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

• Sponsor: Vinita Takiar (Other)
• Overall Status: Completed
• CT.gov ID: NCT02759575
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 9
• Location: 1
• Arm: 1
• Actual Duration (Months): 58.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: Pembrolizumab; Radiation: Radiation Therapy; Drug: Cisplatin	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Jan 24, 2019
• Actual Study Completion Date: Feb 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Related Grade 3 or 4 Adverse Events as Assessed by CTCAE V4.0 [30 days following completion of treatment for the first 6 participants]

   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

2. Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma [18 months]

   This is the number of subjects that are laryngectomy-free at 18 months.

Secondary Outcome Measures

1. Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma [12 months]

   This is the number of subjects that are laryngectomy-free at 12 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45219

Sponsors and Collaborators

• Vinita Takiar
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Vinita Takiar, MD, University of Cincinnati

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 1, 2017
• Informed Consent Form - Mar 22, 2018

More Information

Publications

None provided.

• Responsible Party: Vinita Takiar, Assistant Professor of Radiation Oncology, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT02759575
• Other Study ID Numbers: UCCI-HN-15-02
• First Posted: May 3, 2016
• Last Update Posted: Mar 12, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Pembrolizumab

Study Results

Participant Flow

Arm/Group Title	Pembrolizumab
Arm/Group Description	Pembrolizumab every 3 weeks in combination with 7 weeks of radiation therapy and every 3 week cisplatin Pembrolizumab: 200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses Radiation Therapy: 70 Gy in 35 fractions over 7 weeks Cisplatin: 100 mg/m2 every 3 weeks starting on day 1 of chemoradiotherapy. Maximum of 3 doses.
Period Title: Overall Study
STARTED	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Pembrolizumab
Arm/Group Description	Pembrolizumab every 3 weeks in combination with 7 weeks of radiation therapy and every 3 week cisplatin Pembrolizumab: 200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses Radiation Therapy: 70 Gy in 35 fractions over 7 weeks Cisplatin: 100 mg/m2 every 3 weeks starting on day 1 of chemoradiotherapy. Maximum of 3 doses.
Overall Participants	9
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 88.9%
>=65 years	1 11.1%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54
Sex: Female, Male (Count of Participants)
Female	1 11.1%
Male	8 88.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	9 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 11.1%
White	8 88.9%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Related Grade 3 or 4 Adverse Events as Assessed by CTCAE V4.0
Description	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
Time Frame	30 days following completion of treatment for the first 6 participants

Outcome Measure Data

Analysis Population Description

These are the first six participants that completed the study.

Arm/Group Title	Pembrolizumab
Arm/Group Description	Pembrolizumab every 3 weeks in combination with 7 weeks of radiation therapy and every 3 week cisplatin Pembrolizumab: 200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses Radiation Therapy: 70 Gy in 35 fractions over 7 weeks Cisplatin: 100 mg/m2 every 3 weeks starting on day 1 of chemoradiotherapy. Maximum of 3 doses.
Measure Participants	6
Count of Participants [Participants]	2 22.2%

2. Primary Outcome

Title	Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma
Description	This is the number of subjects that are laryngectomy-free at 18 months.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab
Arm/Group Description	Pembrolizumab every 3 weeks in combination with 7 weeks of radiation therapy and every 3 week cisplatin Pembrolizumab: 200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses Radiation Therapy: 70 Gy in 35 fractions over 7 weeks Cisplatin: 100 mg/m2 every 3 weeks starting on day 1 of chemoradiotherapy. Maximum of 3 doses.
Measure Participants	9
Count of Participants [Participants]	9 100%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab
Arm/Group Description	Pembrolizumab every 3 weeks in combination with 7 weeks of radiation therapy and every 3 week cisplatin Pembrolizumab: 200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses Radiation Therapy: 70 Gy in 35 fractions over 7 weeks Cisplatin: 100 mg/m2 every 3 weeks starting on day 1 of chemoradiotherapy. Maximum of 3 doses.
Measure Participants	9
Count of Participants [Participants]	9 100%

