A Phase Ib Trial of Concurrent Cetuximab (ERBITUX®) and Intensity Modulated Radiotherapy (IMRT) With Ipilimumab (YERVOY®) in Locally Advanced Head and Neck Cancer

Cancer of Head and Neck Clinical Trial

Official title:

A Phase Ib Trial of Concurrent Cetuximab (ERBITUX®) and Intensity Modulated Radiotherapy (IMRT) With Ipilimumab (YERVOY®) in Locally Advanced Head and Neck Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01860430
• Other study ID #: 12-084
• Secondary ID: 9196
• Status: Active, not recruiting
• Phase: Phase 1
• First received: April 29, 2013
• Last updated: March 28, 2018
• Start date: April 2013
• Est. completion date: March 2018

Study information

• Verified date: March 2018
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial is aimed to establish a recommended starting dose of ipilimumab for a future efficacy trial when used in combination with intensity modulated radiation therapy (IMRT) and cetuximab.

Description:

The investigators proposed to integrate anti-CTLA-4 specific mAb, ipilimumab, into a standard regimen of cetuximab plus RT (70-74.0 Gy) in a dose finding, phase I trial, to inform the design of a future phase II clinical trial which would determine clinical efficacy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: March 2018
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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: p16- Intermediate risk: p16+, = 10 pack-year tobacco exposure and = N2 disease.

• 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 CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease.

• Patients should be newly diagnosed HNSCC, with no prior therapy for this disease.

• Age >18 years.

• ECOG performance status typically <1 (Karnofsky >70%)

• Patients must have acceptable organ and marrow function as defined below:

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) AST/ALT = 2 times institutional ULN creatinine clearance >40 mL/min/1.73 m2

• 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-PD 1 antibody, CD137 agonist or other immune activating therapy such as anti-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]); 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-CTLA4 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 because of potential effects on immune function and/ or drug interactions, as well as the potential for confounded interpretation of immune-related adverse events such as hepatic inflammation occurring on protocol.

• Pregnant women are excluded from this study because ipilimumab may have the potential for teratogenic or abortifacient effects. These potential risks may also apply to other agents used in this study.

• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ipilimumab and immunosuppressed individuals. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Related Conditions & MeSH terms

• Cancer of Head and Neck
• Head and Neck Neoplasms

Intervention

Drug:
• Cetuximab/IMRT Plus Ipilimumab
Cetuximab/IMRT Plus Ipilimumab (14 Week Regimen) IMRT, Weeks 2-8: 70-74.0 Gy with 2.0 Gy daily fractions delivered in 7-7.5 weeks Cetuximab, Weeks 1-8 Week 1: 400 mg/m2 Weeks 2-8 (concurrent with IMRT): 250 mg/m2/week Ipilimumab, Weeks 5, 8, 11, 14 Ipilimumab dose will be determined by cohort (1, 3, 6, or 10 mg/kg)

Locations

Country	Name	City	State
United States	UPMC CancerCetner	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Robert Ferris	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ipilimumab dose	To identify the starting dose of ipilimumab, in combination with standard cetuximab-IMRT in patients with high- or intermediate-risk, locally advanced HNSCC, for use in a future clinical efficacy trial.	2 years
Secondary	clinical response	To estimate the clinical response of patients with high- or intermediate-risk, locally-advanced HNSCC treated with above regimen using RECIST 1.1 criteria.	2 years
Secondary	progression-free survival	To estimate the 2-year progression-free survival of patients with high- or intermediate-risk, locally-advanced HNSCC treated with the above regimen.	2 years
Secondary	tissue biomarkers	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.	2 years
Secondary	dose-response modeling	To estimate the association by dose-response modeling between dose of Ipilimumab, clinical response and biomarkers.	2 years