Head and Neck CancerPhase 1/2NCT07667400
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
A Phase 1/2 study testing SX-682 and DTX in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Head and neck cancers (HNCs) account for about 5% of all cancers worldwide. They grow in the mouth, throat, nasal cavity, or salivary glands. Prostate cancer is the most common cancer in men in the United States. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, Paranasal Sinus Neoplasms
- What is being tested?
- SX-682 and DTX
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2026to 1 Oct 2037
- Phase
- Phase 1/2
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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All Participants
- Age >= 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) <= 2
- Participants must have adequate organ and marrow function as defined below:
- ANC >= 1,500/mcL
- Hemoglobin (Hgb) >= 9 g/dL
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- Platelets (PLTs) >= 100,000/mcL
- Creatinine clearance >= 50 mL/min (by Cockroft-Gault formula)
- Total bilirubin <= 1.5 x iULN (<= 3 x ULN in participants with known/suspected Gilbert s disease)
- ALT/AST <= 2.5 x iULN
- Activated partial thromboplastin time (aPTT) <= 1.5 x iULN
- Contraception as follows:
- Women of child-bearing potential (WOCBP) must agree to use an effective method of contraception (barrier, hormonal, intrauterine device [IUD], surgical sterilization, abstinence) prior to study entry, for the duration of study treatment, and for up to 2 months after discontinuation of the study drugs. A participant may request a male partner to use an effective form of contraception to fulfill this requirement.
- Men able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to 4 months after discontinuation of the study drugs. A participant may request a female partner to use an effective form of contraception to fulfill this requirement. Men able to father a child must not freeze or donate sperm within the same period.
- Nursing participants must be willing to discontinue nursing from study treatment initiation through one week after the last dose of study drugs.
- Participants must be able to swallow oral medications.
- Human immunodeficiency virus (HIV)-infected participants must have undetectable viral load (VL) and be on effective anti-retroviral therapy within 4 weeks prior to the study treatment initiation and have no history of opportunistic infections or Castleman s disease within 12 months prior to the study treatment initiation.
- Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV VL.
- Participants with evidence of chronic hepatitis C virus (HCV) infection must have undetectable HCV VL.
- Participants must be able to understand and willing to sign a written informed consent document.
- Participants with HNC
- Histologically confirmed HNSCC (including oral cavity, oropharynx, larynx, hypopharynx, paranasal sinuses, nasopharynx) or SGC (including ACC and non-ACC) and recurrent/metastatic (R/M) or advanced incurable disease.
- Prior treatment as follows:
- Participants with R/M HNSCC must have prior systemic treatment (platinum-based chemotherapy and/or anti-PD(L)1 treatment).
- Participants with R/M SGC may have any number of prior systemic treatment lines; prior systemic treatment not required for participation.
- Participants must not have received systemic anticancer treatment within 3 weeks prior to first treatment administration. Note: Treatment-related toxicities must have resolved to Grade <2 or be minimal and not constitute a safety risk. Participants with SGC previously treated with hormonal therapies (e.g., drugs targeting the androgen receptor) may continue these drugs concomitantly with study therapy. Participants with bone metastases or hypercalcemia on intravenous bisphosphonate medications, denosumab, or similar agents, are eligible to participate and may continue this treatment.
- Presence of >= 1 measurable lesion by RECIST v 1.1 criteria.
- Participants with mCRPC
- Documented histopathological confirmation of prostate cancer. If no pathologic report or specimen is available, participants may enroll with a history of clinical course consistent with the disease.
- Participants must have mCRPC, defined as at least one lesion on TC-99 bone scan or at least one lesion that is measurable per RECIST 1.1.
- Participants must need ADT as part of their cancer therapy (unless previous orchiectomy)
- Castrate testosterone level (<50 ng/dl or 1.7 nmol/L)
- Prior treatment as follows:
- DTX for mCRPC is allowed but participants must not have had progression while on docetaxel or within 3 months after completing DTX for mCRPC
- Participants must have been previously treated with modern anti-androgens such as abiraterone, enzalutamide, apalutamide, or darolutamide.
- Progression defined as two consecutive rising PSA values at least 1 week apart or radiographic evidence of progression seen on computed tomography (CT) scan or TC- 99 bone scan.
- Toxicities related to prior therapy, including surgery and/or radiation, must have resolved to < Grade 1 per CTCAE v.6.0.
Who cannot join
- All participants
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to DTX, SX-682, or other agents used in study (e.g., polysorbate 80).
- Known active brain metastases. Note: Participants with previously treated brain metastases are eligible if imaging at least four weeks prior to first trial treatment shows no evidence of progression and neurologic symptoms have resolved, have no new or enlarging brain metastases, and are not using glucocorticoids for at least a week prior to first trial treatment
- Participants must not have received other investigational agents within 3 weeks prior to the first dose of the study drug(s).
- Participants must not have received major surgery within 14 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted). If participant underwent major surgery, they must have recovered adequately (according to the Principal Investigator) from the toxicity and/or complications from the intervention prior to starting study treatment.
