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

NCT02383927 | Completed Phase 2 Results

• 1 other identifier: KO-TIP-001
• Study Type: interventional
• Target: 63
• Locations: 10 countries
• Sites: 35

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.

Conditions

Thyroid Cancer; Squamous Cell Carcinoma Head and Neck Cancer (HNSCC); HRAS Mutant Tumor; Other Squamous Cell Carcinoma (SCC) With HRAS Mutant Tumor

Outcome Measures

Primary Outcomes (1)

• Antitumor Activity by Objective Response Rate (ORR)

  The ORR of tipifarnib was response assessments according to RECIST 1.1. The estimate of the ORR was calculated based on the maximum likelihood estimator (i.e., crude percentage of subjects whose best overall response was complete response \[CR\] or partial response \[PR\]). The estimate of the ORR was accompanied by 2-sided 95% confidence interval (CI). The 95% CI was estimated using the Wilson score test-based method. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.

  Up to approximately 3 years

Secondary Outcomes (1)

• Number of Subjects That Experienced One or More Treatment-emergent Adverse Events (TEAEs)

  Up to approximately 3 years

Other Outcomes (4)

• Progression-free Survival (PFS)

  Up to approximately 3 years

• Duration of Response (DOR)

  Up to approximately 3 years

• Overall Survival (OS)

  Up to approximately 4 years

Study Arms (2)

Cohort 1

EXPERIMENTAL

Thyroid Cancer

Drug: Tipifarnib

Cohort 2

EXPERIMENTAL

Squamous Head and Neck Cancer

Drug: Tipifarnib

Interventions

Tipifarnib DRUG

FTase inhibitor

Also known as: Zarnestra

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• histologically or cytologically confirmed diagnosis of thyroid cancer (cohort 1) 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Kura Oncology, Inc.: lead

Study Sites (35)

University of California, Los Angeles

Los Angeles, California, 90404, United States

Location

Wihship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University Hospital Antwerp

Antwerp, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, Belgium

Location

CHU

Yvoir, Belgium

Location

Insitut Bergonie

Bordeaux, France

Location

Centre Léon Bérard

Lyon, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institute Gustave Roussy (IGR)

Paris, France

Location

University Hospital Wuerazburg

Würzburg, Germany

Location

Attikon University Hospital

Attiki, Greece

Location

Instituto Nazionale Tumori

Milan, Italy

Location

University Medical Center

Groningen, Netherlands

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Hospital Vall d' Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitario Doce de Octubre

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, Spain

Location

START, Centro Integral Oncologico Clara Campal

Madrid, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Complejo Hospitalario de Navarro

Navarro, Spain

Location

Hospital Universitario Virgen de la Rocio

Seville, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Spain

Location

Royal Marsden

London, England, United Kingdom

Location

University College Hospital

London, England, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33750196 DERIVED

MeSH Terms

Conditions

Thyroid Neoplasms; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Endocrine System Diseases; Thyroid Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Clinical Operations
• Organization: Kura Oncology, Inc.

KO-TIP-001@kuraoncology.com

+1 617-588-3755

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2015
• First Posted: March 10, 2015
• Study Start: May 13, 2015
• Primary Completion: December 14, 2020
• Study Completion: December 14, 2020
• Last Updated: July 11, 2024
• Results First Posted: July 11, 2024

Record last verified: 2024-07

Locations

NL (1); IT (1); US (9); GR (1); KR (2); GB (2); FR (4); BE (3); DE (1); ES (11)