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

Thyroid Cancer Clinical Trial

Official title:

An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies With HRAS Mutations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02383927
• Other study ID #: KO-TIP-001
• Status: Completed
• Phase: Phase 2
• Start date: March 2015
• Est. completion date: November 30, 2020

Study information

• Verified date: May 2021
• Source: Kura Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: November 30, 2020
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Tipifarnib
FTase inhibitor

Locations

Country	Name	City	State
Belgium	University Hospital Antwerp	Antwerp
Belgium	Cliniques universitaires Saint-Luc	Brussels
Belgium	CHU	Yvoir
France	Insitut Bergonie	Bordeaux
France	Centre Léon Bérard	Lyon
France	Centre Antoine Lacassagne	Nice
France	Institute Gustave Roussy (IGR)	Paris
Germany	University Hospital Wuerazburg	Würzburg
Greece	Attikon University Hospital	Attikí
Italy	Instituto Nazionale Tumori	Milan
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Netherlands	University Medical Center	Groningen
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall d' Hebron	Barcelona
Spain	Hospital Universitario Doce de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	START, Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Complejo Hospitalario de Navarro	Navarro
Spain	Hospital Universitario Virgen de la Rocio	Sevilla
Spain	Hospital Universitario y Politécnico La Fe	Valencia
United Kingdom	Royal Marsden	London	England
United Kingdom	University College Hospital	London	England
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Wihship Cancer Institute of Emory University	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California, Los Angeles	Los Angeles	California
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Oklahoma University Health Sciences Center	Oklahoma City	Oklahoma
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Kura Oncology, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Greece,  Italy,  Korea, Republic of,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)		24 months (approx. 12 months accrual + 12 months follow up)
Secondary	Progression-free Survival (PFS)		24 months (approx. 12 months accrual + 12 months follow up)
Secondary	Duration of Response (DOR)		24 months (approx. 12 months accrual + 12 months follow up)
Secondary	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).	Until 30 days after the end of study