Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

AIM-HN

1. At least 18 years of age.

2. 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).

3. Documented tumor progression or recurrence from at least one prior platinum-containing regimen in the primary, neoadjuvant, adjuvant, advanced, recurrent or metastatic setting.

4. Known tumor missense HRAS mutation.

5. Measurable disease by RECIST v1.1.

6. ECOG performance status of 0-1.

7. Acceptable liver, renal and hematological function

Exclusion Criteria

  1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
  2. 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.
  3. Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
  4. 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.
  5. Received treatment for non-cancer related liver disease within prior year.

Inclusion Criteria: SEQ-HN

1. At least 18 years of age.

2. Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology.

3. Will or has received at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC.

4. HRAS wildtype (i.e., have no identified tumor missense HRAS mutation).

Exclusion Criteria: SEQ-HN

1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
AIM-HN
Tipifarnib, Oral Tablet. Dose Level 1 orally, bid on days 1-7 and 15-21 of 28-day treatment cycles
  • Drug: Tipifarnib
    Tablet for oral administration
  • Device: HRAS Detection Assay
    In Vitro Assay to detect HRAS mutations
No Intervention
SEQ-HN
To obtain historical information of first line therapy in subjects enrolled in AIM-HN, 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.

Recruiting Locations

University of Texas Health San Antonio - Mays Cancer Center
San Antonio, Texas 78229

More Details

Status
Recruiting
Sponsor
Kura Oncology, Inc.

Study Contact

Medical Affairs
617-588-3755
KO-TIP-007@kuraoncology.com

Detailed Description

KO-TIP-007 is an international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN) and the impact of HRAS mutations on response to first line systemic therapies for HNSCC (SEQ-HN). KO-TIP-007 has 2 study cohorts. The first study cohort, named AIM-HN, includes HNSCC subjects with HRAS mutations. AIM-HN subjects will receive treatment with tipifarnib and the outcome of this cohort will be evaluated for ORR by an independent review facility.

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 AIM-HN (HRAS mutant HNSCC) subjects 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.

HNSCC patients in whom HRAS mutations are identified and who meet eligibility criteria will be offered participation in AIM-HN. HNSCC patients in whom HRAS mutations are not identified may participate in SEQ-HN only. These patients will be followed and the comparison of outcomes of HRAS mutant and HRAS wild type HNSCC will address the exploratory objective to determine the effect of HRAS mutation on the ORR of first line systemic therapy in patients with recurrent/metastatic HNSCC. Outcome data from subsequent lines of therapy will be collected.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.