Clinical Trials /

A Window of Opportunity Study of KTN3379 in Surgically Resectable Head and Neck Cancer Patients

NCT02473731

Description:

The purpose of this study is to evaluate the activity and safety of KTN3379 in head and neck cancer patients and to explore downstream molecular pathways to identify tumor response and resistance mechanisms by evaluating various biomarkers before and after treatment.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Window of Opportunity Study of KTN3379 in Surgically Resectable Head and Neck Cancer Patients
  • Official Title: A Window of Opportunity Study of KTN3379 in Surgically Resectable Head and Neck Cancer Patients

Clinical Trial IDs

  • ORG STUDY ID: KTN3379-CL-002
  • NCT ID: NCT02473731

Conditions

  • Squamous Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
KTN3379A

Purpose

The purpose of this study is to evaluate the activity and safety of KTN3379 in head and neck cancer patients and to explore downstream molecular pathways to identify tumor response and resistance mechanisms by evaluating various biomarkers before and after treatment.

Detailed Description

      This is an open-label study in patients with squamous cell carcinoma of the head and neck
      (SCCHN) scheduled for surgery. Two cohorts of SCCHN patients, HPV negative and HPV positive,
      will be treated with KTN3379 to evaluate effects on ErbB3 phosphorylation and other
      biomarkers in tumor tissue. The KTN3379 treatment duration is within the expected window of
      time that elapses from initial patient evaluation by a surgeon to performance of surgery.
      Paired preoperative and postoperative tumor specimen analyses allow evaluation of
      proliferation, ErbB3 related biomarkers, pErbB3 modulation and pharmacodynamic changes in
      downstream molecular pathways.
    

Trial Arms

NameTypeDescriptionInterventions
AExperimentalTreatment with KTN3379 in HPV positive head and neck cancer patients
  • KTN3379
BExperimentalTreatment with KTN3379 in HPV negative head and neck cancer patients
  • KTN3379

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed primary, untreated SCCHN including variants.
             Patients must be candidates for surgical resection. Primary tumors of oral cavity,
             oropharynx, hypopharnyx or larynx are included.

          2. Written informed consent and any locally required authorization (e.g., HIPAA in the
             USA) obtained from the patient/legal representative prior to performing any
             protocol-related procedures, including screening evaluations.

          3. Females of childbearing potential who are sexually active with a nonsterilized male
             partner must use 2 methods of effective contraception from screening, and must agree
             to continue using such precautions for 60 days after the final dose of KTN3379.
             Females of childbearing potential are defined as those who are not surgically sterile
             (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or
             those who are postmenopausal (defined as 12 months with no menses without an
             alternative medical cause)

          4. Nonsterilized males who are sexually active with a female partner of child-bearing
             potential must, with their partner, use 2 acceptable methods of effective
             contraception from Day 1 through 60 days after receipt of the final dose of KTN3379.

          5. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

          6. Adequate bone and marrow function as defined below:

               -  Hemoglobin ≥ 10 g/dL

               -  Absolute neutrophil count ≥ 1500/mm3

               -  Platelet count ≥ 100,000/mm3

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×ULN

               -  Bilirubin ≤ 1.5 × ULN except for cases of documented or suspected Gilbert's
                  disease, in which bilirubin must be ≤ 5 × ULN

               -  Serum creatinine ≤ 1.5 g/dL

               -  Normal PT or INR and aPTT

        Exclusion Criteria:

          1. Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy
             for cancer treatment.

          2. Immunosuppressive or systemic steroids medication within 7 days before the first dose
             of KTN3379 (inhaled and topical corticosteroids are permitted).

          3. Another invasive malignancy within 2 years prior to enrollment except for localized
             prostate cancer, cervical carcinoma in situ, non-melanomatous carcinoma of the skin,
             or ductal carcinoma in situ of the breast that has/have been surgically cured

          4. Major surgical procedure within 30 days prior to Day 1 or incomplete recovery from any
             prior surgery

          5. Pregnancy or lactation

          6. Uncontrolled intercurrent illness including but not limited to ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension,
             uncontrolled or idiopathic hypotension, unstable angina pectoris, cardiac arrhythmia
             including atrial fibrillation, significant cardiac conduction abnormalities including
             prolongation of QTc interval or BBB, active peptic ulcer disease or gastritis, or
             psychiatric illness/social situations that would limit compliance with study
             requirements or compromise the ability of the patient to give written informed consent

          7. Patients with a left ventricular cardiac ejection fraction < 50% as assessed by an
             echocardiogram or MUGA scan

          8. Patients with prior primary treatment for head and neck cancer (e.g. chemoradiation or
             radiation alone).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in pErbB3 levels in tumor tissue
Time Frame:4 weeks
Safety Issue:
Description:Reduction in pErbB3 levels

Secondary Outcome Measures

Measure:Number of patients with adverse events as a measure of safety and tolerability
Time Frame:6 weeks
Safety Issue:
Description:Adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, radiological assessments, vital signs, electrocardiograms (ECGs), and physical examinations.
Measure:Ki67 proliferative index in tumor tissue
Time Frame:4 weeks
Safety Issue:
Description:Ki67 proliferative index in tumor tissue before and after treatment
Measure:Changes in tumor measurements (RECIST 1.1 measurements)
Time Frame:4 weeks
Safety Issue:
Description:RECIST 1.1 measurements before and after treatment
Measure:Pharmacokinetics (Peak plasma concentrations of KTN3379 Trough plasma concentrations of KTN3379)
Time Frame:4 weeks
Safety Issue:
Description:Peak plasma concentrations of KTN3379 Trough plasma concentrations of KTN3379
Measure:Anti drug antibodies
Time Frame:6 weeks
Safety Issue:
Description:Measurement of anti KTN3379 antibodies in blood

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Celldex Therapeutics

Trial Keywords

  • CDX3379

Last Updated

August 1, 2019