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

Kura Oncology, Inc.45 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HNSCC

Interventions

TipifarnibDRUG

Oral administration

AlpelisibDRUG

Oral administration

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

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)

Outcomes

Primary Outcomes

Dose-limiting toxicity (DLT)

Rate of DLTs evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. A Treatment-Emergent Adverse Event (TEAE) is an AE occurring on or after Cycle 1 Day 1 and within 30 days of the last dose of tipifarnib or alpelisib, whichever is later. Patients with multiple events are counted only once at the highest CTCAE grade.

Time frame: First 28 days (1 cycle) of combination therapy

Descriptive statistics of Adverse Events (AEs)

Descriptive statistics of Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs; AE severity will be assessed per the NCI CTCAE v 5.0. AEs are coded using the MedDRA dictionary version 28.0. A TEAE is an AE occurring on or after Cycle 1 Day 1 and within 30 days of the last dose of tipifarnib or alpelisib, whichever is later. At each level of summation (system organ class, preferred term), a patient reporting more than one adverse event is counted only once.

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

Secondary Outcomes

Objective Response Rate (ORR)

Defined as the proportion of participants with best overall response as a confirmed complete response (CR) or confirmed partial response (PR) by RECIST v1.1. Clopper-Pearson 95% confidence intervals are calculated based on binomial distribution.

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

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. Median is calculated using Kaplan-Meier method. Confidence interval for median is calculated using the Brookmeyer-Crowley method. Minimum and maximum are actual values rather than estimates.

Data from ClinicalTrials.gov

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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

...and 1 more locations

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)

Disease control rate (CR + PR + SD)

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

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

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)

Defined as durable SD (\>= 12 weeks) by RECIST v1.1

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

Maximum observed concentration following single dose and multiple dose administration