A Study of Chemoradiation Plus Pembrolizumab for Locally Advanced Laryngeal Squamous Cell Carcinoma

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

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Radiation: Radiation Therapy; Drug: Cisplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab; Pembrolizumab every 3 weeks in combination with 7 weeks of radiation therapy and every 3 week cisplatin	Drug: Pembrolizumab; 200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses; Other Names: Keytruda; Radiation: Radiation Therapy; 70 Gy in 35 fractions over 7 weeks; Drug: Cisplatin; 100 mg/m2 every 3 weeks starting on day 1 of chemoradiotherapy. Maximum of 3 doses.; Other Names: Platinol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Grade 3 or 4 Adverse Events as Assessed by CTCAE V4.0	Greater than 2 grade 3 or 4 adverse events that are definitely, probably or possibly related to the pembrolizumab in the first cohort of 6 participants	30 days following completion of treatment for the first 6 participants
Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma	This is the number of subjects that are laryngectomy-free at 18 months.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma	This is the number of subjects that are laryngectomy-free at 12 months.	12 months

Collaborators and Investigators

• Sponsor: Vinita Takiar
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): January 24, 2019
• Study Completion (Actual): February 1, 2021

Study Registration Dates

• First Submitted: April 26, 2016
• First Submitted That Met QC Criteria: April 29, 2016
• First Posted (Estimate): May 3, 2016

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cisplatin; Pembrolizumab
• Other Study ID Numbers: UCCI-HN-15-02