Randomized Pre-surgical Window-of-Opportunity Trial of TTI-101 in Patients With Stage II-IV Resectable HPV-negative Squamous Cell Carcinoma of the Head and Neck

NCT05845307 | Withdrawn Early Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0001NCI-2023-03573
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Squamous Cell Carcinoma of Head and Neck

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (2)

Control Group

EXPERIMENTAL

Participants you will be randomly assigned to either receive the study drug or be in a control group.

Drug: Control Group

TTI-101

EXPERIMENTAL

Participants you will be randomly assigned to either receive the study drug or be in a control group.

Drug: TTI-101

Interventions

Control Group DRUG

Given by PO

Control Group

TTI-101 DRUG

Given by PO

TTI-101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry.
• Any prior systemic or radiotherapy within the last 4 months directed towards the squamous cell carcinoma of the head and neck that is to be resected as part of SOC therapy.
• Standard of care anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, for concurrent malignancy or unresected squamous cell carcinoma of the head and neck within 3 weeks prior to initiation of study treatment.
• AEs from prior anticancer therapy that have not resolved to Grade 1 except for alopecia, Grade 2 neuropathy or endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement are eligible
• Pregnancy, lactation, or breastfeeding
• Inability to comply with study and follow-up procedures
• Has a known active Hepatitis B (defined as Hepatitis B RNA detected) or known active Hepatitis C virus (defined as HCV RNA is detected) infection, or known active HIV (defined as HIV RNA is detected) infection.
• Active tuberculosis
• Severe infections within 4 weeks prior to treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Signs or symptoms of infection as determined by the treating team within 2 weeks prior to treatment
• Major surgical procedure within 28 days prior to treatment
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed or mRNA vaccines is allowed.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, well-differentiated thyroid cancer, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
• History of significantly impaired cardiac function such as unstable angina pectoris, congestive heart failure with New York Heart Association (NYHA) class III or IV, myocardial infarction within the last 12 months prior to trial entry; signs of pericardial effusion, serious arrhythmia (including QTc prolongation of \>470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome or left ventricular ejection fraction \<50% on echocardiogram.
• History of cerebral vascular accident or stroke within the previous 2 years.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Tvardi Therapeutics, Inc: collaborator
• National Institutes of Health (NIH): collaborator

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Control Groups; C188-9 compound

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Andrew Sikora, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2023
• First Posted: May 6, 2023
• Study Start: June 20, 2025
• Primary Completion: November 13, 2025
• Study Completion: November 13, 2025
• Last Updated: December 8, 2025

Record last verified: 2025-11