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

A Window of Opportunity Study of KTN3379 in Surgically Resectable Head and Neck <span class="go-doc-concept go-doc-disease">Cancer</span> Patients

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

    NCT ID: NCT02473731

    ORG ID: KTN3379-CL-002

    Trial Conditions

    Squamous Cell Carcinoma of the Head and Neck

    Trial Interventions

    Drug Synonyms Arms

    Trial 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

    Name Type Description Interventions
    A Experimental Treatment with KTN3379 in HPV positive head and neck cancer patients
    B Experimental Treatment with KTN3379 in HPV negative head and neck cancer patients

    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).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Change in pErbB3 levels in tumor tissue

    Secondary Outcome Measures

    Number of patients with adverse events as a measure of safety and tolerability

    Ki67 proliferative index in tumor tissue

    Changes in tumor measurements (RECIST 1.1 measurements)

    Pharmacokinetics (Peak plasma concentrations of KTN3379 Trough plasma concentrations of KTN3379)

    Anti drug antibodies

    Trial Keywords