
Given IV
Eligibility Criteria
You may qualify if:
- American Joint Committee on Cancer (AJCC) stage III/IVB, excluding T1N1, histologically or cytologically confirmed squamous cell carcinoma or undifferentiated carcinoma of the head and neck; patients should not have distant metastasis; primary sites include: oropharynx, hypopharynx, larynx
- Patients must have high or intermediate risk disease, defined as follows:
- High risk: non-oropharyngeal subsite including larynx or hypopharynx (p16 status not required) or human papilloma virus (HPV)/p16- oropharynx subsite
- Intermediate risk: HPV/p16+ oropharyngeal squamous cell cancer with: \>= 10 pack (pk)-year (yr) smoking history and \>= N2 nodal disease, or the presence of T4 tumor or N3 nodal disease, irrespective of smoking status
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- Patients should be newly diagnosed HNSCC, with no prior therapy for this disease
- Eastern Cooperative Oncology Group (ECOG) performance status typically =\< 1 (Karnofsky \>= 70%)
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,200/mcL
- Platelets \>= 75,000/mcL
- Total bilirubin =\< 2 mg/dL (=\< 3 mg/dL in case of Gilbert's syndrome)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2 times institutional upper limit of normal (IULN)
- Creatinine clearance \>= 40 mL/min/1.73 m\^2
- Patients must have the ability to understand and to sign written informed consent
You may not qualify if:
- Patients who have had prior chemotherapy, radiotherapy, or surgery with curative intent for HNSCC
- Patients with a history of prior treatment with ipilimumab, anti-programmed cell death 1 (PD 1) antibody, cluster of differentiation 137 (CD137) agonist or other immune activating therapy such as anti-cluster of differentiation 40 (CD 40) antibody
- Patients who are receiving any other investigational agents
- Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic non-gastrointestinal autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis)
- Patients with known immunodeficiency disorder, or presumed to be unable to respond to anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) monoclonal antibody (mAb)
- Patients with distant metastatic disease (stage IVC)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab or ipilimumab
- Patient is \< 2 years free from a second primary malignancy unless the other malignancy is non-melanomatous skin cancer or an in-situ tumor treated with curative intent
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; patients with chronic hepatitis B or hepatitis C infections are excluded
- Pregnant women are excluded from this study
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Related Publications (1)
Ferris RL, Moskovitz J, Kunning S, Ruffin AT, Reeder C, Ohr J, Gooding WE, Kim S, Karlovits BJ, Vignali DAA, Duvvuri U, Johnson JT, Petro D, Heron DE, Clump DA, Bruno TC, Bauman JE. Phase I Trial of Cetuximab, Radiotherapy, and Ipilimumab in Locally Advanced Head and Neck Cancer. Clin Cancer Res. 2022 Apr 1;28(7):1335-1344. doi: 10.1158/1078-0432.CCR-21-0426.
PMID: 35091445DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robert L Ferris
University of Pittsburgh Cancer Institute (UPCI)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 3, 2013
First Posted
September 5, 2013
Study Start
April 9, 2013
Primary Completion
October 29, 2016
Study Completion
July 6, 2018
Last Updated
June 15, 2023
Record last verified: 2023-06