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Trial record 1 of 1 for:    NCT03719690
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Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy (AIM-HN/SEQ-HN)

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ClinicalTrials.gov Identifier: NCT03719690
Recruitment Status : Active, not recruiting
First Posted : October 25, 2018
Last Update Posted : November 9, 2022
Sponsor:
Information provided by (Responsible Party):
Kura Oncology, Inc.

Study Description
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Brief Summary:
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 including 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.

Condition or disease Intervention/treatment Phase
HRAS Gene Mutation HNSCC Drug: Tipifarnib Device: HRAS Detection Assay Phase 2

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 including 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 284 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : November 5, 2018
Estimated Primary Completion Date : May 30, 2023
Estimated Study Completion Date : May 31, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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
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.


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate in High Variable Allele Frequency (VAF) population [ Time Frame: 2 years ]
    complete response and partial response


Secondary Outcome Measures :
  1. Objective Response Rate in any VAF population [ Time Frame: 2 years ]
    Determine anti-tumor activity of tipifarnib

  2. Duration of Response in High VAF population [ Time Frame: 2 years ]
    Determine anti-tumor activity of tipifarnib

  3. Duration of Response in any VAF population [ Time Frame: 2 years ]
    Determine anti-tumor activity of tipifarnib

  4. Progression Free Survival in both high VAF and all VAF populations [ Time Frame: 6 and 9 months ]
    Determine anti-tumor activity of tipifarnib

  5. Overall survival in both high VAF and all VAF populations [ Time Frame: 1 year ]
    Determine anti-tumor activity of tipifarnib

  6. Overall survival in both high VAF and all VAF populations [ Time Frame: 2 years ]
    Determine anti-tumor activity of tipifarnib

  7. Investigate safety and tolerability of tipifarnib according to NCI CTCAE v5.0 [ Time Frame: 30 days after treatment discontinuation ]
    Incidence of adverse events, incidence of abnormal laboratory test results, abnormal vital signs, and abnormal ECG results

  8. Time to Response in both high VAF and all VAF populations [ Time Frame: 2 years ]
    Determine anti-tumor activity of tipifarnib

  9. Time to Progression in both high VAF and all VAF populations [ Time Frame: 2 years ]
    Determine anti-tumor activity of tipifarnib

  10. Investigate effects of tipifarnib treatment on quality of life using EORTC QLQ-H&N35 [ Time Frame: 2 years ]
    Measured by changes of quality of life using the EORTC QLQ-H&N35

  11. Evaluate the concentration of tipifarnib [pharmacokinetics (PK)] in blood samples over time [ Time Frame: 6 months ]
    Measured by blood samples collected during the first 6 cycles of treatment

  12. Investigate effects of tipifarnib treatment on quality of life using EQ-5D-5L [ Time Frame: 2 years ]
    Measured by changes of quality of life using the EQ-5D-5L.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 treatment failure from most recent prior therapy (e.g. tumor progression, clinical deterioration, or recurrence), and from at least one prior platinum-containing regimen, in any treatment 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
  8. Other protocol defined inclusion criteria may apply.

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.
  6. Other protocol defined exclusion criteria may apply

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).
  5. Other protocol defined inclusion criteria may apply

Exclusion Criteria: SEQ-HN

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

5. Other protocol defined exclusion criteria may apply

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03719690


Locations
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Sponsors and Collaborators
Kura Oncology, Inc.
More Information
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Responsible Party: Kura Oncology, Inc.
ClinicalTrials.gov Identifier: NCT03719690    
Other Study ID Numbers: KO-TIP-007
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: November 9, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kura Oncology, Inc.:
TIPIFARNIB
HEAD AND NECK CANCER
Additional relevant MeSH terms:
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Squamous Cell Carcinoma of Head and Neck
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
 Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Tipifarnib
Antineoplastic Agents