Ignite Creation Date:
2025-12-25 @ 3:39 AM
Ignite Modification Date:
2025-12-26 @ 2:24 AM
Study NCT ID:
NCT04997902
Status:
COMPLETED
Last Update Posted:
2025-12-23
First Post:
2021-07-27
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000077195', 'term': 'Squamous Cell Carcinoma of Head and Neck'}, {'id': 'D009477', 'term': 'Hereditary Sensory and Autonomic Neuropathies'}, {'id': 'D012008', 'term': 'Recurrence'}, {'id': 'D006258', 'term': 'Head and Neck Neoplasms'}], 'ancestors': [{'id': 'D002294', 'term': 'Carcinoma, Squamous Cell'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009421', 'term': 'Nervous System Malformations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D011115', 'term': 'Polyneuropathies'}, {'id': 'D010523', 'term': 'Peripheral Nervous System Diseases'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D000013', 'term': 'Congenital Abnormalities'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C402769', 'term': 'tipifarnib'}, {'id': 'C585539', 'term': 'Alpelisib'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 45}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-12-07', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'nctId': 'NCT04809233', 'statusForNctId': 'AVAILABLE', 'hasExpandedAccess': True}, 'statusVerifiedDate': '2025-12', 'completionDateStruct': {'date': '2025-07-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-12-19', 'studyFirstSubmitDate': '2021-07-27', 'studyFirstSubmitQcDate': '2021-08-05', 'lastUpdatePostDateStruct': {'date': '2025-12-23', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2021-08-10', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-07-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Dose-limiting toxicity (DLT)', 'timeFrame': 'First 28 days (1 cycle) of combination therapy', 'description': 'Rate of DLTs per dose level'}, {'measure': 'Descriptive statistics of Adverse Events (AEs)', 'timeFrame': 'From Cycle 1 Day 1 until 30 days after last trial intervention dose or 30 days after trial completion, whichever comes first, assessed up to 2 years', 'description': 'Descriptive statistics of Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs; AE severity will be assessed per the NCI CTCAE v 5.0'}], 'secondaryOutcomes': [{'measure': 'Objective Response Rate (ORR)', 'timeFrame': 'From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years', 'description': 'Overall confirmed response rate (Complete Response or Partial Response)'}, {'measure': 'Median duration of response', 'timeFrame': 'From first documentation of response to first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years', 'description': 'Defined for participants with confirmed objective response as the time from the first documentation of response to the first documentation of disease progression by RECIST v1.1 or to death due to any cause before new anti-cancer treatment, whichever occurs first'}, {'measure': 'Disease control rate (DCR)', 'timeFrame': 'From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years', 'description': 'Disease control rate (CR + PR + SD)'}, {'measure': 'Median duration of Disease Control', 'timeFrame': 'From first documentation of response until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years', 'description': 'Defined for participants with confirmed objective response as the time in months from the first documentation of response to the first documentation of disease progression by RECIST v1.1 or to death due to any cause before new anti-cancer treatment, whichever occurs first, in patients with confirmed CR/PR'}, {'measure': 'Rate of Stable Disease', 'timeFrame': 'From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years'}, {'measure': 'Median duration of Stable Disease (SD)', 'timeFrame': 'From first documentation of response until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years', 'description': 'Defined as durable SD (\\>= 12 weeks) by RECIST v1.1'}, {'measure': 'Cmax of tipifarnib and alpelisib when administered in combination', 'timeFrame': 'Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.', 'description': 'Peak drug concentration for single dose and multiple dose'}, {'measure': 'Tmax of tipifarnib and alpelisib when administered in combination', 'timeFrame': 'Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.', 'description': 'Time to reach peak concentration following drug administration for single dose and multiple dose'}, {'measure': 'AUC(0-last) of tipifarnib and alpelisib when administered in combination', 'timeFrame': 'Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.', 'description': 'Area under the concentration-time curve from time zero to time of last measurable concentration for single dose and multiple dose'}, {'measure': 'AUC(tau) of tipifarnib and alpelisib when administered in combination', 'timeFrame': 'Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.', 'description': 'Area under the concentration-time curve during a dosage interval for single dose and multiple dose'}, {'measure': 'AUC(0-infinity) of tipifarnib and alpelisib when administered in combination', 'timeFrame': 'Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.', 'description': 'Area under the concentration-time curve from time zero to infinity for single dose'}, {'measure': 'CL/F of tipifarnib and alpelisib when administered in combination', 'timeFrame': 'Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.', 'description': 'Apparent total clearance of the drug after administration for single dose and multiple dose'}, {'measure': 'Vd/F of tipifarnib and alpelisib when administered in combination', 'timeFrame': 'Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.', 'description': 'Apparent volume of distribution after administration for single dose and multiple dose'}, {'measure': 'Half-life of tipifarnib and alpelisib when administered in combination', 'timeFrame': 'Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.', 'description': 'Time required for the amount of drug in the body to decrease by half for single dose and multiple dose'}, {'measure': 'Accumulation ratio of tipifarnib and alpelisib when administered in combination', 'timeFrame': 'Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.', 'description': 'Ratio of accumulation of a drug after multiple doses compared to a single dose'}, {'measure': 'Progression-free survival (PFS)', 'timeFrame': 'From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 3 years', 'description': 'Median PFS'}, {'measure': 'Proportion of