Head and Neck Squamous Cell CarcinomaPhase 2NCT06597565
A Phase II Study of ACR-368 and Low Dose Gemcitabine in R/M HNSCC
A Phase 2 study testing Gemcitabine and ACR-368 in people with Head and Neck Squamous Cell Carcinoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of the study is to determine the activity and safety of ACR-368 (prexasertib) in combination with gemcitabine in participants with Head and Neck Squamous Cell Carcinoma (HNSCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Gemcitabine and ACR-368
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Sep 2024to 23 Aug 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Patient (or a legally authorized representative) must understand and voluntarily sign informed consent prior to any study-related assessments/procedures being conducted.
- Must be able and willing to comply with the study visit schedule and protocol requirements.
- Must have sufficient archived tumor tissue available for p16 immunohistochemistry (IHC) staining if the status is unknown. HPV status determined by HPV DNA sequencing, HPV DNA/RNA in situ hybridization, or equivalent assays using tumor tissue or cell free HPV DNA testing or equivalent using blood-based assays are also acceptable. If there is a discrepancy between p16 IHC and HPV detection assay results, HPV detection assay result will be used.
- Must have sufficient archived tumor tissue available for OncoSignature determination. The tumor tissue must be less than 3 months old from the enrollment date. There should not be any intervening systemic therapy from the date of tumor tissue collection. If not, patient must agree to a fresh tumor biopsy before starting the treatments.
- Must agree to a biopsy after the lead-in LDG infusion and at the time of disease progression (or end of treatment if applicable).
- Must have R/M HNSCC including oral cavity, oropharynx, larynx, and hypopharynx. Patients with p16-positive or HPV-positive unknown primary of head and neck are eligible.
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- Must have been treated with one prior line of PD-1/PD-L1 inhibitor with/without chemotherapy. Patients who are immunotherapy ineligible due to history of autoimmune disease or steroid requirement (prednisone >10mg per day or equivalent) are allowed to enroll without the one prior line of PD-1/PD-L1 inhibitor with/without chemotherapy. There is no limitation on the number of prior therapies received in the R/M setting.
- Must have at least one measurable lesion as defined by RECIST v1.1.
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Must meet the laboratory criteria outlined in the protocol. Blood transfusion and/or blood product support are allowed.
- Patients of childbearing potential and patients whose sexual partners are of childbearing potential must be willing to practice an approved method of highly effective birth control with their partners starting at the time of informed consent and for 1 year after the completion of the study treatment regimen.
Who cannot join
- Patients should not have any prior systemic therapy for 4 weeks from the time of the study treatment.
- Patients should not have any palliative radiation therapy for 2 weeks from the time of the study treatment. Palliative radiation therapy is permitted during the study treatment if it does not involve target lesions.
- Patients with prior therapy-related toxicities Grade >1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0; except for dysphagia, alopecia, or vitiligo. Immunotherapy-related endocrinopathies stable for at least 1 month, and controlled with hormonal replacement, are not excluded. Grade 2 neuropathy stable for at least 2 weeks and controlled with supportive care medications are not excluded.
- Patients with symptomatic and/or untreated brain metastases (of any size and any number). Patients with definitively treated brain metastases may be eligible, must be stable for at least 2 weeks and must be asymptomatic with or without prednisone <10mg (or equivalent).
- Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association (NYHA) Class 2 or higher.
- Patients with cardiovascular disease defined as: A) Uncontrolled hypertension defined as blood pressure > 160/90 mmHg at Screening confirmed by repeat (medication permitted). B) History of torsades de pointes, significant Screening electrocardiogram (ECG) abnormalities, including ventricular rhythm disturbances, unstable cardiac arrhythmia requiring medication, pathologic symptomatic bradycardia, left bundle branch block, second degree atrioventricular (AV) block type II, third degree AV block, Grade ≥ 2 bradycardia, uncorrected hypokalemia not amenable to correction, congenital long QT syndrome, prolonged QT interval due to medications, corrected QT (QTc) > 450 msec (for men) or > 470 msec (for women). C) Symptomatic heart failure (per New York Heart Association guidelines; (Caraballo, 2019), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction < 20%, transient ischemic attack, or cerebrovascular accident within 6 months of Day 1).
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- Patients who have had another primary malignancy within the previous 3 years (except for those who do not require treatment or have been curatively treated >1 year ago, and in the judgment of the Investigator, do not pose a significant risk of recurrence; including, but not limited to, non-melanoma skin cancer, ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS], or prostate cancer Gleason score ≤6.).
