Tipifarnib in Advanced Squamous NSCLC With Oncogen HRAS MutAtionS

NCT03496766 | Terminated Phase 2 Results

• 3 other identifiers: GECP17/04_THOMAS2017-004822-13KO-IST-003
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 30

Brief Summary

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.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response

  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. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions.

  From the first dose until progression disease, assessed from the first dose until the first assessment at week 6 from the first dose

Secondary Outcomes (2)

• Progression Free Survival

  From the start of treatment until first progression or death.

• Overall Survival

  From the date of randomization until end of follow up,up to 24 months

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Tipifarnib 600 mg, po, bid daily on days 1-7 and 15-21 of 28-day treatment cycles for up to 24 months

Drug: Tipifarnib

Interventions

Tipifarnib DRUG

Tipifarnib 600 mg will be administered until progression

Also known as: Zarnestra

Experimental Arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has a histologically or cytologically confirmed diagnosis of squamous non-small cell lung cancer (SQ-NSCLC) for which there is no curative therapy available.
• Subject has relapsed (progressive disease) or is refractory to one or more prior therapies. In the case of therapy received in the adjuvant or neo-adjuvant setting, relapse must have occurred within 12 months to be considered prior therapy. Subject may have received prior immunotherapy.
• Subject has a tumor that carries a missense HRAS mutation. HRAS status may have been assessed either in blood, primary tumor tissue, recurrent or metastatic disease.
• Subject has consented to provide tumor slides (or tumor tissue blocks) for biomarker evaluation. Before enrolment the site must confirm the availability of the tumor sample. If there is no sample available, the trial chair must be contacted for approval. If enrolment in the treatment portion of the study has taken place based on HRAS mutant status as assessed using a blood sample, tumor tissue must be sent before starting cycle 2 of treatment, and It will be used in part for confirmation of HRAS mutant tumor status. Confirmation of HRAS mutant status in tumor tissue is required for continuation of treatment. If HRAS mutation is not confirmed in tumor but is clearly positive in blood, the trial chair will be contacted for approval and the treatment could be maintained. All treated subjects will be evaluated for safety.
• \. At least 2 weeks since the last systemic therapy regimen prior to enrolment. Subjects must have recovered to NCI CTCAE v. 4.03 \< Grade 2 from all acute toxicities (excluding Grade 2 toxicities that are not considered a safety risk by the Sponsor and Investigator) or toxicity must be deemed irreversible by the Investigator.
• \. At least 2 weeks since last radiotherapy. If radiation was localized to the only site of measurable disease, there must be documentation of disease progression of the irradiated site. Subjects must have recovered from all acute toxicities from radiotherapy. Subjects may be on a daily dose of corticosteroids (≤ 20mg prednisone or equivalent), as part of their management from prior radiotherapy.
• \. ECOG (Eastern cooperative oncology group) performance status of 0 or 1. 9. Acceptable liver function:
• Bilirubin less than 1.5 times upper limit of normal (x ULN); does not apply to subjects with Gilbert's syndrome diagnosed as per institutional guidelines.
• AST Aspartate Amino-transferasa (SGOT) and ALT Aspartate-Alanina-transferase (SGPT) less than 3 x ULN; if liver metastases are present, then ≥ 5 x ULN is allowed.
• \. Acceptable renal function with serum creatinine less than 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault formula.
• \. Acceptable hematologic status:
• a. ANC (absolut neuthophil count) ≥ 1000 cells/μL. b. Platelet count ≥ 75,000/μL. c. Hemoglobin ≥ 9.0 g/dL. 12. Female subjects must be either:
• Of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal); or
• If of child-bearing potential, subject must use an adequate method of contraception consisting of two-barrier method or one barrier method with a spermicide or intrauterine device. Both females and male subjects with female partners of child-bearing potential must agree to use an adequate method of contraception for 2 weeks prior to screening, during, and at least 4 weeks after last dose of trial medication. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of trial medication.
• Not breast feeding at any time during the study. 13. Written and voluntary informed consent for the treatment phase understood, signed and dated.

