Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

NCT ID: NCT04997902

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-07

Study Completion Date

2025-07-30

Brief Summary

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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.

Detailed Description

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Conditions

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HNSCC

Keywords

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HRAS PIK3CA PI3K Tipifarnib Alpelisib R/M HNSCC (Recurrent/metastatic Head and Neck Squamous Cell Carcinoma) Head and Neck Cancer SCCHN

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PIK3CA-dependent (Cohort 1)

Adult participants with R/M HNSCC whose tumors harbor PI3KCA (activating) mutations and/or amplifications

Group Type EXPERIMENTAL

Tipifarnib

Intervention Type DRUG

Oral administration

Alpelisib

Intervention Type DRUG

Oral administration

HRAS-dependent (Cohort 2)

Adult participants with R/M HNSCC whose tumors have increased HRAS dependency, defined as HRAS overexpression

Group Type EXPERIMENTAL

Tipifarnib

Intervention Type DRUG

Oral administration

Alpelisib

Intervention Type DRUG

Oral administration

Interventions

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Tipifarnib

Oral administration

Intervention Type DRUG

Alpelisib

Oral administration

Intervention Type DRUG

Other Intervention Names

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BYL719

Eligibility Criteria

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Inclusion Criteria

1. At least 18 years of age.
2. 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).
3. Documented treatment failure from at least 1 prior systemic therapy in the R/M setting, unless determined not appropriate.
4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
5. Has a tumor that is dependent upon HRAS and/or PIK3CA.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Acceptable liver, renal, endocrine, and hematologic function.
8. Must be able to swallow alpelisib whole tablet or oral suspension containing crushed tablets. Feeding tube may not be used for alpelisib administration.

Exclusion Criteria

1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (eg, mucosal melanoma).
2. Ongoing treatment with certain anticancer agents.
3. Prior treatment (at least 1 full treatment cycle) with an FTI or PI3K, mTOR, or AKT inhibitor.
4. Received treatment for unstable angina, myocardial infarction, and/or cerebro-vascular attack within the prior 6 months.
5. Non-tolerable Grade 2, or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
6. Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
7. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
8. Participant with an established diagnosis of diabetes mellitus Type 1 or not controlled Type 2.
9. Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs based on Investigator discretion.
10. Participant has currently documented pneumonitis/interstitial lung disease.
11. 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kura Oncology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Lake Nona DDU (Florida Cancer Specialists)

Orlando, Florida, United States

Site Status

University of Maryland School of Medicine (Marlene and Stewart Greenebaum Comprehensive Cancer Center)

Baltimore, Maryland, United States

Site Status

Johns Hopkins University School of Medicine (Sidney Kimmel Comprehensive Cancer Center)

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute (Head and Neck Cancer Treatment Center)

Boston, Massachusetts, United States

Site Status

Washington University, School of Medicine

St Louis, Missouri, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

UT Southwestern Medical Center (Harold C. Simmons Comprehensive Cancer Center)

Dallas, Texas, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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KO-TIP-013

Identifier Type: -

Identifier Source: org_study_id