Clinical trial NCT02274155: Anti-OX40 Antibody in Head and Neck Cancer Patients
Official title: Phase Ib Study of a Monoclonal Antibody to OX40 (MEDI6469) Administered Prior to Definitive Surgical Resection Patients With Locoregionally Advanced, Oral Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Cancer
Keywords: Head and Neck Cancer
anti-OX40 antibody
MEDI6469
Immunotherapy
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
Collaborators: name: MedImmune LLC
First posted: 2014-10-24
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the safety of the anti-OX40 antibody, MEDI6469, given prior to surgery in patients with advanced head and neck squamous cell carcinoma.

Detailed description: This phase Ib clinical trial uses MEDI6469 at various dose intervals prior to definitive surgical resection of patients with stage III and IV Oral Head and Neck Squamous Cell Carcinoma (OHNSCC) with the primary objective of determining the safety and feasibility of preoperative MEDI6469 administration. In addition, tumor tissue and peripheral blood will be obtained for exploratory immunologic end points including measurements of tumor infiltrating immune cell populations based on flow cytometry and immunohistochemistry as well as circulating immunological parameters that may correlate with changes induced by MEDI6469 administration.

Eligibility criteria: Inclusion Criteria:

* Patients with treatment naive, resectable, stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx who are candidates for definitive surgical resection followed by standard risk adapted adjuvant therapy.
* Histologic or cytologic diagnosis of a primary OHNSCC with no radiological evidence of metastatic disease is acceptable. Patients with bone or cartilage invasion and any T or N stage are acceptable.
* Patients with oral cavity primaries will be managed using conventional transoral or transcervical techniques; oropharynx or hypopharynx tumor will be managed with transoral robotic surgery; and larynx tumors (T3/T4 with thyroid cartilage invasion) will be managed by either total laryngectomy or larynx preservation surgery.
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Laboratory values (performed within 28 days prior to enrollment) within protocol defined range
* Ability to give informed consent and comply with the protocol. Patients with a history of psychiatric illness must be judged able to understand the investigational nature of the study and the risks associated with the therapy.
* No active gastrointestinal bleeding.
* Anticipated lifespan greater than 12 weeks.

Exclusion Criteria:

* Locoregionally unresectable or Metastatic disease (stage IVB)
* Active infection.
* Active autoimmune disease including patients with Inflammatory Bowel Disease as determined by an autoimmune questionnaire.
* Previous treatment with mouse monoclonal antibodies
* Need for chronic maintenance oral steroids \> 5mg prednisone daily equivalent.
* Any medical or psychiatric condition that in the opinion of the investigator would preclude compliance with study procedures.

Primary outcomes:
measure: Safety and feasibility of definitive surgical resection for locoregionally advanced OHNSCC following MEDI6469 administration
timeFrame: 55 Days
Secondary outcomes:
measure: Immunologic phenotypes of lymphocyte subsets
timeFrame: 55 days
Other outcomes:
measure: Clinical Outcome of Imaging
timeFrame: 5 years
Locations:
city: Portland
country: United States
facility: Portland Providence Medical Center
state: Oregon
Study officials:
affiliation: Providence Cancer Center
name: Richard B. Bell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Duhen R, Ballesteros-Merino C, Frye AK, Tran E, Rajamanickam V, Chang SC, Koguchi Y, Bifulco CB, Bernard B, Leidner RS, Curti BD, Fox BA, Urba WJ, Bell RB, Weinberg AD. Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. Nat Commun. 2021 Feb 16;12(1):1047. doi: 10.1038/s41467-021-21383-1.