You may not qualify if:

• Ongoing treatment with an anticancer agent not contemplated in this protocol.
• Prior treatment (at least 1 full treatment cycle) with an FTase inhibitor.
• Any history of clinically relevant coronary artery disease or myocardial infarction within the last 3 years, New York Heart Association (NYHA) grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or current 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).
• Non-tolerable \> Grade 2 neuropathy or evidence of emerging or rapidly progressing neurological symptoms within 4 weeks of Cycle 1 Day 1. Non-tolerable grade 2 toxicities are defined as those with moderate symptoms that the patient is not able to endure for the conduct of instrumental activities of daily life or that persists ≥ 7 days.
• Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1, 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.
• Subjects who have exhibited allergic reactions to tipifarnib or structural compounds similar to tipifarnib or to the drug product excipients. This includes hypersensitivity to imidazoles, such as clotrimazole, ketoconazole, miconazole and others in this drug class. Patients with hypersensitivity to these agents will be excluded from enrolment.
• Required use of concomitant medications classified as strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) or UDP-glucuronosyltransferase (UGT)
• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study.
• The subject has legal incapacity or limited legal capacity.
• Significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Unwillingness or inability to comply with the study protocol for any reason.

Sponsors & Collaborators

• Spanish Lung Cancer Group: lead

Study Sites (30)

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hospital Virgen de los Lirios

Alcoy, Alicante, 03804, Spain

Location

Hospital General Universitario de Elche

Elche, Alicante, 03203, Spain

Location

ICO-Badalona

Badalona, Barcelona, 08916, Spain

Location

ICO-Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Provincial de Castellón

Castellon, Castelló, 12002, Spain

Location

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, 28922, Spain

Location

Hospital Universitario de la Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Hospital Costa del Sol

Marbella, Málaga, 29603, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Central de Asturias

Oviedo, Principality of Asturias, Spain

Location

Hospital Sant Joan de Reus

Reus, Tarragona, 43204, Spain

Location

H. Universitario de Canarias

San Cristóbal de La Laguna, Tenerife, 38320, Spain

Location

H.U.Vall D´Hebrón

Barcelona, 08035, Spain

Location

H. Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario de Ciudad Real

Ciudad Real, 13005, Spain

Location

ICO Girona -H. Dr. Josep Trueta

Girona, 17007, Spain

Location

Hospital de Jaén

Jaén, 23007, Spain

Location

Hospital Lucus Agustí

Lugo, 27003, Spain

Location

Hospital La Princesa

Madrid, 28006, Spain

Location

Hospital Puerta de Hierro

Madrid, 28222, Spain

Location

H. 12 de Octubre

Madrid, Spain

Location

H. Carlos Haya

Málaga, 29010, Spain

Location

H. Son Llàtzer

Palma de Mallorca, 07198, Spain

Location

Hospital Clinico de Salamanca

Salamanca, 37007, Spain

Location

Hospital Virgen de La Macrena

Seville, 41009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

H. General U. de Valencia

Valencia, 46014, Spain

Location

Hospital La Fe

Valencia, Spain

Location

Related Links

• Web page of the sponsor where users can find more information about Fundación GECP studies

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The recruitment was closed prematurely to due to slow recruitment, so there are no consistent data to achieve any relevant conclusion at this point.

Results Point of Contact

• Title: Eva Pereira
• Organization: Fundación GECP

gecp@gecp.org

+34934302006

Study Officials

• Luis Paz Ares, MD

  Hospital 12 de Octubre

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2018
• First Posted: April 12, 2018
• Study Start: May 7, 2018
• Primary Completion: October 30, 2022
• Study Completion: November 9, 2022
• Last Updated: March 5, 2025
• Results First Posted: March 29, 2024

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (30)