Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) with HRAS Mutations MedDRA version: 20.0 Level: PT Classification code 10063569 Term: Metastatic squamous cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Tipifarnib 300 mg
Product Code: R115777
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tipifarnib
CAS Number
Sponsors
Kura Oncology, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: AIM-HN 1.At least 18 years of age. 2.Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Enrollment may proceed with local diagnosis but all subjects must consent to provide tumor tissue for a central pathology review. 3.Documented tumor progression or recurrence from at least one prior platinum-containing regimen in the primary, neoadjuvant, adjuvant, advanced, recurrent or metastatic setting. Subjects must have progressed or have recurred from a prior platinum containing regimen but there is no limit in the number of prior lines of therapy. Subjects without prior platinum treatment who, at the judgment of the investigator, are considered unsuitable to receive standard therapy with a platinum-containing regimen due to auditory deficit or hypersensitivity to platinum may be also enrolled. 4.Known tumor missense HRAS mutation. HRAS status may be assessed on tumor obtained at primary diagnosis or at later stages of disease. Enrollment may proceed with the identification of a missense HRAS mutation using a test preferred by the site and approved by the Sponsor but all subjects must consent to provide tumor tissue for central HRAS testing. Tumor tissue may be obtained from prior archival diagnostic biopsies. If no archival biopsy is available, a new biopsy will be required. 5.Measurable disease by RECIST v1.1 that meets the criteria for selection as a target lesion according to RECIST v1.1. The presence of at least one measurable target lesion per RECIST v1.1 must be confirmed by local radiology prior to subject entry. 6.At least 2 weeks since the last systemic therapy regimen prior to Cycle 1 Day 1. Subjects must have recovered to NCI CTCAE v5.0 < 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. 7.At least 2 weeks since last radiotherapy. Subjects must have recovered from all acute toxicities from radiotherapy. 8.ECOG perform. status of 0-2. 9.Acceptable liver function: a)Bilirubin less or equal 1.5 times upper limit of normal (x ULN); does not apply to subjects with Gilbert’s syndrome diagnosed as per institutional guidelines. b)AST (SGOT) and ALT (SGPT) less or equal 1.5 x ULN; 10.Acceptable renal function with either serum creatinine less or equal 1.5 x ULN or a calculated creatinine clearance = 60 mL/min using the Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formulas. 11.Acceptable hematol. status: a)ANC = 1000 cells/µL. b)Platelet count = 75,000/µL. c)Hemoglobin = 8.0 g/dL. 12.Female subjects must be: a)Of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal); or b)If of child-bearing potential, subject must use a highly effective method of contraception, such as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associate
Exclusion criteria
Exclusion criteria: AIM-HN 1.Has disease that is suitable for local therapy administered with curative intent. 2.Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma). 3.Known additional malignancy that is progressing or requires active treatment (excluding non-melanoma skin cancer, adjuvant hormonal therapy for breast cancer and hormonal treatment for castration sensitive prostate cancer). 4.Ongoing treatment with an anticancer agent not contemplated in this protocol (excluding adjuvant hormonal therapy for breast cancer and hormonal treatment for castration sensitive prostate cancer). 5.Prior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor (FTI). 6.Any use of investigational therapy within 2 weeks of Cycle 1 Day 1 or 5 half-lives (whichever is longer). 7.Received treatment for unstable angina within prior year, myocardial infarction within the prior year, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation. 8.Non-tolerable Grade 2 or = Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1. Non-tolerable Grade 2 toxicities are defined as those with moderate symptoms that the subject is not able to endure for the conduct of instrumental activities of daily life or that persists = 7 days. 9.Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery. 10.Active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy. Known history of infection with human immunodeficiency virus or an active infection with hepatitis B or hepatitis C. 11. Received treatment for non-cancer related liver disease within prior year. 12.Subjects who have exhibited allergic reactions to tipifarnib or structural compounds similar to tipifarnib or to its excipients. This includes hypersensitivity to imidazoles, such as clotrimazole, ketoconazole, miconazole and others in this drug class. Subjects with hypersensitivity to these agents will be excluded from enrollment. 13.Required use of concomitant medications classified as strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4, Table 7) or UDP-glucuronosyltransferase (UGT). 14.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. 15.Dementia or 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. 16.The subject has legal incapacity or limited legal capacity. SEQ-HN 1.Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma). 2.Concomitant disease or condition that could interfere with the conduct of the study or that would, in the opinion of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the ORR of tipifarnib in subjects with HNSCC with HRAS mutations as assessed by IRF.; Secondary Objective: To determine the anti-tumor activity of tipifarnib in terms of: time to response, DOR, TTP, PFS, one year progression free rate, one year survival and OS To investigate the safety and tolerability of tipifarnib according to the NCI CTCAE v5.0 To assess population PK of tipifarnib in subjects with HNSCC with HRAS mutations ;Primary end point(s): The primary endpoint is the proportion of subjects with confirmed Objective Response (OR), defined as either Complete Response (CR) or Partial Response (PR), calculated using the mITT analysis set.;Timepoint(s) of evaluation of this end point: Tumor response assessment visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Time to response •Duration of response (DOR) •Time to progression (TTP) •Progression-free survival (PFS) •1-year progression-free rate and 1-year survival rate •Overall survival rate (OS) •Adverse Events •Population PK parameters of tipifarnib •Laboratory test results •Vital Signs •ECG results ; Timepoint(s) of evaluation of this end point: Tumor response assessment visit End of response assessment visit Follow up visit | — |
Countries
Australia, Austria, Belgium, Canada, Denmark, France, Germany, Greece, Italy, Malaysia, Netherlands, Norway, Spain, Taiwan, Thailand, United Kingdom, United States
Contacts
Public ContactClinical Trials Mailbox
Kura Oncology, Inc.
Outcome results
None listed