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Squamous Cell Carcinoma of Head and NeckEarly Phase 1NCT05845307

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

A Early Phase 1 study testing TTI-101 in people with Squamous Cell Carcinoma of Head and Neck, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Squamous Cell Carcinoma of Head and Neck
What is being tested?
TTI-101
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
20 Jun 2025to 13 Nov 2025
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • Patients who meet any of the following criteria will be excluded from study entry.
  • General Exclusion Criteria:
  • 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
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  • 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.
  • Uncontrolled hypertension (>160/100mm Hg).
  • History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemicalor biologic composition as TTI-101 (hydroxyl-naphthalene sulfonamides).
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Previous treatment of the current malignancy with a STAT inhibitor.
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Medication-Related Exclusion Criteria:
  • Bisphosphonate therapy for symptomatic hypercalcemia
  • Use of bisphosphonate therapy for other reasons (e.g., osteoporosis) is allowed.
  • Received oral or IV antibiotics within 2 weeks prior to treatment
  • Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
  • Treatment with an investigational agent (not standard of care) within 3 weeks prior to treatment (or within five halflives of the investigational product, whichever is longer)
  • Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to treatment
  • Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
  • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.

About this study

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.

Read the 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.
Being tested
Control Group, TTI-101
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Control GroupDrug

    Given by PO

  • TTI-101Drug

    Given by PO

Study groups in NCT05845307
Study groupRoleWhat they receive
Control GroupExperimentalParticipants you will be randomly assigned to either receive the study drug or be in a control group.
Receives: Drug: Control Group
TTI-101ExperimentalParticipants you will be randomly assigned to either receive the study drug or be in a control group.
Receives: Drug: TTI-101

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

    Measured: through study completion; an average of 1 year.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 May 2023
  2. Study start20 Jun 2025
  3. Primary completion13 Nov 2025
  4. Study completion13 Nov 2025

Why it stopped: 0 participants

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05845307
Sponsor's protocol ID
2022-0001
Other IDs
NCI-2023-03573
Status last verified
Nov 2025
First submitted
25 Apr 2023
Last updated
8 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing TTI-101 in people with Squamous Cell Carcinoma of Head and Neck, run by M.D. Anderson Cancer Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; an average of 1 year.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05845307.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2025.

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