Trials / Recruiting

RecruitingNCT05172245

Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer

Phase 1/1b Study of AKT Inhibitor Ipatasertib With Chemoradiation for Locally Advanced Head and Neck Cancer

Status: Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 46 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I/Ib trial tests the safety and best dose of ipatasertib in combination with the usual treatment approach using chemotherapy together with radiation therapy ("chemo-radiation") in patients with head and neck cancer. Ipatasertib is in a class of medications called protein kinase B (AKT) inhibitors. It may stop the growth of tumor cells and may kill them. Cisplatin, which is a chemotherapy used in this trial, is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Radiation therapy uses high energy to kill tumor cells and shrink tumors. Giving ipatasertib in combination with chemo-radiation may be better than chemo-radiation alone in treating patients with advanced head and neck cancer.

Detailed description

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ipatasertib in combination with definitive chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC) based on dose-limiting toxicities (DLTs). SECONDARY OBJECTIVES: I. To assess acute and late toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. II. To assess long-term swallowing function, based on gastric tube dependency at 6 and 12 months that is different from baseline. III. To determine duration and completion rate of prescribed radiation and chemotherapy. IV. To determine pharmacokinetic profile of ipatasertib in combination with cisplatin and radiation therapy, based on peak and trough blood levels in patients administered ipatasertib orally. V. To determine pharmacodynamic effects of ipatasertib at the MTD, based on pAKT, pS6 and pPRAS40 as markers of AKT pathway inhibition, and gamma-H2AX as a marker of radiosensitization. VI. To observe and record anti-tumor activity (objective response rate by Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria, locoregional control, relapse-free survival, and overall survival) of the combination of ipatasertib, cisplatin, and radiation therapy in patients with HNSCC. VII. To correlate efficacy outcomes with tumor genotype, based on whole exome sequencing of pre-treatment biopsy specimens. OUTLINE: This is a phase I, dose-escalation study of ipatasertib in combination with fixed-dose cisplatin and radiation therapy followed by a dose-expansion study. DOSE ESCALATION: Patients receive ipatasertib orally (PO) once daily (QD) or Monday, Wednesday, and Friday depending on dose level on days 1-28 of each cycle. Patients also receive cisplatin intravenously (IV) weekly on day 1 of cycle 1, weeks 1-4 and day 1 of cycle 2, weeks 1-3 for 7 doses. Patients undergo radiation therapy (RT) daily (Monday-Friday) for 35 fractions during weeks 1-7. Treatment repeats every 28 days for a total of 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET)/computed tomography (CT), CT, or magnetic resonance imaging (MRI) during screening, follow-up, and as clinically indicated. Patients undergo blood sample collection on trial. DOSE EXPANSION: Patients receive ipatasertib PO MTD on days 2-28 or 3-28 of cycle 1 and 1-28 of subsequent cycles. Patients also receive cisplatin IV weekly on day 1 of cycle 1, weeks 1-4 and day 1 of cycle 2, weeks 1-3 for 7 doses. Patients undergo RT daily (Monday-Friday) for 35 fractions during weeks 1-7. Treatment repeats every 28 days for a total of 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT, CT, or MRI during screening, follow-up, and as clinically indicated. Patients undergo blood sample collection and tumor biopsy on trial. After completion of study treatment, patients are followed for 30 days and then every 3 months for up to 2 years.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Cisplatin	Given IV
PROCEDURE	Computed Tomography	Undergo CT or PET/CT
DRUG	Ipatasertib	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
RADIATION	Radiation Therapy	Undergo radiation therapy

Timeline

Start date: 2022-09-19
Primary completion: 2027-07-01
Completion: 2027-07-01
First posted: 2021-12-29
Last updated: 2026-04-17

Locations

18 sites across 2 countries: United States, Canada

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05172245. Inclusion in this directory is not an endorsement.