Phase Ib Study of a Monoclonal Antibody to OX40 (MEDI0562) Administered Prior to Surgical Resection in Patients With Head and Neck Squamous Cell Carcinoma or Melanoma
Overview
- Phase
- Phase 1
- Intervention
- MEDI0562
- Conditions
- Head and Neck Cancer
- Sponsor
- Providence Health & Services
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Activation of immune response
- Status
- Active, not recruiting
- Last Updated
- 9 months ago
Overview
Brief Summary
This clinical trial will evaluate the safety and feasibility of a humanized OX40 agonist, MEDI0562, in the pre-operative setting for patients with head and neck squamous cell carcinoma or melanoma.
Detailed Description
This clinical trial is the first to evaluate the safety and feasibility of a humanized OX40 agonist, MEDI0562, in the pre-operative setting for patients with head and neck squamous cell carcinoma or melanoma. Patients will be randomly assigned to one of two MEDI0562 administration schedules; initially 5 patients will enroll to each cohort. All patients will have a tumor biopsy before administration of MEDI0562 and surgery will be performed on approximately day 15 (+/- 2 days). There will be a comparison of a surgical specimen to the original biopsy focusing on the composition and immunologic phenotypes of lymphocyte subsets. Although the primary endpoint of this study is immunological, valuable exploratory data on clinical outcomes will also be obtained. Both the HNSCC and the melanoma patients to be enrolled on this trial are anticipated to have a 50 - 90% probability of recurrence within 5 years after surgery, even with current state-of-the-art post-surgical adjuvant radiation, chemotherapy, or immunotherapy. A recurrence of 25% or less within the 12 months after surgery will be deemed of clinical interest and would inform the design of a larger follow-up study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with advanced head and neck squamous cell carcinoma (HNSCC) or stage IIIb/IIIC melanoma who are candidates for R0 surgical resection
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- •Age 18 years or above
- •Laboratory values:
- •WBC ≥2000/uL
- •Hgb \>8g/dl (patients may be transfused to reach this level)
- •Platelets \>75,000 cells/mm3
- •Serum creatinine 3 X upper limit of laboratory normal
- •Negative bHCG (urine/serum) \[women of childbearing potential only\]
- •AST (SGOT) and ALT (SGPT) \<2.5 X upper limit of laboratory normal
Exclusion Criteria
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca/MedImmune staff and/or staff at the study site)
- •Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- •Receipt of any investigational anticancer therapy during the last 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study treatment
- •Any concurrent chemotherapy, investigational agent, biologic, or hormonal therapy for cancer treatment -- concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- •Local treatment of isolated lesions for palliative intent is acceptable (e.g., local surgery or radiotherapy). -Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. Note: Local treatment of isolated lesions, excluding target lesions, for palliative intent is acceptable. -Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. -History of allogenic organ transplantation.
- •Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent -History of another primary malignancy except for:
- •Malignancy treated with curative intent and with no known active disease ≥1.5 years before the first dose of investigational product and of low potential risk for recurrence
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •Adequately treated carcinoma in situ without evidence of disease -History of leptomeningeal carcinomatosis -Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: patients whose brain metastases have been treated may participate provided they show radiographic stability (imaging at least four weeks apart showing no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either without the use of steroids or are stable on a steroid dose of ≤10mg/day of prednisone or its equivalent and anti-seizure medications for at least 14 days prior to the start of treatment. Patients on a stable dose of seizure medicines for epilepsy unrelated to cancer are eligible for the trial.
- •Active or recent history of diverticulitis. Note: Patients with known diverticulosis are permitted to enroll.
Arms & Interventions
Cohort I
MEDI0562 administration (90mg on day 1) followed by surgical resection (day 15)
Intervention: MEDI0562
Cohort II
MEDI0562 administration (30mg on days 1, 3, 5) followed by surgical resection (day 15)
Intervention: MEDI0562
Outcomes
Primary Outcomes
Activation of immune response
Time Frame: 28 days
The primary objective of this phase Ib clinical trial is to ascertain if there is a difference in immune activation comparing a single dose of MEDI0562 with the equivalent dose divided into a Monday, Wednesday Friday schedule in patients with advanced HNSCC or melanoma. Immune activation will be assessed as a cumulative suppressive index (CSI).
Secondary Outcomes
- Cancer-related clinical outcomes (overall survival)(5 years)
- Cancer-related clinical outcomes (progression free survival)(5 years)
- Surgical complications after MEDI0562(28 days)
- Incidence of Treatment-Emergent Adverse Events in patients with HNSCC or melanoma treated with MEDI0562 (Safety & Tolerability)(5 years)