Squamous Cell Carcinoma of Head and Neck
Conditions
Brief summary
To learn if TTI-101 can reduce the growth of HPV-negative squamous cell carcinomas of the head and neck when given before standard of care surgery.
Detailed description
Objectives: Primary: • To determine the change in pY-STAT3 H-score in tumor tissue in post-treatment resection specimens versus pre-treatment biopsy specimens. Secondary: * To determine the safety and tolerability of pre-surgery TTI-101 in patients with Stage II-IV HPV-negative HNSCC who are planned for definitive local surgery with or without radiation. * To determine the individual pre/post treatment changes in pY-STAT3 H-scores in epithelial and stromal tumor cells. * To determine the pathologic response rate to pre-surgery TTI-101. * To determine the overall response rate (ORR) to pre-surgery TTI-101 using RECIST v1.1 criteria. * To determine the disease free, disease specific and overall survival (DFS, DSS, OS) after pre-surgery TTI-101 treatment and SOC surgery. Exploratory: * To evaluate the effects of pre-surgery TTI-101 on circulating and tumor-infiltrating immunocytes, and on the intratumoral expression of PD-1 along with other immune related molecules. * To compare outcome measures (response rate and survival) in control versus TTI-101-treated patients. * To determine the association of immunologic changes with treatment response. * To determine the association of pharmacokinetic (PK) measures with treatment response.
Interventions
DRUGControl Group
Given by PO
DRUGTTI-101
Given by PO
Sponsors
Tvardi Therapeutics, Inc
National Institutes of Health (NIH)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must meet the following criteria for study entry: * Biopsy-proven primary Stage II-IV squamous cell carcinoma of the head and neck * For oropharyngeal cancer patients: HPV-negative by p16 and/or direct high-risk HPV assessment * Surgical resection must be planned as primary therapy with or without adjuvant radiation therapy. * Signed Informed Consent Form (ICF). * Ability and willingness to comply with the requirements of the study protocol. * Ability to swallow study drug. * Age years of 18 years. * Measurable disease per RECIST v1.1 (see Appendix 2) and/or per direct clinical measurements. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (see Appendix 4) * Adequate hematologic and hepatorenal function, defined by the following laboratory results obtained within 4 weeks prior to study entry: * ANC 1500 cells/L * Platelet count 100,000/L; * Hemoglobin 9.0 g/dL * Total bilirubin 1.5 upper limit of normal (ULN) with the following exception: Patients with known Gilbert disease who have serum bilirubin level 3 ULN may be enrolled. * AST and ALT 2.5 ULN * Alkaline phosphatase 2.5 ULN * Serum creatinine clearance ≥60 mL/min, measured or calculated per institutional standard protocol • INR and aPTT 1.5 ULN * This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose. * No evidence of distant metastases. * A male participant must agree to use contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR * A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 90 days after the last dose of study treatment.
Exclusion criteria
Patients who meet any of the following criteria will be excluded from study entry. General
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | through study completion; an average of 1 year. |
Outcome results
None listed