- Treatment (systemic) with any medications or substances that are moderate or strong inducers or moderate or strong inhibitors of cytochrome P450 (CYP3A4) listed at https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions- table-substrates-inhibitors-and-inducers#table2-2,table3-3,table5-2 within 2 weeks or 5 half-lives (whichever is shorter) prior to the start of the study treatment.
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- Prior or concurrent malignancy whose natural history or treatment has potential to interfere with the safety or efficacy assessment of the study treatment.
- Participants with serious uncontrolled intercurrent illness evaluated by medical history, electrocardiogram (EKG), and physical exam that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study or that would limit compliance with study requirements.
- Participants with HNC
- Participants must not have received large-field radiotherapy within 2 weeks prior to first treatment administration. All residual treatment-related toxicities must have resolved to Grade <2 (except for radiation-induced xerostomia/dysgeusia) or be minimal and not constitute a safety risk.
- Positive pregnancy serum or urine beta-human chorionic gonadotropin (beta-hCG) test
- Participants with mCRPC
- Use of other medications for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g., phytoestrogens and saw palmetto) within 1 week prior to the study treatment initiation.
- Cancer related neuropathy at screening
- Baseline QTcF >= 470 ms
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
National Cancer Institute Referral Office, 888-624-1937, ncimo_referrals@mail.nih.gov
About this study
Official title: Phase I/II Trial of Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Background:
Head and neck cancers (HNCs) account for about 5% of all cancers worldwide. They grow in the mouth, throat, nasal cavity, or salivary glands. Prostate cancer is the most common cancer in men in the United States. Survival rates for these cancers are lower than 50% if they spread to other parts of the body or return after treatment. Better treatments are needed.
Read more
Objective:
To test a new drug (SX-682), combined with an approved drug (docetaxel, or DTX), in people with HNCs or prostate cancer.
Eligibility
People aged 18 years and older with an HNC or prostate cancer that has returned after treatment or has spread.
Design:
Participants will be screened. They will have blood tests, imaging scans, and a test of their heart function. A tissue sample (biopsy) of the tumor may be taken.
Participants will take the study drugs in 3-week cycles. SX-682 is a tablet taken by mouth twice a day from Days 1 to 11 of each cycle. Participants will get a supply of the drug to take home. DTX is given on Day 8 of each cycle through a tube attached to a needle inserted into a vein in the arm. Participants will come to the clinic on Days 1 and 8 of every cycle. They will take both drugs for up to 6 cycles.
Participants will have follow-up visits 1 week and 1 month after they finish taking the drugs. Follow-ups will continue every 3 months for 2 years. Then they will have phone or email check-ins twice a year until 5 years have passed.
Read the detailed description
Background
- Recurrent and advanced head and neck squamous cell cancers (HNSCC) are treated with systemic chemotherapy plus or minus checkpoint blockade and overall survival ranges between 6 to 15 months. Recurrent/metastatic salivary gland carcinomas (SGC) lack standardized treatment and respond poorly to checkpoint inhibitors. Therefore, both are clear unmet clinical needs.
- Docetaxel (DTX) has demonstrated activity in HNSCC and SGC. Preclinical data suggest that DTX increases both innate and adaptive immunity. Increased objective response rate from DTX was seen in patients with HNSCC previously exposed to checkpoint blockade compared to checkpoint-inhibitors na(SqrRoot) ve patients.
- Myeloid-derived suppressor cells (MDSCs) promote an immunosuppressive tumor microenvironment and treatment resistance in HNSCC. Preclinical models of head and neck cancers (HNC) show significant neutrophilic-MDSCs infiltrating the tumor, likely recruited through the CXCR1-2 pathway. MDSCs have been described also in some SGC subtypes, associated with lack of immune infiltration.
- In preclinical HNSCC models, blockade of CXCR1-2 chemokine receptors by dual allosteric inhibitor SX-682 has demonstrated a marked reduction in MDSCs trafficking to tumors resulting in increased immune effector cell infiltration. Further, SX-682 appears to downregulate tubulin-beta 3, which is reported to be responsible for DTX resistance.
- DTX is a standard option in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Despite improvements in survival with DTX, nearly all patients treated with DTX become refractory due to the development of resistance. Rationale combinations with DTX are needed to improve upon current treatments and overcome resistance mechanisms.
- In mCRPC, MDSCs remain a major mediator of immunosuppression in the tumor microenvironment. Targeting the CXCR1/2 pathway can be an alternate immunotherapeutic approach in treatment in an otherwise immunosuppressive tumor microenvironment.
- As in head and neck cancer (HNC), in prostate cancer models, SX-682 appears to downregulate tubulin-beta 3, which is reported to be responsible for DTX resistance.
- DTX in combination with SX-682 is a rational combinational approach for treating HNSCC, SGC, and mCRPC offering potential synergistic activity and the induction/restoration of chemotherapy-sensitivity and immune effector activity.
