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

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02759575
• Other study ID #: UCCI-HN-15-02
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2016
• Est. completion date: February 2021

Study information

• Verified date: March 2021
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: February 2021
• Est. primary completion date: January 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer

Intervention

Drug:
• Pembrolizumab
200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses

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.

Locations

Country	Name	City	State
United States	University of Cincinnati Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Vinita Takiar	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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