Study of Cemiplimab - TP Induction Chemotherapy in Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck

NCT05376553 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 1 other identifier: STUDY-21-01683
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the safety and tolerability of two dosing schedules of cemiplimab given in combination with cisplatin and docetaxel induction chemotherapy (TPI) in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Cemiplimab is FDA approved for treatment of basal cell and squamous cell carcinoma of the skin as well as non-small cell lung cancer but not for squamous cell carcinoma of head and neck.

Conditions

Locally Advanced Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  The dose-limiting toxicity (DLT) will be the basis for safety and toxicity of Cemiplimab -TP that will be measured and reported only during the first cycle of Cemiplimab -TP for the first 6 study objects in each cohort A and B since the majority of the DLT occurs after the first treatment cycle in multiple phase I oncology clinical trials. DLTs must be related to a study drug, cemiplimab. Known and expected chemotherapy (TP, standard of care) adverse events not related to cemiplimab will not be defined as DLTs.

  During first cycle of cemiplimab (day 14)

• Dose-limiting toxicity (DLT)

  The dose-limiting toxicity (DLT) will be the basis for safety and toxicity of Cemiplimab -TP that will be measured and reported only during the first cycle of Cemiplimab -TP for the first 6 study objects in each cohort A and B since the majority of the DLT occurs after the first treatment cycle in multiple phase I oncology clinical trials. DLTs must be related to a study drug, cemiplimab. Known and expected chemotherapy (TP, standard of care) adverse events not related to cemiplimab will not be defined as DLTs.

  After 3 weeks of cemiplimab

Secondary Outcomes (20)

• Adverse events during induction therapy

  At the end of Cycle 3 (each cycle is 21 days)

• Blood Pressure

  At the end of Cycle 3 (each cycle is 21 days)

• Heart Rate

  At the end of Cycle 3 (each cycle is 21 days)

• Temperature

  At the end of Cycle 3 (each cycle is 21 days)

• Complete White Count (CBC)

  At the end of Cycle 3 (each cycle is 21 days)

Study Arms (2)

Cohort A

EXPERIMENTAL

* 3 cycles of Cemiplimab-TP induction chemotherapy will be delivered in cohort A. * Cemiplimab-TP chemotherapy will be given every 21 days starting on days 1, 22 and 43, etc. (+ 2 days) with TP given on days 1, 22, and 43 (+/- 2 days) and Cemiplimab given on days 14, 35, 56 (+/- 2 days). * Patients in cohort A will get 3 doses of Cemiplimab during induction therapy.

Drug: Cemiplimab; Drug: Cisplatin; Drug: Docetaxel

Cohort B

EXPERIMENTAL

* In cohort B first dose of Cemiplimab will be given 7 days prior to TP followed by TP given on days 1,22,43 (+/- 2 days) and Cemiplimab given on days 14, 35, 56 (+/- 2 days). * Patient in cohort B will get 4 doses of Cemiplimab during induction therapy.

Drug: Cemiplimab; Drug: Cisplatin; Drug: Docetaxel

Interventions

Cemiplimab DRUG

350mg intravenous infusion over 30 minutes

Cohort A; Cohort B

Cisplatin DRUG

100mg/m² intravenous infusion over 60 minutes to 3 hours, mixed in 1000 ml of normal saline Schedule: Day 1, every 21 days (+ 2 days)

Cohort A; Cohort B

Docetaxel DRUG

75 mg/2 intravenous infusion over 60 minutes, mixed as described in Schedule: Day 1, every 21days (+ 2 days)

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with stage III or IV, previously untreated, non-metastatic, locally advanced HNSCC (patients may have had previous surgery, but not chemotherapy or radiotherapy).
• a) Patients with oral cancer, HPV negative oropharyngeal cancer, high risk HPV+ oropharyngeal HNSCC confirmed by PCR. Patients with unknown primary, supraglottic, nasopharyngeal, and hypopharyngeal SCC will be allowed. High risk HPV defined as one of the following: HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82.
• A pretreatment biopsy of the primary site sufficient for immune studies is required.
• Age \>/= 18 years
• ECOG PS 0-1
• Hemoglobin \> 8.0 g/dl, absolute neutrophil count \> 1,500/mm3, platelet count \> 100,000/mm3
• Predicted life expectancy \>/= 12 weeks
• Total bilirubin \<2.5 x Upper limit of normal (ULN); AST (SGOT) \< 2.5 x ULN; ALT (SGPT) \< 2.5 x ULN; serum creatinine \</= 1.5 x ULN (Gilbert's disease allowed with elevated bilirubin)
• Patients must be accessible for repeat dosing and follow-up
• Patients - both males and females - with reproductive potential must agree to practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test at baseline and on Day 1
• Patients must provide verbal and written informed consent to participate in the study.
• A biopsy of the primary tumor or lymph node must be available for testing and immune evaluation

You may not qualify if:

• Locally advanced EBV positive nasopharyngeal cancer, malignancies other than SCC head and neck cancer except surgically treated malignancies that are not active (e.g. surgically treated thyroid cancer, prostate cancer, breast cancer etc.) for 3 years or more and no evidence of active recurrence.
• History of pneumonitis
• History of prior immunotherapy
• History of receiving PI3K inhibitors.
• Patients at 1.5mg or more a day of dexamethasone (or equivalent).
• History of significant cardiac disease unless the disease is well-controlled
• Grade 2 peripheral neuropathy
• No excessive alcohol consumption will be allowed
• Serious comorbid illness, and involuntary weight loss of more than 20% of body weight in the 3 months preceding study entry
• History of cerebrovascular accident (CVA) within 12 months prior to registration or that is not stable
• History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent.
• Pregnant or breast-feeding females.
• GI abnormalities including inability to take oral medication, requirement for IV alimentation, active peptic ulcer, or prior surgical procedures affecting absorption
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug
• Any type of active seizure disorder

Sponsors & Collaborators

• Krzysztof Misiukiewicz: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Interventions

cemiplimab; Cisplatin; Docetaxel

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Krzysztof Misiukiewicz, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 17, 2022
• Study Start: July 20, 2022
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: November 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose. To achieve aims in the approved proposal. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.

Locations

US (1)