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

HNSCC Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04997902
• Other study ID #: KO-TIP-013
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 7, 2021
• Est. completion date: September 2024

Study information

• Verified date: October 2023
• Source: Kura Oncology, Inc.
• Contact: Clinical Operations
• Phone: 617-588-3755
• Email: KO-TIP-013[@]kuraoncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• HNSCC
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Tipifarnib
Oral administration
• Alpelisib
Oral administration

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Kura Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the recommended dose and regimen and evaluate the safety and tolerability of the combination of tipifarnib and alpelisib	Rate of DLT per dose level and Descriptive statistics of adverse events per the NCI CTCAE v 5.0	DLTs will be evaluated during the first 28 days (1 cycle) of combination therapy
Secondary	Determine the Objective Response Rate (ORR)	Overall confirmed response rate (CR + PR) and Median duration of response	Up to approximately 3 years
Secondary	Disease control rate (DCR)	Disease control rate (CR + PR + SD), Median duration of disease control, Rate of SD, Median duration of SD	Up to approximately 3 years
Secondary	Cmax of tipifarnib and alpelisib when administered in combination	Peak drug concentration for single dose and multiple dose	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.
Secondary	Tmax of tipifarnib and alpelisib when administered in combination	Time to reach peak concentration following drug administration for single dose and multiple dose	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.
Secondary	AUC(0-last) of tipifarnib and alpelisib when administered in combination	Area under the concentration-time curve from time zero to time of last measurable concentration for single dose and multiple dose	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.
Secondary	AUC(tau) of tipifarnib and alpelisib when administered in combination	Area under the concentration-time curve during a dosage interval for single dose and multiple dose	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.
Secondary	AUC(0-infinity) of tipifarnib and alpelisib when administered in combination	Area under the concentration-time curve from time zero to infinity for single dose	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.
Secondary	CL/F of tipifarnib and alpelisib when administered in combination	Apparent total clearance of the drug after administration for single dose and multiple dose	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.
Secondary	Vd/F of tipifarnib and alpelisib when administered in combination	Apparent volume of distribution after administration for single dose and multiple dose	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.
Secondary	Half-life of tipifarnib and alpelisib when administered in combination	Time required for the amount of drug in the body to decrease by half for single dose and multiple dose	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.
Secondary	Accumulation ratio of tipifarnib and alpelisib when administered in combination	Ratio of accumulation of a drug after multiple doses compared to a single dose	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.
Secondary	Antitumor activity in terms of PFS and rate of PFS at 6 months	Median PFS and Proportion of participants alive and without progression at 6 months	Up to approximately 3 years
Secondary	Overall Survival (OS) and rate of OS at 12 months	Median OS and Proportion of participants alive at 12 months	Up to approximately 3 years