participants with PFS at 6 months', 'timeFrame': 'From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 6 months', 'description': 'Proportion of participants alive and without progression at 6 months'}, {'measure': 'Overall Survival (OS)', 'timeFrame': 'From Cycle 1 Day 1 until 3 years of treatment or death from any cause, whichever comes first', 'description': 'Median OS; for patients with no events, OS will be censored at the last known to be alive date'}, {'measure': 'Proportion of patients with OS at 12 months', 'timeFrame': 'From Cycle 1 Day 1 until 12 months of treatment or death from any cause, whichever comes first', 'description': 'For patients with no events, OS will be censored at the last known to be alive date'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['HRAS', 'PIK3CA', 'PI3K', 'Tipifarnib', 'Alpelisib', 'R/M HNSCC (Recurrent/metastatic Head and Neck Squamous Cell Carcinoma)', 'Head and Neck Cancer', 'SCCHN'], 'conditions': ['HNSCC']}, 'descriptionModule': {'briefSummary': 'This phase 1/2 combination trial of tipifarnib, a farnesyltransferase inhibitor, and alpelisib, a PI3K inhibitor in participants with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors overexpress the HRAS protein and/or are PIK3CA-mutated and/or PIK3CA-amplified.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. At least 18 years of age.\n2. Histologically confirmed head and neck cancer of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).\n3. Documented treatment failure from at least 1 prior systemic therapy in the R/M setting, unless determined not appropriate.\n4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.\n5. Has a tumor that is dependent upon HRAS and/or PIK3CA.\n6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n7. Acceptable liver, renal, endocrine, and hematologic function.\n8. Must be able to swallow alpelisib whole tablet or oral suspension containing crushed tablets. Feeding tube may not be used for alpelisib administration.\n9. Other protocol defined inclusion criteria may apply.\n\nExclusion Criteria:\n\n1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (eg, mucosal melanoma).\n2. Ongoing treatment with certain anticancer agents.\n3. Prior treatment (at least 1 full treatment cycle) with an FTI or PI3K, mTOR, or AKT inhibitor.\n4. Received treatment for unstable angina, myocardial infarction, and/or cerebro-vascular attack within the prior 6 months.\n5. Non-tolerable Grade 2, or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.\n6. Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.\n7. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.\n8. Participant with an established diagnosis of diabetes mellitus Type 1 or not controlled Type 2.\n9. Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs based on Investigator discretion.\n10. Participant has currently documented pneumonitis/interstitial lung disease.\n11. Participant has a history of severe cutaneous reaction, such as Stevens-Johnson Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).\n12. Other protocol defined exclusion criteria may apply.'}, 'identificationModule': {'nctId': 'NCT04997902', 'briefTitle': 'Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Kura Oncology, Inc.'}, 'officialTitle': 'A Phase 1/2 Open-label, Biomarker-defined Cohort Trial to Evaluate the Safety, Determine the Recommended Combination Dosing, and Assess Early Antitumor Activity of Tipifarnib and Alpelisib for the Treatment of Adult Participants Who Have HRAS-overexpressing and/or PIK3CA-mutated and/or - Amplified Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma', 'orgStudyIdInfo': {'id': 'KO-TIP-013'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'PIK3CA-dependent (Cohort 1)', 'description': 'Adult participants with R/M HNSCC whose tumors harbor PI3KCA (activating) mutations and/or amplifications', 'interventionNames': ['Drug: Tipifarnib', 'Drug: Alpelisib']}, {'type': 'EXPERIMENTAL', 'label': 'HRAS-dependent (Cohort 2)', 'description': 'Adult participants with R/M HNSCC whose tumors have increased HRAS dependency, defined as HRAS overexpression', 'interventionNames': ['Drug: Tipifarnib', 'Drug: Alpelisib']}], 'interventions': [{'name': 'Tipifarnib', 'type': 'DRUG', 'description': 'Oral administration', 'armGroupLabels': ['HRAS-dependent (Cohort 2)', 'PIK3CA-dependent (Cohort 1)']}, {'name': 'Alpelisib', 'type': 'DRUG', 'otherNames': ['BYL719'], 'description': 'Oral administration', 'armGroupLabels': ['HRAS-dependent (Cohort 2)', 'PIK3CA-dependent (Cohort 1)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '91010', 'city': 'Duarte', 'state': 'California', 'country': 'United States', 'facility': 'City of Hope Comprehensive Cancer Center', 'geoPoint': {'lat': 34.13945, 'lon': -117.97729}}, {'zip': '32827', 'city': 'Orlando', 'state': 'Florida', 'country': 'United States', 'facility': 'Lake Nona DDU (Florida Cancer Specialists)', 'geoPoint': {'lat': 28.53834, 'lon': -81.37924}}, {'zip': '21201', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'University of Maryland School of Medicine (Marlene and Stewart Greenebaum Comprehensive Cancer Center)', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '21231', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins University School of Medicine (Sidney Kimmel Comprehensive Cancer Center)', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Dana-Farber Cancer Institute (Head and Neck Cancer Treatment Center)', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington University, School of Medicine', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '10065', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Memorial Sloan Kettering Cancer Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '15232', 'city': 'Pittsburgh', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'UPMC Hillman Cancer Center', 'geoPoint': {'lat': 40.44062, 'lon': -79.99589}}, {'zip': '75390', 'city': 'Dallas', 'state': 'Texas', 'country': 'United States', 'facility': 'UT Southwestern Medical Center (Harold C. Simmons Comprehensive Cancer Center)', 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'University of Texas MD Anderson Cancer Center', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '53792', 'city': 'Madison', 'state': 'Wisconsin', 'country': 'United States', 'facility': 'University of Wisconsin Carbone Cancer Center', 'geoPoint': {'lat': 43.07305, 'lon': -89.40123}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Kura Oncology, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}