---
title: Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)
nct_id: NCT04997902
overall_status: COMPLETED
phase: PHASE1, PHASE2
sponsor: Kura Oncology, Inc.
study_type: INTERVENTIONAL
primary_condition: HNSCC
countries: United States
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT04997902.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT04997902"
ct_last_update_post_date: 2025-12-23
last_seen_at: "2026-05-12T06:25:05.085Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

**Official Title:** 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

**NCT ID:** [NCT04997902](https://clinicaltrials.gov/study/NCT04997902)

## Key Facts

- **Status:** COMPLETED
- **Phase:** PHASE1, PHASE2
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 45
- **Lead Sponsor:** Kura Oncology, Inc.
- **Conditions:** HNSCC
- **Start Date:** 2021-12-07
- **Completion Date:** 2025-07-30
- **CT.gov Last Update:** 2025-12-23

## Brief Summary

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.

## Eligibility

- **Minimum age:** 18 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
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.
9. Other protocol defined inclusion criteria may apply.

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).
12. Other protocol defined exclusion criteria may apply.
```

## Arms

- **PIK3CA-dependent (Cohort 1)** (EXPERIMENTAL) — Adult participants with R/M HNSCC whose tumors harbor PI3KCA (activating) mutations and/or amplifications
- **HRAS-dependent (Cohort 2)** (EXPERIMENTAL) — Adult participants with R/M HNSCC whose tumors have increased HRAS dependency, defined as HRAS overexpression

## Interventions

- **Tipifarnib** (DRUG) — Oral administration
- **Alpelisib** (DRUG) — Oral administration

## Primary Outcomes

- **Dose-limiting toxicity (DLT)** _(time frame: First 28 days (1 cycle) of combination therapy)_ — Rate of DLTs per dose level
- **Descriptive statistics of Adverse Events (AEs)** _(time frame: 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)_ — Descriptive statistics of Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs; AE severity will be assessed per the NCI CTCAE v 5.0

## Secondary Outcomes

- **Objective Response Rate (ORR)** _(time frame: 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)_
- **Median duration of response** _(time frame: 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)_
- **Disease control rate (DCR)** _(time frame: 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)_
- **Median duration of Disease Control** _(time frame: 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)_
- **Rate of Stable Disease** _(time frame: 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)_
- **Median duration of Stable Disease (SD)** _(time frame: 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)_
- **Cmax of tipifarnib and alpelisib when administered in combination** _(time frame: 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.)_
- **Tmax of tipifarnib and alpelisib when administered in combination** _(time frame: 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.)_
- **AUC(0-last) of tipifarnib and alpelisib when administered in combination** _(time frame: 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.)_
- **AUC(tau) of tipifarnib and alpelisib when administered in combination** _(time frame: 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.)_
- **AUC(0-infinity) of tipifarnib and alpelisib when administered in combination** _(time frame: 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.)_
- **CL/F of tipifarnib and alpelisib when administered in combination** _(time frame: 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.)_
- **Vd/F of tipifarnib and alpelisib when administered in combination** _(time frame: 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.)_
- **Half-life of tipifarnib and alpelisib when administered in combination** _(time frame: 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.)_
- **Accumulation ratio of tipifarnib and alpelisib when administered in combination** _(time frame: 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.)_
- **Progression-free survival (PFS)** _(time frame: 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)_
- **Proportion of participants with PFS at 6 months** _(time frame: 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)_
- **Overall Survival (OS)** _(time frame: From Cycle 1 Day 1 until 3 years of treatment or death from any cause, whichever comes first)_
- **Proportion of patients with OS at 12 months** _(time frame: From Cycle 1 Day 1 until 12 months of treatment or death from any cause, whichever comes first)_

## Locations (11)

- City of Hope Comprehensive Cancer Center, Duarte, California, United States
- Lake Nona DDU (Florida Cancer Specialists), Orlando, Florida, United States
- University of Maryland School of Medicine (Marlene and Stewart Greenebaum Comprehensive Cancer Center), Baltimore, Maryland, United States
- Johns Hopkins University School of Medicine (Sidney Kimmel Comprehensive Cancer Center), Baltimore, Maryland, United States
- Dana-Farber Cancer Institute (Head and Neck Cancer Treatment Center), Boston, Massachusetts, United States
- Washington University, School of Medicine, St Louis, Missouri, United States
- Memorial Sloan Kettering Cancer Center, New York, New York, United States
- UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, United States
- UT Southwestern Medical Center (Harold C. Simmons Comprehensive Cancer Center), Dallas, Texas, United States
- University of Texas MD Anderson Cancer Center, Houston, Texas, United States
- University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, United States

## Recent Field Changes (last 30 days)

- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.city of hope comprehensive cancer center|duarte|california|united states` — added _(2026-05-12)_
- `locations.lake nona ddu (florida cancer specialists)|orlando|florida|united states` — added _(2026-05-12)_
- `locations.university of maryland school of medicine (marlene and stewart greenebaum comprehensive cancer center)|baltimore|maryland|united states` — added _(2026-05-12)_
- `locations.johns hopkins university school of medicine (sidney kimmel comprehensive cancer center)|baltimore|maryland|united states` — added _(2026-05-12)_
- `locations.dana-farber cancer institute (head and neck cancer treatment center)|boston|massachusetts|united states` — added _(2026-05-12)_
- `locations.washington university, school of medicine|st louis|missouri|united states` — added _(2026-05-12)_
- `locations.memorial sloan kettering cancer center|new york|new york|united states` — added _(2026-05-12)_
- `locations.upmc hillman cancer center|pittsburgh|pennsylvania|united states` — added _(2026-05-12)_
- `locations.ut southwestern medical center (harold c. simmons comprehensive cancer center)|dallas|texas|united states` — added _(2026-05-12)_
- `locations.university of texas md anderson cancer center|houston|texas|united states` — added _(2026-05-12)_
- `locations.university of wisconsin carbone cancer center|madison|wisconsin|united states` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT04997902.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT04997902*  
*This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*