Clinical trial NCT02262741: A Phase I Study to Evaluate the Safety, Tolerability and Efficacy of MEDI4736 (Durvalumab) With Tremelimumab in Head and Neck Cancer
Official title: A Phase I Study to Evaluate the Safety, Tolerability, and Efficacy of MEDI4736 in Combination With Tremelimumab in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Squamous Cell Carcinoma of the Head and Neck
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2014-10-13
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of MEDI4736 in combination with tremelimumab in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck.


Eligibility criteria: Inclusion Criteria:

1. Male and female subjects
2. 18 years and older
3. Histologically or cytologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx or larynx) that is incurable by local therapy.
4. Subjects who are treatment-naive or pretreated (prior anti-PD-1 or anti-PD-L1 required) in the recurrent/metastatic setting.
5. Subject eligibility will be based on PD-L1 expression as determined by a specified IHC assay.

Exclusion Criteria:

1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment, receipt of last dose of an approved anticancer therapy within 21 days
2. Concurrent or prior use of immunosuppressive medication within 14 days
3. Active or prior documented autoimmune or inflammatory disease within 3 years with some exceptions.

Primary outcomes:
measure: Number of subjects reporting adverse events
timeFrame: Screening through 3 months after the last dose of study medication
measure: Number of subjects reporting serious adverse events
timeFrame: Screening through 3 months after the last dose of study medication
measure: Number of subjects experiencing dose-limiting toxicities
timeFrame: First dose of study medications through 4 weeks after the first dose of study medication
measure: Change from Baseline in laboratory evaluations
timeFrame: Screening through 3 months after the last dose of study medication
measure: Change from Baseline in electrocardiograms
timeFrame: Screening through 3 months through last dose of study medication
measure: Change from Baseline in vital signs
timeFrame: Screening through 3 months after the last dose of study medication
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Screening through 5 years after the last subject receives the first dose of study medication
measure: Individual MEDI4736 concentrations
timeFrame: First dose of MEDI4736 through 3 months after the last dose of study medication
measure: Number of subjects that develop changes in detectable antidrug antibodies to MEDI4736
timeFrame: First dose of MEDI4736 through 6 months after the last dose of study medication
measure: Disease Control Rate
timeFrame: Screening through 5 years after the last subject receives the first dose of study medication
measure: Duration of Response
timeFrame: Screening through 5 years after the last subject receives the first dose of study medication
measure: Progression Free Survival
timeFrame: Screening through 5 years after the last subject receives the first dose of study medication
measure: Overall Survival
timeFrame: Screening through 5 years after the last subject receives the first dose of study medication
measure: Individual tremelimumab concentrations
timeFrame: First dose of tremelimumab through 3 months after the last dose of study medication
measure: MEDI4736 area under the concentration-curve
timeFrame: First dose of MEDI4736 through 3 months after the last dose of study medication
measure: Tremelimumab area under the concentration-curve
timeFrame: First dose of tremelimumb through 3 months after the last dose of study medication
measure: Number of subjects that develop changes in detectable antidrug antibodies to tremelimumab
timeFrame: First dose of tremelimumab through 6 months after the last dose of study medication
Other outcomes:
measure: Changes in Biomarkers
timeFrame: Screening through 3 months after the last patient receives the first dose of study medication
measure: Change from Baseline in Patient-Reported Outcomes
timeFrame: Screening through 5 years after the last patient receives the first dose of study medication
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: La Jolla
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Fairway
country: United States
facility: Research Site
state: Kansas
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: London
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References: