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Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations

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ClinicalTrials.gov Identifier: NCT02383927
Recruitment Status : Recruiting
First Posted : March 10, 2015
Last Update Posted : May 9, 2019
Sponsor:
Information provided by (Responsible Party):
Kura Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE February 20, 2015
First Posted Date  ICMJE March 10, 2015
Last Update Posted Date May 9, 2019
Study Start Date  ICMJE March 2015
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2015)
Objective Response Rate (ORR) [ Time Frame: 24 months (approx. 12 months accrual + 12 months follow up) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02383927 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2015)
  • Progression-free Survival (PFS) [ Time Frame: 24 months (approx. 12 months accrual + 12 months follow up) ]
  • Duration of Response (DOR) [ Time Frame: 24 months (approx. 12 months accrual + 12 months follow up) ]
  • Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Until 30 days after the end of study ]
    Number of patients that experience Adverse Events (AEs). Adverse Events (AEs) and Serious Adverse Events (SAEs) will be graded according to the NCI-CTCAE (Version 4.03).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations
Official Title  ICMJE An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies With HRAS Mutations
Brief Summary Phase II study to investigate the antitumor activity in terms of objective response rate (ORR) of tipifarnib in subjects with advanced tumors that carry HRAS mutations and for whom there is no standard curative therapy available. Note; Only cohort 2 (Head & Neck SCC) and cohort 3 (Other SCC) are currently open
Detailed Description

This Phase II study will investigate the antitumor activity in terms of ORR of tipifarnib in subjects with locally advanced, unresectable or metastatic, relapsed and/or refractory tumors that carry HRAS mutations and for whom there is no curative therapy available. Subjects with information available on tumor HRAS status previously generated are eligible. All subjects must consent to provide at least 10 tumor slides from a prior diagnostic biopsy for a retrospective testing of HRAS gene status at a central facility.

Subjects will be enrolled into three nonrandomized cohorts:

  • Cohort 1: Malignant thyroid tumors with HRAS mutations (cohort is closed).
  • Cohort 2: Squamous Cell Carcinoma Head and Neck Cancer with HRAS mutations.
  • Cohort 3: Squamous Cell Carcinoma (SCC) with HRAS mutations other than HNSCC
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Thyroid Cancer
  • Squamous Cell Carcinoma Head and Neck Cancer (HNSCC)
  • HRAS Mutant Tumor
  • Other Squamous Cell Carcinoma (SCC) With HRAS Mutant Tumor
Intervention  ICMJE Drug: Tipifarnib
FTase inhibitor
Other Name: Zarnestra
Study Arms  ICMJE
  • Experimental: Cohort 1
    Thyroid Cancer
    Intervention: Drug: Tipifarnib
  • Experimental: Cohort 2
    Squamous Head and Neck Cancer
    Intervention: Drug: Tipifarnib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 7, 2019)
75
Original Estimated Enrollment  ICMJE
 (submitted: March 3, 2015)
36
Estimated Study Completion Date  ICMJE October 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • histologically or cytologically confirmed diagnosis of thyroid cancer (cohort 1: Note: Cohort closed to further enrolment) or Squamous Cell Carcinoma head and neck cancer (cohort 2) or Squamous Cell Carcinoma other than HNSCC (cohort 3) for which there is no curative therapy available.
  • tumor that carries a missense HRAS mutation ith a variant allele frequency (VAF) > 20%.
  • Subject consents to provide at least 10 unstained tumor slides for retrospective testing of HRAS gene tumor status
  • Subject has measurable disease according to RECIST v1.1 and has relapsed or is refractory to prior therapy.
  • At least 2 weeks since the last systemic therapy or radiotherapy regimen prior to enrolment
  • ECOG PS 0 or 1
  • Acceptable liver function
  • Acceptable renal function
  • Acceptable hematologic status • Serum albumin ≥ 3.5 g/dL. Subjects with tumors potentially highly sensitive to tipifarnib (HRAS mutant VAF ≥ 35%) may be enrolled despite a serum albumin < 3.5 g/dL.

Exclusion Criteria:

  • Prior treatment with an FTase inhibitor
  • History of relevant coronary heart disease or myocardial infarction within last 3 years, NYHA Grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or serious cardiac arrhythmia requiring medication except atrial fibrillation.
  • Known uncontrolled brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 4 weeks prior to Cycle 1 Day 1). Controlled brain metastases that require continuous high dose corticosteroid use within 4 weeks of Day 1.
  • Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks first dose
  • Major surgery, other than diagnostic surgery, within 4 weeks prior to first dose, without complete recovery.
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Known infection with HIV, or an active infection with hepatitis B or hepatitis C
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jeanne Britt 678-777-0686 medicalaffairs@kuraoncology.com
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Greece,   Italy,   Korea, Republic of,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02383927
Other Study ID Numbers  ICMJE KO-TIP-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Kura Oncology, Inc.
Study Sponsor  ICMJE Kura Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Kura Oncology, Inc.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP