Thyroid CancerPhase 2NCT02383927
Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations
A Phase 2 study testing Tipifarnib in people with Thyroid Cancer and Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), run by Kura Oncology, Inc. at 35 sites in 10 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thyroid Cancer, Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), HRAS Mutant Tumor
- What is being tested?
- Tipifarnib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 35 sitesin 10 countries
- Study dates
- 13 May 2015to 14 Dec 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
35 sites in 10 countries.
35 sites in 10 countries
Spain11 sites
Hospital Vall d' Hebron
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona
Hospital del Mar
Barcelona
Hospital Universitario Doce de Octubre
Madrid
Hospital Universitario La Paz
Madrid
MD Anderson Cancer Center Madrid
Madrid
START, Centro Integral Oncologico Clara Campal
Madrid
Hospital Universitario Virgen de la Victoria
Málaga
Complejo Hospitalario de Navarro
Navarro
Hospital Universitario Virgen de la Rocio
Seville
Hospital Universitario y Politécnico La Fe
Valencia
United States9 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Wihship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of California, Los Angeles
Los Angeles, California, 90404
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, 73104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
Mayo Clinic
Rochester, Minnesota, 55902
France4 sites
Insitut Bergonie
Bordeaux
Centre Léon Bérard
Lyon
Centre Antoine Lacassagne
Nice
Institute Gustave Roussy (IGR)
Paris
Belgium3 sites
University Hospital Antwerp
Antwerp
Cliniques universitaires Saint-Luc
Brussels
CHU
Yvoir
United Kingdom2 sites
Royal Marsden
London, England
University College Hospital
London, England
About this study
Official title: An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies With HRAS Mutations
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.
Read the 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 2: Squamous Cell Carcinoma Head and Neck Cancer with HRAS mutations.
- Cohort 3: Squamous Cell Carcinoma (SCC) with HRAS mutations other than HNSCC.
- Conditions
- Thyroid Cancer, Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), HRAS Mutant Tumor, Other Squamous Cell Carcinoma (SCC) With HRAS Mutant Tumor
- Being tested
- Tipifarnib
- Medical subject headings
- Thyroid Neoplasms, Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TipifarnibDrug
Also called Zarnestra
FTase inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Thyroid Cancer Receives: Drug: Tipifarnib |
| Cohort 2 | Experimental | Squamous Head and Neck Cancer Receives: Drug: Tipifarnib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to approximately 3 years
Secondary outcomes (1)
Number of Subjects That Experienced One or More Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started on or after the first dose of study drug and within 30 days of the last administration of study drug or immediately before the initiation of any other anticancer therapy. The Investigator was required to grade the severity/ intensity of each AE according to NCI-CTCAE version 4.03. If a severity/intensity of Grade 4 (life-threatening) or 5 (death) was applied to an AE, then the Investigator also reported the event as a serious AE.
Measured: Up to approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2015 (estimated)
- Study start13 May 2015
- Primary completion14 Dec 2020
- Study completion14 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thyroid CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kura Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02383927
- Sponsor's protocol ID
- KO-TIP-001
- Status last verified
- Jul 2024
- First submitted
- 20 Feb 2015
- Last updated
- 11 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 33750196
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies With HRAS Mutations
- ClinicalTrials.gov ID
- NCT02383927
- Acronym / sponsor ID
- KO-TIP-001
- Conditions
- Thyroid Cancer, Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), HRAS Mutant Tumor, Other Squamous Cell Carcinoma (SCC) With HRAS Mutant Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Kura Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 May 2015
- Primary completion
- 14 Dec 2020 (actual)
- Study completion
- 14 Dec 2020 (actual)
- First posted
- 10 Mar 2015 (estimated)
- Results
- Posted 11 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 2: Squamous Cell Carcinoma Head and Neck Cancer with HRAS mutations.
- Cohort 3: Squamous Cell Carcinoma (SCC) with HRAS mutations other than HNSCC.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: TipifarnibThyroid Cancer |
| Cohort 2 | Experimental | Drug: TipifarnibSquamous Head and Neck Cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TipifarnibAlso: ZarnestraFTase inhibitor | Drug | Cohort 1, Cohort 2 |
Primary outcome
Antitumor Activity by Objective Response Rate (ORR)
Time frame: Up to approximately 3 years
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.
1 secondary outcome
Number of Subjects That Experienced One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to approximately 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33750196Ho 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
35 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tipifarnib in people with Thyroid Cancer and Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), run by Kura Oncology, Inc. at 35 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in Spain, United States, France, Belgium, South Korea and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Antitumor Activity by Objective Response Rate (ORR) (time frame: Up to approximately 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02383927, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2024.