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Clinical Trial 19855

Cancer Type: Head & Neck
Interventions:Zarnestra (tipifarnib); tipifarnib

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Christine Chung

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

The AIM-HN and SEQ-HN Study: A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients with Head and Neck Squamous Cell Carcinoma(HNSCC) with HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN).

Summary

This is an international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN). The first cohort will assess the objective response rate (ORR) of tipifarnib in subjects with HNSCC with HRAS mutations. The second study cohort, SEQ-HN, is an observational sub-study and includes 2 types of patients: (1) the historical record of first line therapy in subjects with HRAS mutant HNSCC participating in Cohort 1 in whom first line outcome data are available and (2) matched control HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.

Objective

Primary Objective: To determine the ORR of tipifarnib in subjects with HNSCC with HRAS mutations as assessed by IRF. Secondary Objectives: To determine the anti-tumor activity of tipifarnib in terms of: time to response, DOR, TTP, PFS, one year progression free rate, one year survival and OS. To investigate the safety and tolerability of tipifarnib according to the NCI CTCAE v5.0. To assess population PK of tipifarnib in subjects with HNSCC with HRAS mutations. Exploratory Objectives: To identify HRAS mutations and assess their effect on the ORR of first line systemic therapy in patients with recurrent/metastatic HNSCC. To assess the treatment outcome to first line systemic therapy in terms of PFS, DOR, and OS in patients with recurrent/metastatic HNSCC with HRAS mutations. To describe demographic characteristics prevalent in patients with HNSCC with HRAS mutations. To explore the frequency and treatment outcome interaction of other HNSCC genetic alterations. To identify trends in the data that may suggest relationships between covariates of interest and treatment outcome in patients with HNSCC with HRAS mutations.

Inclusion Criteria

  • At least 18 years of age.
  • Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
  • Documented tumor progression or recurrence from at least one prior platinum-containing regimen in the primary, neoadjuvant, adjuvant, advanced, recurrent or metastatic setting.
  • Known tumor missense HRAS mutation.
  • Measurable disease by RECIST v1.1.
  • ECOG performance status of 0-2.
  • Acceptable liver, renal and hematological function
  • Inclusion Criteria: SEQ-HN
  • At least 18 years of age.
  • Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology.
  • Will or has received at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC.

  • Exclusion Criteria

  • Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
  • Received treatment for unstable angina within prior year, myocardial infarction within the prior year, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
  • Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
  • Active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy. Known history of infection with human immunodeficiency virus or an active infection with hepatitis B or hepatitis C.
  • Received treatment for non-cancer related liver disease within prior year.
  • Exclusion Criteria: SEQ-HN
  • Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).