Tipifarnib in Advanced Squamous NSCLC With Oncogen HRAS MutAtionS
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|ClinicalTrials.gov Identifier: NCT03496766|
Recruitment Status : Recruiting
First Posted : April 12, 2018
Last Update Posted : November 25, 2019
This Phase II study consists of 2 parts: 1) pre-screening phase and 2) treatment phase.
The pre-screening phase will investigate the presence of HRAS mutations in subjects with a histologically or cytologically confirmed diagnosis of squamous non-small cell lung cancer (SQ-NSCLC). Subjects may participate in the pre-screening phase at initial diagnosis or following prior lines of therapy for SQ-NSCLC.
The treatment phase will investigate the antitumor activity in terms of ORR of tipifarnib in subjects with locally advanced squamous non-small cell lung cancer (SQ-NSCLC) with HRAS mutations and for whom there is no curative therapy available.
|Condition or disease||Intervention/treatment||Phase|
|Non Small Cell Lung Cancer||Drug: Tipifarnib||Phase 2|
Subject enrolment may proceed with information available on tumor HRAS status previously generated during the pre-screening phase, but all subjects must consent to provide tumor slides (or tumor tissue block) from a prior diagnostic biopsy for a retrospective testing of RAS gene status, including T81C polymorphism, and other potential biomarkers at a central facility.
Tipifarnib will be administered at a starting dose of 600 mg, po, bid daily on days 1-7 and 15-21 of 28-day treatment cycles. In the absence of unmanageable toxicities, subjects may continue to receive tipifarnib treatment for up to 24 months in the absence of disease progression and unmanageable toxicity. Treatment may continue beyond 24 months if there is documented evidence of continued clinical benefit.
Tumor assessments will be performed at screening and approximately every 8 weeks for the first 6 months (cycles 2, 4, 6) and then every 12 weeks (cycles 9, 12, 15, etc.) until disease progression, starting at the end of Cycle 2. Additional tumor assessments may be conducted if deemed necessary by the Investigator or for a confirmation of an objective response. Subjects who discontinue tipifarnib treatment for reasons other than disease progression must continue tumor assessments until disease progression, withdrawal of subject's consent to study procedures or initiation of another anticancer therapy.
Determination of objective tumor response will be performed by the Investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Electronic copies of tumor images may be de-identified of subject's personal information at the clinical sites and collected by the Sponsor to undergo an external independent radiological review if the sponsor deems it necessary for the final assessment of treatment efficacy. Subjects with a solitary site of disease who have experienced a response may be considered for surgical resection. Subjects with a best response of a partial response and residual disease after salvage surgery will be eligible to continue on study therapy. Information on the duration of response to the last prior therapy will be collected.
Upon disease progression, subjects will be followed approximately every 12 weeks for survival until either death or 24 months after accrual in the subject's study cohort has been completed, whichever occurs first. Information on subsequent anticancer therapy will be collected.
All subjects will be followed-up for safety during treatment and for approximately 30 additional days after treatment discontinuation (or until immediately before the administration of another anticancer treatment). Additional safety follow up may be conducted if unresolved toxicity is present at the End of Treatment visit.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open Label Phase II Study of Tipifarnib in Advanced Squamous Non-small Cell Lung Cancer With HRAS Mutations|
|Actual Study Start Date :||May 7, 2018|
|Estimated Primary Completion Date :||May 30, 2021|
|Estimated Study Completion Date :||May 30, 2022|
Experimental: Experimental Arm
Tipifarnib 600 mg, po, bid daily on days 1-7 and 15-21 of 28-day treatment cycles for up to 24 months
Tipifarnib 600 mg will be administered until progression
Other Name: Zarnestra
- Overall Response Rate [ Time Frame: From the first dose until progression disease, assessed from the first dose until the first assessment at week 6 from the first dose ]To determine the antitumor activity in terms of objective response rate (ORR) of tipifarnib in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, squamous non-small cell lung cancer (SQ-NSCLC) with HRAS mutations
- Frequency of HRAS mutations [ Time Frame: at the beginning of the study, day -7 to day 0 ]As there is a screening phase where HRAS mutations will be analyzed, the second outcome is to determine the frequency (%) of this mutation in the target population of this study
- Tolerability as Incidence of Treatment-Emergent Adverse Events of Tipifarnib [ Time Frame: from the first dose of treatment until 30 days after the last dose of treatment ]Adverse events will be collected in all the patients in order to now the tolerability of the treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03496766
|Contact: Santiago Ponce, MDemail@example.com|
|Contact: Eva Pereirafirstname.lastname@example.org|
|Study Chair:||Luis Paz Ares, MD||Hospital 12 de Octubre|