ACR-368 + Gemcitabine for Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Christine Chung, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Disqualifiers: Brain metastases, Cardiovascular disease, Pregnancy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you should not have had any prior systemic therapy for 4 weeks before starting the study treatment.

What data supports the idea that ACR-368 + Gemcitabine for Head and Neck Cancer is an effective drug?

The available research shows that Gemcitabine, when tested alone, did not show significant effectiveness in treating head and neck cancer, as there were no objective treatment responses and the median survival was only 6 months. However, in preclinical studies, Gemcitabine showed a significant antitumor effect in human tumor models, performing better than other drugs like cisplatin and methotrexate. This suggests potential when combined with other treatments, but specific data on ACR-368 + Gemcitabine for head and neck cancer is not provided in the available research. ^{1 2 3 4 5}

What safety data is available for ACR-368 and Gemcitabine in head and neck cancer treatment?

The safety data for Gemcitabine (Gemzar) in head and neck cancer treatment includes findings from a phase II trial where 26 patients experienced nausea and vomiting, with infrequent grade 3 or 4 hematologic toxicities. Two patients developed neutropenic infections, and one patient had fatal liver failure, possibly due to liver metastases or infection. Gemcitabine was not considered active enough as monotherapy for further evaluation in this disease population. Additionally, Gemcitabine has been studied in combination with cisplatin, showing promising overall survival rates in recurrent/metastatic squamous cell carcinoma of the head and neck. However, specific safety data for ACR-368 (Prexasertib, LY-2606368) in combination with Gemcitabine for head and neck cancer is not detailed in the provided research. ^{1 2 4 5 6}

Is the drug ACR-368, Gemcitabine a promising treatment for head and neck cancer?

Yes, Gemcitabine shows promise as a treatment for head and neck cancer. It has demonstrated significant antitumor effects in preclinical studies and has been effective when combined with other treatments like radiotherapy. It also has a broad anti-tumor effect and a favorable safety profile, making it a good candidate for further clinical trials. ^{1 2 7 8 9}

Research Team

Christine Chung, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for individuals with recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC). Participants should not have had previous chemotherapy for their recurrent/metastatic disease, must be able to receive medication intravenously, and have measurable disease as per RECIST criteria. Key exclusions include prior treatment with ACR-368 or gemcitabine in the metastatic setting, active infections, significant cardiovascular disease, or other serious medical conditions.

Inclusion Criteria

* 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.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ACR-368 and low dose gemcitabine every 2 weeks in 4-week cycles

Up to 24 months

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ACR-368 (Anti-cancer agent)
• Gemcitabine (Anti-metabolites)

Trial Overview The study is testing the effectiveness and safety of a combination therapy: ACR-368 (prexasertib) alongside low dose gemcitabine. Patients will be treated every two weeks over four-week cycles. The goal is to see how well this combo works against HNSCC compared to standard treatments.

Participant Groups

Group I: Cohort B (p16/HPV-pos) Experimental Treatment 2 Interventions

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.

Group II: Cohort A (p16/HPV-neg) Experimental Treatment 2 Interventions

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Moffitt Cancer Center Tampa, FL

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Patients Recruited

145,000+

Acrivon Therapeutics

Industry Sponsor

Trials

3

Patients Recruited

520+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of gemcitabine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Southwest Oncology Group phase II study. Samlowski, WE., Gundacker, H., Kuebler, JP., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical in vivo activity of 2',2'-difluorodeoxycytidine (Gemcitabine) against human head and neck cancer. Braakhuis, BJ., van Dongen, GA., Vermorken, JB., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and vinorelbine in recurrent head and neck cancer: pharmacokinetic and clinical results. Airoldi, M., Cattel, L., Cortesina, G., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and feasibility of Apatinib and S-1 as a novel oral induction therapy in locally advanced head and neck squamous cell carcinoma: an exploratory phase 2 open-label, single-arm trial. Jiang, W., Li, R., Zhang, L., et al.[2023]

In a study of 40 male patients with recurrent/metastatic squamous cell carcinoma of the head and neck, the combination of gemcitabine and cisplatin showed a 30% overall response rate and a 53.3% disease control rate, indicating its efficacy as a first-line treatment.

The treatment was associated with significant side effects, including severe leukopenia in 65% of patients and anemia in 27.5%, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promising overall survival of patients with recurrent/metastatic squamous cell carcinoma of head and neck receiving gemcitabine plus cisplatin treatment: report of a multi-center phase II study. Yang, MH., Chang, PM., Tzeng, CH., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open label, single-arm, phase Ib clinical trial. Huang, X., Liu, Q., Zhong, G., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine-based induction chemotherapy and concurrent with radiation in advanced head and neck cancer. El Deen, DA., Toson, EA., El Morsy, SM.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of advanced head and neck cancer. Raguse, JD., Gath, HJ., Bier, J., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II feasibility study of concurrent radiotherapy and gemcitabine in chemonaive patients with squamous cell carcinoma of the head and neck: long-term follow up data. Specenier, PM., Van den Weyngaert, D., Van Laer, C., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of gemcitabine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Southwest Oncology Group phase II study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Preclinical in vivo activity of 2',2'-difluorodeoxycytidine (Gemcitabine) against human head and neck cancer. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Gemcitabine and vinorelbine in recurrent head and neck cancer: pharmacokinetic and clinical results. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and feasibility of Apatinib and S-1 as a novel oral induction therapy in locally advanced head and neck squamous cell carcinoma: an exploratory phase 2 open-label, single-arm trial. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Promising overall survival of patients with recurrent/metastatic squamous cell carcinoma of head and neck receiving gemcitabine plus cisplatin treatment: report of a multi-center phase II study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open label, single-arm, phase Ib clinical trial. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine-based induction chemotherapy and concurrent with radiation in advanced head and neck cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of advanced head and neck cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Phase II feasibility study of concurrent radiotherapy and gemcitabine in chemonaive patients with squamous cell carcinoma of the head and neck: long-term follow up data. [2022]