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

Primary Purpose

Thyroid Cancer, Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), HRAS Mutant Tumor

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tipifarnib
Sponsored by
Kura Oncology, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thyroid Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, Los Angeles
  • Wihship Cancer Institute of Emory University
  • Dana-Farber Cancer Institute
  • University of Michigan Comprehensive Cancer Center
  • Mayo Clinic
  • Memorial Sloan-Kettering Cancer Center
  • Oklahoma University Health Sciences Center
  • Fox Chase Cancer Center
  • The University of Texas MD Anderson Cancer Center
  • University Hospital Antwerp
  • Cliniques universitaires Saint-Luc
  • CHU
  • Insitut Bergonie
  • Centre Léon Bérard
  • Centre Antoine Lacassagne
  • Institute Gustave Roussy (IGR)
  • University Hospital Wuerazburg
  • Attikon University Hospital
  • Instituto Nazionale Tumori
  • Asan Medical Center
  • Samsung Medical Center
  • University Medical Center
  • Hospital Vall d' Hebron
  • Hospital Clinic de Barcelona
  • Hospital del Mar
  • Hospital Universitario Doce de Octubre
  • Hospital Universitario La Paz
  • MD Anderson Cancer Center Madrid
  • START, Centro Integral Oncologico Clara Campal
  • Hospital Universitario Virgen de la Victoria
  • Complejo Hospitalario de Navarro
  • Hospital Universitario Virgen de la Rocio
  • Hospital Universitario y Politécnico La Fe
  • Royal Marsden
  • University College Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Arm Description

Thyroid Cancer

Squamous Head and Neck Cancer

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)

Secondary Outcome Measures

Progression-free Survival (PFS)
Duration of Response (DOR)
Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs)
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).

Full Information

First Posted
February 20, 2015
Last Updated
May 12, 2021
Sponsor
Kura Oncology, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02383927
Brief Title
Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations
Official Title
An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies With HRAS Mutations
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
November 30, 2020 (Actual)
Study Completion Date
November 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kura Oncology, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thyroid Cancer, Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), HRAS Mutant Tumor, Other Squamous Cell Carcinoma (SCC) With HRAS Mutant Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Thyroid Cancer
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Squamous Head and Neck Cancer
Intervention Type
Drug
Intervention Name(s)
Tipifarnib
Other Intervention Name(s)
Zarnestra
Intervention Description
FTase inhibitor
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Time Frame
24 months (approx. 12 months accrual + 12 months follow up)
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Time Frame
24 months (approx. 12 months accrual + 12 months follow up)
Title
Duration of Response (DOR)
Time Frame
24 months (approx. 12 months accrual + 12 months follow up)
Title
Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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).
Time Frame
Until 30 days after the end of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Wihship Cancer Institute of Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Oklahoma University Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111-2497
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University Hospital Antwerp
City
Antwerp
Country
Belgium
Facility Name
Cliniques universitaires Saint-Luc
City
Brussels
Country
Belgium
Facility Name
CHU
City
Yvoir
Country
Belgium
Facility Name
Insitut Bergonie
City
Bordeaux
Country
France
Facility Name
Centre Léon Bérard
City
Lyon
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
Country
France
Facility Name
Institute Gustave Roussy (IGR)
City
Paris
Country
France
Facility Name
University Hospital Wuerazburg
City
Würzburg
Country
Germany
Facility Name
Attikon University Hospital
City
Attikí
Country
Greece
Facility Name
Instituto Nazionale Tumori
City
Milan
Country
Italy
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
University Medical Center
City
Groningen
Country
Netherlands
Facility Name
Hospital Vall d' Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario Doce de Octubre
City
Madrid
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain
Facility Name
MD Anderson Cancer Center Madrid
City
Madrid
Country
Spain
Facility Name
START, Centro Integral Oncologico Clara Campal
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Virgen de la Victoria
City
Málaga
Country
Spain
Facility Name
Complejo Hospitalario de Navarro
City
Navarro
Country
Spain
Facility Name
Hospital Universitario Virgen de la Rocio
City
Sevilla
Country
Spain
Facility Name
Hospital Universitario y Politécnico La Fe
City
Valencia
Country
Spain
Facility Name
Royal Marsden
City
London
State/Province
England
Country
United Kingdom
Facility Name
University College Hospital
City
London
State/Province
England
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33750196
Citation
Ho AL, Brana I, Haddad R, Bauman J, Bible K, Oosting S, Wong DJ, Ahn MJ, Boni V, Even C, Fayette J, Flor MJ, Harrington K, Kim SB, Licitra L, Nixon I, Saba NF, Hackenberg S, Specenier P, Worden F, Balsara B, Leoni M, Martell B, Scholz C, Gualberto A. Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations. J Clin Oncol. 2021 Jun 10;39(17):1856-1864. doi: 10.1200/JCO.20.02903. Epub 2021 Mar 22. Erratum In: J Clin Oncol. 2021 Oct 1;39(28):3192.
Results Reference
derived

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

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