Objectives
- Phase I: To determine the recommended phase II dose (RP2D) of SX-682 in combination with DTX in participants with HNSCC, SGC, or mCRPC
- Phase II: To determine the efficacy of the combination of SX-682 and DTX in participants with HNSCC or SGC using objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST) v 1.1 or in participants with mCRPC using RECIST v1.1 and Prostate Cancer Working Group 3.
Eligibility
- Age >= 18 years
- Histologically confirmed HNSCC (including oral cavity, oropharynx, larynx, hypopharynx, paranasal sinuses, nasopharynx) or SGC (including adenoid cystic carcinoma [ACC] and non-ACC) and recurrent, metastatic (R/M) or advanced incurable disease or mCRPC
- Participants with HNSCC or SGC should have received at least 1 standard systemic therapy, or cannot tolerate standard therapy, or there is no standard therapy for their tumor type.
- Participants with mCRPC should have received modern anti-androgens.
Design
- This is a non-randomized, Phase I/II trial to determine the safety and efficacy of DTX in combination with SX-682 in participants with HNSCC, SGC, and mCRPC.
- In the Phase I portion of the study, participants will be enrolled in a 3+3 dose escalation schema using 4 SX-682 dose levels and a fixed dose of DTX (Arm 1).
- Following identification of RP2D for SX-682, an expansion phase (Phase II) will be initiated, using RP2D SX-682 with a fixed dose of DTX (Arm 2).
- DTX will be administered intravenously (IV) on day 8 of each 3-week cycle.
- SX-682 will be administered orally twice a day from day 1 to day 11 of each 3-week cycle.
- Participants will receive DTX and SX-682 for up to 6 cycles or until disease progression, intolerable side effects, the participant s request to discontinue therapy, or PI decision.
- Conditions
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, Paranasal Sinus Neoplasms, Nasopharyngeal Carcinoma, Oropharyngeal Squamous Cell Carcinoma, Hypopharyngeal Cancer
- Being tested
- SX-682, DTX
- Keywords
- Solid Tumors, Infusion, Chemotherapy, Carcinoma, Head and Neck, Prostate, molecule inhibitor
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Paranasal Sinus Neoplasms, Nasopharyngeal Carcinoma, Hypopharyngeal Neoplasms, Laryngeal Neoplasms, Salivary Gland Neoplasms, Carcinoma, Adenoid Cystic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SX-682Drug
SX-682 will be given orally (PO) twice a day at the dose of the corresponding dose level group (for Phase I) or at RP2D (for Phase II).
DTXDrug
DTX will be administered IV at 75 mg/m^2 over about 60 minutes
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Escalating doses of SX-682 + DTX Receives: Drug: SX-682; Drug: DTX |
| Arm 2 | Experimental | SX-682 at RP2D + DTX Receives: Drug: SX-682; Drug: DTX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: To determine the RP2D of SX-682 in combination with DTX in participants with HNSCC, SGC, or mCRPC
Toxicities will be tabulated and reported according to grade and type of toxicity experienced. Responses will be reported as the proportion of evaluable participants along with a confidence interval.
Measured: 28 days
Phase II: To determine the efficacy of the combination of SX-682 and DTX in participants with HNSCC or SGC using ORR per RECIST v 1.1 or with mCRPC using RECIST v1.1 and Prostate Cancer Working Group 3
Overall response rate (ORR) as defined by the proportion of participants who achieve a response (CR+PR) will be reported separately for each, along with 95% and 80% confidence intervals (Clopper-Pearson).
Measured: Assessment at baseline, C4D8, 7 days after C6, and then every 3 months until PD or until 2 years after study treatment initiation
Secondary outcomes (3)
To assess safety of SX-682 in combination with DTX
Toxicity will be reported descriptively for each cohort separately.
Measured: Assessed from the first study treatment, C1D1, through safety visit (28 days post-treatment) or start of new anticancer treatment, whichever comes first.
To assess progression free survival (PFS)
PFS will be determined separately by cohort using Kaplan-Meier plots. Medians and 95% confidence intervals will be provided for each of these secondary objectives. PFS will be determined separately for 6, 12 and 24 months.
Measured: Assessed at C1D1, C4D8, 7 days after C6, and then every 3 months until PD or until 2 years after study treatment initiation.
To assess overall survival (OS)
OS will be determined separately by cohort using Kaplan-Meier plots. Medians and 95% confidence intervals will be provided for each of these secondary objectives. OS will be determined separately for 2 and 5 years.
Measured: Assessed at C1-6D1, at the 28-day Safety visit; every 3 months until disease progression or 2 years after start of study treatment; every 6 months after disease progression until 5 years after start of study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2026
- Study start28 Oct 2026 (estimated)
- Primary completion1 Oct 2036 (estimated)
- Study completion1 Oct 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Charalampos Floudas, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07667400
- Sponsor's protocol ID
- 10002319
- Other IDs
- 002319-C
- Status last verified
- 13 Oct 2026
- First submitted
- 24 Jun 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.