- Patients who are of the following protected classes will be excluded: Pregnant, parturient, or breastfeeding women. Persons who are hospitalized without consent or those deprived of liberty because of a judiciary or administrative decision. Patients with a legal protection measure or a person who cannot express his/her consent and for whom a legally authorized representative is not available.
- Patients in emergency situations who cannot consent to the study and for whom a legally authorized representative is not available.
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
Moffitt Cancer Center
Tampa, Florida, 33612
Kara Hoffman, 813-745-6020, kara.hoffman@moffitt.org
Christine Chung, MD
About this study
Official title: A Phase II Study of ACR-368 and Low Dose Gemcitabine Combination Therapy in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
The purpose of the study is to determine the activity and safety of ACR-368 (prexasertib) in combination with gemcitabine in participants with Head and Neck Squamous Cell Carcinoma (HNSCC). Participants will receive the study drugs ACR-368 and a low dose of gemcitabine once every 2 weeks in 4-week cycles and will continue on treatment unless the disease deteriorates.
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- Gemcitabine, ACR-368
- 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.
GemcitabineDrug
Gemcitabine is a standard of care given at ultralow dose in combination with the experimental drug ACR-368.
ACR-368Drug
Also called Prexasertib
ACR-368 is an experimental drug.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (p16/HPV-neg) | Experimental | Participants with p16/HPV-negative recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) will be assigned to Cohort A. Participants will be administered lead-in low dose gemcitabine (LDG) 10 mg/m2 IV Day -7 (+/- 3 days, before Cycle 1 only) followed by ACR-368 105 mg/m2 IV every 2 weeks and LDG 10 mg/m2 every 2 weeks until discontinuation due to disease progression, intolerability, or consent withdrawal. When delay or discontinuation of the treatment is necessary, both ACR-368 and LDG will be delayed or discontinued together. Receives: Drug: Gemcitabine; Drug: ACR-368 |
| Cohort B (p16/HPV-pos) | Experimental | Participants with p16/HPV-positive R/M HNSCC will be assigned to Cohort B. Participants will be administered lead-in low dose gemcitabine (LDG) 10 mg/m2 IV Day -7 (+/- 3 days, before Cycle 1 only) followed by ACR-368 105 mg/m2 IV every 2 weeks and LDG 10 mg/m2 every 2 weeks until discontinuation due to disease progression, intolerability, or consent withdrawal. When delay or discontinuation of the treatment is necessary, both ACR-368 and LDG will be delayed or discontinued together. Receives: Drug: Gemcitabine; Drug: ACR-368 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate: Cohort A
The overall response rate will be determined by investigator review (IR) and blinded independent central review (BICR).
Measured: Up to 24 Months
Overall Response Rate: Cohort B
The overall response rate will be determined by investigator review (IR) and blinded independent central review (BICR).
Measured: Up to 24 Months
Secondary outcomes (4)
Safety and Tolerability
The number of patients who experience an AE or SAE.
Measured: Up to 24 Months
Duration of response (DOR)
DOR will be analyzed using the Kaplan-Meier method.
Measured: Up to 24 Months
Progression Free Survival (PFS)
PFS will be analyzed using the Kaplan-Meier method.
Measured: Up to 24 Months
Overall Survival (OS)
OS will be analyzed using the Kaplan-Meier method.
