Clinical trial NCT02759575: A Study of Chemoradiation Plus Pembrolizumab for Locally Advanced Laryngeal Squamous Cell Carcinoma
Official title: A Phase I/II Study of Chemo Radiation Plus the Anti-Programmed Death-1 (Anti-PD-1) Antibody, Pembrolizumab (MK-3475) for Locally Advanced Laryngeal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Head and Neck Cancer
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-05-03
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to test the safety and the benefit of adding pembrolizumab (a therapy that activates the immune system to fight cancer) to standard of care treatment for larynx cancer. The standard of care treatment will include chemotherapy and radiation for 7 weeks.

Detailed description: This study is an open label, single arm study which will enroll patients with locally advanced squamous cell carcinomas of the larynx. Positive tumor PDL1 expression by IHC will not be required for enrollment.

All patients with receive Pembrolizumab and cisplatin in combination with radiation. Pembrolizumab 200 mg flat dose given Q21 days will begin 3 weeks prior to initiation of chemoradiation and continued through the 21-day cycle until completion of chemoradiation. Cisplatin will be given 100 mg/m2 every 21 days during radiation as per standard of care.

Pembrolizumab has well defined toxicities as single agent and has non-overlapping mechanisms of action with cisplatin and radiation. The safety of these agents used in combination has not been previously described, therefore the study will begin with a safety run-in phase 1 followed by the phase II design. See statistical section for details.

Eligibility criteria: Inclusion Criteria:

* Biopsy-proven, previously untreated stage III or IV squamous cell carcinoma of the larynx, Primary tumor stage (T2, T3) and nodal stage (N0, N1, N2, N3).
* Measurable disease based on RECIST 1.1.
* Performance status 0 or 1 on Eastern Cooperative Oncology Group Performance Scale.
* Anticipated survival minimum of 12 months.
* Adequate labs

Exclusion Criteria:

* Patients with T1 primary tumor or T4 large volume tumor that has resulted in larynx dysfunction at baseline (for example tumor largely penetrating into base of tongue and resulting in inability to swallow at baseline)
* Prior radiation therapy to the larynx area or involved neck.
* Distant metastasis
* Known history of active tuberculosis (TB), autoimmune disease, pneumonitis, infection, HIV, Hepatitis B, or Hepatitis C

Primary outcomes:
measure: Number of Participants With Treatment-Related Grade 3 or 4 Adverse Events as Assessed by CTCAE V4.0
timeFrame: 30 days following completion of treatment for the first 6 participants
measure: Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma
timeFrame: 18 months
Secondary outcomes:
measure: Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma
timeFrame: 12 months
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Vinita Takiar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Frankart AJ, Sadraei NH, Huth B, Redmond KP, Barrett WL, Kurtzweil N, Riaz MK, Wise-Draper T, Rodriguez CP, Adelstein DJ, Takiar V. A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer. Laryngoscope Investig Otolaryngol. 2022 Mar 17;7(2):437-443. doi: 10.1002/lio2.780. eCollection 2022 Apr.