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

Official title

Phase 1 Study of Cemiplimab - TP Induction Chemotherapy in Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Overview

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.

Interventions

• Drug Cemiplimab
  350mg intravenous infusion over 30 minutes
• Drug Cisplatin
  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)
• Drug Docetaxel
  75 mg/2 intravenous infusion over 60 minutes, mixed as described in Schedule: Day 1, every 21days (+ 2 days)

Primary outcome measures

• Dose-limiting toxicity (DLT) [Time frame: During first cycle of cemiplimab (day 14)]
• Dose-limiting toxicity (DLT) [Time frame: After 3 weeks of cemiplimab]

Secondary outcome measures (12)

• Adverse events during induction therapy [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Blood Pressure [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Heart Rate [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Temperature [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Complete White Count (CBC) [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Sodium [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Potassium [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Magnesium [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Bicarbonate (CO2) [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Phosphate [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Calcium [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Blood Urea Nitrogen (BUN) [Time frame: At the end of Cycle 3 (each cycle is 21 days)]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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
• Patients with history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
• Use of strong or moderate CYP3A4 or CYP1A2 inhibitors/inducers, with the exception of low- dose steroids, within 14 days prior to Day 1 dosing
• Symptomatic brain metastases that are not stable, require steroids, or that have required radiation within the last 28 days
• Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study
• History of Hepatitis c or HIV infection, autoimmune disease (except vitiligo and Hashimoto's thyroiditis), or major organ transplant
• Any irradiation or chemotherapy in the past and no major surgical procedure in the last 4 weeks
• Any other concomitant anticancer therapies
• Patients will be excluded if they received any prior chemotherapy, radiotherapy, or treatment with biologic response modifiers (except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix)
• History of colitis or chronic diarrheal illness
• History of, or active, co-morbid medical condition, which in the opinion of the investigator, would raise significant risk to the patient.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Icahn School of Medicine at Mount Sinai — New York

Identifiers

NCT: NCT05376553 · STUDY-21-01683

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