Measured: Up to 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start25 Sep 2024
- Primary completion23 Aug 2028 (estimated)
- Study completion23 Aug 2028 (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 Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Acrivon Therapeutics
- Responsible party
- Sponsor
- Investigators
- Christine Chung, MD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06597565
- Sponsor's protocol ID
- MCC-22485
- Status last verified
- Oct 2025
- First submitted
- 12 Sep 2024
- Last updated
- 20 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of ACR-368 and Low Dose Gemcitabine Combination Therapy in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT06597565
- Acronym / sponsor ID
- MCC-22485
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 43 participants (estimated)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Acrivon Therapeutics
- Study start
- 25 Sep 2024 (actual)
- Primary completion
- 23 Aug 2028 (estimated)
- Study completion
- 23 Aug 2028 (estimated)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to determine the activity and safety of ACR-368 (prexasertib) in combination with gemcitabine in participants with Head and Neck Squamous Cell Carcinoma (HNSCC). Participants will receive the study drugs ACR-368 and a low dose of gemcitabine once every 2 weeks in 4-week cycles and will continue on treatment unless the disease deteriorates.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A (p16/HPV-neg) | Experimental | Drug: Gemcitabine, Drug: ACR-368Participants with p16/HPV-negative recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) will be assigned to Cohort A. Participants will be administered lead-in low dose gemcitabine (LDG) 10 mg/m2 IV Day -7 (+/- 3 days, before Cycle 1 only) followed by ACR-368 105 mg/m2 IV every 2 weeks and LDG 10 mg/m2 every 2 weeks until discontinuation due to disease progression, intolerability, or consent withdrawal. When delay or discontinuation of the treatment is necessary, both ACR-368 and LDG will be delayed or discontinued together. |
| Cohort B (p16/HPV-pos) | Experimental | Drug: Gemcitabine, Drug: ACR-368Participants with p16/HPV-positive R/M HNSCC will be assigned to Cohort B. Participants will be administered lead-in low dose gemcitabine (LDG) 10 mg/m2 IV Day -7 (+/- 3 days, before Cycle 1 only) followed by ACR-368 105 mg/m2 IV every 2 weeks and LDG 10 mg/m2 every 2 weeks until discontinuation due to disease progression, intolerability, or consent withdrawal. When delay or discontinuation of the treatment is necessary, both ACR-368 and LDG will be delayed or discontinued together. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patient (or a legally authorized representative) must understand and voluntarily sign informed consent prior to any study-related assessments/procedures being conducted.
- Must be able and willing to comply with the study visit schedule and protocol requirements.
- Must have sufficient archived tumor tissue available for p16 immunohistochemistry (IHC) staining if the status is unknown. HPV status determined by HPV DNA sequencing, HPV DNA/RNA in situ hybridization, or equivalent assays using tumor tissue or cell free HPV DNA testing or equivalent using blood-based assays are also acceptable. If there is a discrepancy between p16 IHC and HPV detection assay results, HPV detection assay result will be used.
- Must have sufficient archived tumor tissue available for OncoSignature determination. The tumor tissue must be less than 3 months old from the enrollment date. There should not be any intervening systemic therapy from the date of tumor tissue collection. If not, patient must agree to a fresh tumor biopsy before starting the treatments.
- Must agree to a biopsy after the lead-in LDG infusion and at the time of disease progression (or end of treatment if applicable).
Key exclusion criteria (9 listed)
- Patients should not have any prior systemic therapy for 4 weeks from the time of the study treatment.
- Patients should not have any palliative radiation therapy for 2 weeks from the time of the study treatment. Palliative radiation therapy is permitted during the study treatment if it does not involve target lesions.
- Patients with prior therapy-related toxicities Grade >1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0; except for dysphagia, alopecia, or vitiligo. Immunotherapy-related endocrinopathies stable for at least 1 month, and controlled with hormonal replacement, are not excluded. Grade 2 neuropathy stable for at least 2 weeks and controlled with supportive care medications are not excluded.
- Patients with symptomatic and/or untreated brain metastases (of any size and any number). Patients with definitively treated brain metastases may be eligible, must be stable for at least 2 weeks and must be asymptomatic with or without prednisone <10mg (or equivalent).
- Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association (NYHA) Class 2 or higher.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GemcitabineGemcitabine is a standard of care given at ultralow dose in combination with the experimental drug ACR-368. | Drug | Cohort A (p16/HPV-neg), Cohort B (p16/HPV-pos) |
| ACR-368Also: PrexasertibACR-368 is an experimental drug. | Drug | Cohort A (p16/HPV-neg), Cohort B (p16/HPV-pos) |
Primary outcome
Overall Response Rate: Cohort A
Time frame: Up to 24 Months
The overall response rate will be determined by investigator review (IR) and blinded independent central review (BICR).
Overall Response Rate: Cohort B
Time frame: Up to 24 Months
The overall response rate will be determined by investigator review (IR) and blinded independent central review (BICR).
4 secondary outcomes
Safety and Tolerability
Time frame: Up to 24 Months
Duration of response (DOR)
Time frame: Up to 24 Months
Progression Free Survival (PFS)
Time frame: Up to 24 Months
Overall Survival (OS)
Time frame: Up to 24 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christine Chung, MD principal investigator
Moffitt Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gemcitabine and ACR-368 in people with Head and Neck Squamous Cell Carcinoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
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 11 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 20 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kara Hoffman (813-745-6020, kara.hoffman@moffitt.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate: Cohort A (time frame: Up to 24 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Oct 2025.