Clinical Trials List
Protocol NumberKO-TIP-007
NCT Number(ClinicalTrials.gov Identfier)NCT03719690
2019-05-01 - 2023-05-02
Phase II
Recruiting6
Terminated2
ICD-10C44.42
Squamous cell carcinoma of skin of scalp and neck
A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC) With HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN)
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
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Sponsor
Kura Oncology, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shang-Yin Wu 未分科
- 劉奕廷 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 廖斌志 無
- YA-FANG CHEN 無
- Hsiang-Fong Kao 無
- 黃彥霖 無
- HUAI-CHENG HUANG 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Head and Neck Squamous Cell Carcinoma (HNSCC)
Objectives
Primary Objective:
To determine the objective response rate (ORR) of tipifarnib in subjects with Head and Neck Squamous Cell Carcinoma (HNSCC) with HRAS mutations as assessed by Independent Review Facility (IRF).
Test Drug
Tipifarnib
Active Ingredient
Tipifarnib
Dosage Form
tablet
Dosage
300
Endpoints
Primary Endpoint
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.
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.
Inclution Criteria
Inclusion Criteria: AIM-HN
For inclusion of a subject in the tipifarnib treatment cohort of the study (AIM-HN), all of the
following inclusion criteria must be fulfilled:
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 with a variant allele frequency (VAF) > 20%
according to Next Generation Sequencing (NGS) or any other methodology approved by the
Sponsor. 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 performance status of 0-1.
9. Acceptable liver function:
a) Bilirubin 1.5 times upper limit of normal (x ULN).
b) AST (SGOT) and ALT (SGPT) 1.5 x ULN.
10. Acceptable renal function with either serum creatinine 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 hematologic status:
a) ANC 1000 cells/μL.
b) Platelet count 75,000/μL.
c) Hemoglobin 8.0 g/dL.
12. 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.
13. Female subjects must be: a) Of non-child-bearing potential (surgically sterilized or at least 2 years postmenopausal); 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 associated with inhibition of ovulation, intrauterine device,
intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised
partner or sexual abstinence. Both females and male subjects with female
partners of child-bearing potential must agree to use a highly effective method of
contraception from the first dose of tipifarnib, during tipifarnib treatment, and at
least 28 days after last dose of tipifarnib for females and 90 days for males.
Female subjects must have a negative serum or urine pregnancy test within 72
hours prior to start of trial medication.
c) Not breast feeding at any time during the study.
14. Written and voluntary informed consent understood, signed and dated by the study subject.
Inclusion Criteria: SEQ-HN
For inclusion of a subject in the noninterventional portion of the study (SEQ-HN), all of the
following inclusion criteria must be fulfilled:
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.
3. HRAS wildtype (i.e. have no identified tumor missense HRAS mutation) determined by a
test preferred by the site and approved by the Sponsor or through central HRAS
testing. HRAS status may be assessed on tumor obtained at primary diagnosis or at later
stages of disease.
4. Will or has received at least one systemic anti-cancer therapy for recurrent or metastatic
HNSCC for which there is available outcome information in terms of ORR, or the latter can
be estimated based on the subject’s records. Subjects who have not yet received or completed
at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC must consent to
the collection of treatment outcome information and additional follow up contact in order to
participate in the SEQ-HN portion of the study.
5. Written and voluntary informed consent understood, signed and dated by the study subject.
For inclusion of a subject in the tipifarnib treatment cohort of the study (AIM-HN), all of the
following inclusion criteria must be fulfilled:
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 with a variant allele frequency (VAF) > 20%
according to Next Generation Sequencing (NGS) or any other methodology approved by the
Sponsor. 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 performance status of 0-1.
9. Acceptable liver function:
a) Bilirubin 1.5 times upper limit of normal (x ULN).
b) AST (SGOT) and ALT (SGPT) 1.5 x ULN.
10. Acceptable renal function with either serum creatinine 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 hematologic status:
a) ANC 1000 cells/μL.
b) Platelet count 75,000/μL.
c) Hemoglobin 8.0 g/dL.
12. 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.
13. Female subjects must be: a) Of non-child-bearing potential (surgically sterilized or at least 2 years postmenopausal); 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 associated with inhibition of ovulation, intrauterine device,
intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised
partner or sexual abstinence. Both females and male subjects with female
partners of child-bearing potential must agree to use a highly effective method of
contraception from the first dose of tipifarnib, during tipifarnib treatment, and at
least 28 days after last dose of tipifarnib for females and 90 days for males.
Female subjects must have a negative serum or urine pregnancy test within 72
hours prior to start of trial medication.
c) Not breast feeding at any time during the study.
14. Written and voluntary informed consent understood, signed and dated by the study subject.
Inclusion Criteria: SEQ-HN
For inclusion of a subject in the noninterventional portion of the study (SEQ-HN), all of the
following inclusion criteria must be fulfilled:
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.
3. HRAS wildtype (i.e. have no identified tumor missense HRAS mutation) determined by a
test preferred by the site and approved by the Sponsor or through central HRAS
testing. HRAS status may be assessed on tumor obtained at primary diagnosis or at later
stages of disease.
4. Will or has received at least one systemic anti-cancer therapy for recurrent or metastatic
HNSCC for which there is available outcome information in terms of ORR, or the latter can
be estimated based on the subject’s records. Subjects who have not yet received or completed
at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC must consent to
the collection of treatment outcome information and additional follow up contact in order to
participate in the SEQ-HN portion of the study.
5. Written and voluntary informed consent understood, signed and dated by the study subject.
Exclusion Criteria
Exclusion Criteria: AIM-HN
A subject may not be enrolled in the tipifarnib treatment portion of the study (AIM-HN), if any
of the following exclusion criteria apply:
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 (excluding cholelithiasis) 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.
Exclusion Criteria: SEQ-HN
A subject may not be enrolled in the noninterventional portion of the study (SEQ-HN), if any of
the following exclusion criteria apply:
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 investigator, pose an unacceptable risk to the subject in this
study.
3. The subject has legal incapacity or limited legal capacity.
A subject may not be enrolled in the tipifarnib treatment portion of the study (AIM-HN), if any
of the following exclusion criteria apply:
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 (excluding cholelithiasis) 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.
Exclusion Criteria: SEQ-HN
A subject may not be enrolled in the noninterventional portion of the study (SEQ-HN), if any of
the following exclusion criteria apply:
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 investigator, pose an unacceptable risk to the subject in this
study.
3. The subject has legal incapacity or limited legal capacity.
The Estimated Number of Participants
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Taiwan
80 participants
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Global
300 participants
