- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01935921
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
Study Overview
Status
Conditions
- Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7
- Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7
- Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7
- Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7
- Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7
- Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7
- Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7
- Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7
- Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7
Detailed Description
PRIMARY OBJECTIVES:
I. To identify the starting dose of ipilimumab, in combination with standard cetuximab-IMRT in patients with high- or intermediate-risk, locally advanced head and neck squamous cell carcinoma (HNSCC), for use in a future clinical efficacy trial.
SECONDARY OBJECTIVES:
I. To estimate the clinical response of patients with high- or intermediate-risk, locally advanced HNSCC treated with above regimen using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
II. To estimate the 2-year progression-free survival of patients with high- or intermediate-risk, locally advanced HNSCC treated with the above regimen.
III. To investigate serum, lymphocyte and tissue biomarkers as predictors of progression-free survival, toxicity and other outcome parameters in patients with high- or intermediate-risk, locally advanced HNSCC treated with above regimen.
IV. To estimate the association by dose-response modeling between dose of ipilimumab, clinical response and biomarkers.
OUTLINE: This is a dose-escalation study of ipilimumab.
Patients receive cetuximab intravenously (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.
After completion of study treatment, patients are followed up every 12 weeks for 1 year, every 6 months for 1 year, and then every 12 months for 3 years.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15232
- University of Pittsburgh Cancer Institute (UPCI)
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (cetuximab, IMRT, and ipilimumab)
Patients 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.
|
Correlative studies
Given IV
Other Names:
Undergo IMRT
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Proportion of dose limiting toxicities at each dose level assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame: Up to 12 weeks
|
Up to 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical response by Response Evaluation Criteria in Solid Tumors criteria
Time Frame: Up to 5 years
|
Will be analyzed by generalized linear models with dose-response analysis using logistic regression.
|
Up to 5 years
|
Progression free survival
Time Frame: Up to 5 years
|
Will be analyzed by generalized linear models.
|
Up to 5 years
|
T cell phenotypes
Time Frame: Up to 5 years
|
Up to 5 years
|
|
T regulatory cell counts
Time Frame: Up to 5 years
|
Up to 5 years
|
|
Myeloid-derived suppressor cell (MDSC) cell counts
Time Frame: Up to 5 years
|
Up to 5 years
|
|
HPV status
Time Frame: Up to 5 years
|
Up to 5 years
|
|
Serum factors and tumor infiltrates
Time Frame: Up to 5 years
|
Up to 5 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Robert L Ferris, University of Pittsburgh Cancer Institute (UPCI)
Publications and helpful links
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 (Estimated)
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
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Neoplasms, Squamous Cell
- Head and Neck Neoplasms
- Carcinoma
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunologic Factors
- Immune Checkpoint Inhibitors
- Antibodies
- Immunoglobulins
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Ipilimumab
- Cetuximab
Other Study ID Numbers
- NCI-2013-00807 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA047904 (U.S. NIH Grant/Contract)
- 9196 (CTEP)
- 12-084
- UPCI 12-084
- NCI 9196
- P50CA097190 (U.S. NIH Grant/Contract)
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 Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7
-
National Cancer Institute (NCI)Active, not recruitingStage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7 | Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 | Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IVB Laryngeal Squamous Cell Carcinoma AJCC... and other conditionsUnited States, Canada
-
National Cancer Institute (NCI)NRG OncologyCompletedStage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7 | Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 | Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IVB Laryngeal Squamous Cell Carcinoma AJCC... and other conditionsUnited States
-
Emory UniversityNational Cancer Institute (NCI); National Institutes of Health (NIH); ExelixisActive, not recruitingRecurrent Head and Neck Squamous Cell Carcinoma | Recurrent Hypopharyngeal Squamous Cell Carcinoma | Recurrent Laryngeal Squamous Cell Carcinoma | Recurrent Oral Cavity Squamous Cell Carcinoma | Recurrent Oropharyngeal Squamous Cell Carcinoma | Stage IV Hypopharyngeal Squamous Cell Carcinoma... and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingHead and Neck Squamous Cell Carcinoma | Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IV Laryngeal Squamous Cell Carcinoma AJCC v7 | Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 | Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IVA Oral Cavity... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedMetastatic Squamous Cell Carcinoma of the Hypopharynx | Metastatic Squamous Cell Carcinoma of the Larynx | Metastatic Squamous Cell Carcinoma of the Oral Cavity | Metastatic Squamous Cell Carcinoma of the Oropharynx | Recurrent Hypopharyngeal Squamous Cell Carcinoma | Recurrent Laryngeal Squamous... and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingRecurrent Hypopharyngeal Squamous Cell Carcinoma | Recurrent Laryngeal Squamous Cell Carcinoma | Recurrent Oropharyngeal Squamous Cell Carcinoma | Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7 | Stage IVA Oropharyngeal Squamous... and other conditionsUnited States, Puerto Rico, South Africa
-
National Cancer Institute (NCI)NRG OncologyRecruitingStage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IV Laryngeal Squamous Cell Carcinoma AJCC v7 | Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 | Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7 | Oropharyngeal p16INK4a-Negative Squamous Cell Carcinoma | Stage... and other conditionsUnited States, Canada, China
-
National Cancer Institute (NCI)CompletedRecurrent Colon Carcinoma | Recurrent Rectal Carcinoma | Recurrent Hypopharyngeal Squamous Cell Carcinoma | Recurrent Laryngeal Squamous Cell Carcinoma | Recurrent Oropharyngeal Squamous Cell Carcinoma | Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IVA Laryngeal Squamous Cell... and other conditionsUnited States
-
National Cancer Institute (NCI)TerminatedStage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 | Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7 | Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 | Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7 | Stage III Oral Cavity Squamous Cell Carcinoma... and other conditionsUnited States
-
University of ArizonaNational Cancer Institute (NCI)TerminatedHPV Positive Oropharyngeal Squamous Cell Carcinoma | Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7 | Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7 | CDKN2A-p16 Positive | Stage I Oropharyngeal Squamous Cell Carcinoma AJCC V7 | Stage II Oropharyngeal Squamous Cell Carcinoma...United States
Clinical Trials on Laboratory Biomarker Analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States