Adverse Events

Time Frame	2 years
Arm/Group Title	Pembrolizumab
Arm/Group Description	Pembrolizumab every 3 weeks in combination with 7 weeks of radiation therapy and every 3 week cisplatin Pembrolizumab: 200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses Radiation Therapy: 70 Gy in 35 fractions over 7 weeks Cisplatin: 100 mg/m2 every 3 weeks starting on day 1 of chemoradiotherapy. Maximum of 3 doses.
All Cause Mortality
	Pembrolizumab
	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)
Serious Adverse Events
	Pembrolizumab
	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)
Gastrointestinal disorders
Mucositis oral	1/9 (11.1%)	1
General disorders
Failure to Thrive	1/9 (11.1%)	1
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other- Diabetic Ketoacidosis	1/9 (11.1%)	3
Renal and urinary disorders
Acute Kidney Disease	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Pembrolizumab
	Affected / at Risk (%)	# Events
Total	9/9 (100%)
Blood and lymphatic system disorders
Anemia	3/9 (33.3%)	5
Febrile neutropenia	1/9 (11.1%)	1
Cardiac disorders
Electrocardiogram QT corrected interval prolonged	1/9 (11.1%)	1
Ear and labyrinth disorders
Tinnitus	5/9 (55.6%)	5
Hearing loss	1/9 (11.1%)	1
Ear pain	1/9 (11.1%)	1
Eye disorders
Blurred vision	1/9 (11.1%)	1
Gastrointestinal disorders
Colitis	1/9 (11.1%)	1
Constipation	3/9 (33.3%)	4
Diarrhea	3/9 (33.3%)	3
Dry mouth	8/9 (88.9%)	9
Dysphagia	7/9 (77.8%)	13
Gastroesophageal reflux disease	1/9 (11.1%)	1
Mucositis oral	5/9 (55.6%)	7
Nausea	4/9 (44.4%)	8
Vomiting	3/9 (33.3%)	3
Abdominal pain	1/9 (11.1%)	1
Dyspepsia	1/9 (11.1%)	1
Oral dysesthesia	2/9 (22.2%)	2
Oral pain	1/9 (11.1%)	1
Salivary duct inflammation	5/9 (55.6%)	5
General disorders
Fatigue	8/9 (88.9%)	15
Increased Mucus Production	1/9 (11.1%)	1
Pain	2/9 (22.2%)	3
Localized edema	2/9 (22.2%)	3
Infections and infestations
Orchitis	1/9 (11.1%)	1
Mucosal infection	2/9 (22.2%)	2
Sepsis	1/9 (11.1%)	1
Stoma site infection	2/9 (22.2%)	3
Injury, poisoning and procedural complications
Dermatitis radiation	9/9 (100%)	12
Tenderness (around feeding tube)	1/9 (11.1%)	1
Investigations
Creatinine increased	1/9 (11.1%)	2
Neutrophil count decreased	2/9 (22.2%)	2
Platelet count decreased	1/9 (11.1%)	1
Weight loss	6/9 (66.7%)	14
White blood cell decreased	2/9 (22.2%)	2
Lymphocyte count decreased	2/9 (22.2%)	3
Metabolism and nutrition disorders
Dehydration	3/9 (33.3%)	4
Hypokalemia	4/9 (44.4%)	5
Diabetic Ketoacidosis	1/9 (11.1%)	2
Anorexia	6/9 (66.7%)	10
Hyperglycemia	1/9 (11.1%)	4
Hyperkalemia	1/9 (11.1%)	1
Hypomagnesemia	2/9 (22.2%)	2
Hyponatremia	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/9 (11.1%)	1
Back pain	2/9 (22.2%)	2
Flank pain	1/9 (11.1%)	1
Sensitive fingertips	1/9 (11.1%)	1
Neck soft tissue necrosis	1/9 (11.1%)	1
Pain in extremity	1/9 (11.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Two white spots on ventricular fold	1/9 (11.1%)	1
Tumor pain	1/9 (11.1%)	2
Nervous system disorders
Dysgeusia	8/9 (88.9%)	15
Dizziness	1/9 (11.1%)	1
Headache	1/9 (11.1%)	1
Intermittent lightheadedness	1/9 (11.1%)	1
Paresthesia	1/9 (11.1%)	1
Peripheral sensory neuropathy	1/9 (11.1%)	1
Psychiatric disorders
Anxiety	3/9 (33.3%)	3
Insomnia	2/9 (22.2%)	2
Depression	3/9 (33.3%)	3
Libido decreased	1/9 (11.1%)	1
Renal and urinary disorders
Acute Kidney Injury	4/9 (44.4%)	6
Proteinuria	2/9 (22.2%)	2
Respiratory, thoracic and mediastinal disorders
Cough	4/9 (44.4%)	4
Dyspnea	2/9 (22.2%)	2
Hiccups	2/9 (22.2%)	2
Throat swelling	1/9 (11.1%)	1
Sore Throat	7/9 (77.8%)	12
Voice alteration	2/9 (22.2%)	2
Hoarseness	3/9 (33.3%)	5
Laryngeal edema	3/9 (33.3%)	4
Laryngeal mucositis	1/9 (11.1%)	1
Pharyngeal mucositis	4/9 (44.4%)	4
Productive cough	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/9 (11.1%)	1
Pruritus	2/9 (22.2%)	2
Rash acneiform	1/9 (11.1%)	1
Rash maculo-papular	2/9 (22.2%)	2
Dry skin of lower lip	1/9 (11.1%)	1
Skin ulceration	1/9 (11.1%)	1
Vascular disorders
Lymphedema	3/9 (33.3%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.