FID-007 Followed by Standard of Care Surgery in Head and Neck Cancer

Phase 1TerminatedNCT06338657

University of Southern California1 enrolled

Overview

This phase I trial studies on how the PEOX-based polymer encapsulated paclitaxel FID-007 (FID-007) affects the immune cells around the tumor patients with head and neck squamous cell carcinoma. The active drug in FID-007 is paclitaxel, an established chemotherapy drug that has been shown to kill cancer cells. FID-007 is a packaged form of paclitaxel using a polyethylozaxoline (PEOX) polymer which may allow the drug to reach deeper into tumors and less into normal cells by being smaller. This study is being done to help identify future treatment options and better understand how to improve outcomes of patients with head and neck cancers after surgery.

PRIMARY OBJECTIVE: I. To describe the phenotypical and functional changes of different T cell subsets within the tumor microenvironment after treatment with FID-007. SECONDARY OBJECTIVES: I. To describe the adverse events associated with neoadjuvant FID-007 prior to surgery for head and neck cancer. II. To evaluate preliminary evidence of efficacy by describing the rate of major and complete pathologic response. III. To describe the rates of locoregional recurrence and rate of distant metastasis at 2 years after surgery. EXPLORATORY OBJECTIVE: I. Explore association between pathologic response and phenotypical and functional changes in T cell subsets. OUTLINE: Patients receive FID-007 intravenously (IV) over 30 minutes once a week for 3 weeks on days 1, 8, and 15 of a single 28 day cycle in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients must have histopathologically / cytologically confirmed diagnosis of head and neck squamous cell carcinoma * Sites of primary tumor allowed include the oral cavity and oropharynx only. Patients with recurrent disease that is amenable to surgery are eligible * Patients may have any stage cancer amenable to surgical resection * Patients must be able to provide an archival tissue specimen. Excisional biopsy or core needle biopsy specimens are allowed. Fine needle aspiration samples are not acceptable * Patients with oropharynx cancer must have p16 negative disease * Age ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Leukocytes ≥ 3,000/mcL * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcl * Hemoglobin ≥ 9 g/dl * Total bilirubin ≤ 1.5 X institutional upper limit of normal * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 X institutional upper limit of normal * Creatinine ≤ 1.5 X institutional upper limit of normal * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) * Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: * Patients with primary sites of the nasopharynx, salivary gland, or skin * Patients that have been previously treated with taxane chemotherapies * Patients that have previously received radiation to the site of planned surgery * History of allergic reactions attributed to compounds of similar chemical or biologic composition to FID-007 or other agents used in study * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants * Any diagnosis of immunodeficiency or patients receiving immunosuppressive therapy within 14 days of enrollment. Prednisone dose of ≤ 10mg is allowed

Outcomes

Primary Outcomes

Evaluate the phenotypical and functional changes of different T cell subsets within the tumor microenvironment after treatment with FID-007

Assessment of gene expression changes before and after the treatment with FID-007 by using paired biopsy samples by single cell-ribonucleic acid sequencing techniques. More specifically, the interested genes can be grouped as these four categories: (1) key immune checkpoint genes, including PD1, CTLA4, TIM3, LAG3, TIGIT, BTLA, VISTA, CD160, IDO, SIGLEC-15; (2) Gene signatures associated with T cell exhaustion: TOX, Blimp-1, Eomes, CD38, GZMB, GZMZ; (3) Gene signatures associated with T cell activation: CD3, CD28, NFAT, ZAP-70, CCR5, CCR7, and CXCR3, TCF-1; and (4) Gene signatures associated with T cell memory: CD45RO, CD62L, CCR7, IL-7R, BCL6, CD44, CXCR3.

Time frame: Baseline up to 30 days

Secondary Outcomes

Incidence of adverse events (AEs)

A summary table at subject level focusing on grade 3 or higher treatment related AEs (as per Common Terminology Criteria for Adverse Events version 5.0) will be provided.

Time frame: Baseline up to 30 days

Major pathologic response rate

Major pathologic response defined as 1-10% viable tumor on surgical specimen. Will be calculated based on the proportions that we calculated in the patient samples and their two-sided 95% confidence interval will also be estimated using Exact Clopper-Pearson method.

Time frame: Up to 30 days

Complete pathologic response rate

Complete pathologic response is defined as 0% viable tumor. Will be calculated based on the proportions that we calculated in the patient samples and their two-sided 95% confidence interval will also be estimated using Exact Clopper-Pearson method.

Time frame: Up to 30 days

Rate of locoregional recurrence

Percentage of patients who develop local-regional recurrence (identification of disease growth) in the primary site or regional lymphatics based on imaging and/or clinical exam.

Time frame: Within 2 years of surgery (surgery will occur approximately 3-6 weeks after last dose of FID-007)

Rate of distant metastasis

The percentage of patients who develop distant metastasis within 2 years of surgery. Distant disease is cancer that is found in another part of the body that is far away from where the original (primary) tumor first formed.