FID-007 + Cetuximab for Head and Neck Cancer

(HNSCC Trial)

Recruiting at 6 trial locations

Overseen By Chief Scientific Officer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fulgent Pharma LLC.

Must not be taking: CYP2C8 inhibitors, CYP3A4 inhibitors

Disqualifiers: EBV-positive cancer, Uncontrolled HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: Through study completion, an average of 1 year

46 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 21 days or 5 half-lives for prior treatments like chemotherapy, radiotherapy, or immunotherapy before starting the study drug. Additionally, you cannot use certain medications that affect liver enzymes (CYP2C8 and CYP3A4) within 14 days before starting the study drug.

What data supports the effectiveness of the drug FID-007 + Cetuximab for head and neck cancer?

Research shows that cetuximab, when combined with paclitaxel, has been effective in treating head and neck cancer, improving survival rates and disease control. Cetuximab is known to enhance the effects of other cancer treatments by targeting specific cancer cell receptors, which may suggest potential benefits when used with FID-007. ^{1 2 3 4 5}

Is the combination of FID-007 and Cetuximab safe for humans?

Cetuximab has been generally well tolerated in various studies, with adverse events reported in some patients. Paclitaxel, a component of FID-007, has been studied in combination with other drugs and has shown a range of side effects, but specific safety data for FID-007 itself is not available in the provided research. ^{1 5 6 7 8}

What makes the drug FID-007 + Cetuximab unique for head and neck cancer?

FID-007 is unique because it involves paclitaxel encapsulated in a special polymer (PEOX), which may enhance its delivery and effectiveness, combined with cetuximab, a drug that targets cancer cell growth by blocking a specific receptor (EGFR). This combination aims to improve treatment outcomes by using a novel delivery method for paclitaxel alongside cetuximab's targeted action. ^{1 2 4 8 9}

What is the purpose of this trial?

The goal of this FID-007 Clinical Trial is to compare the efficacy of different dosing regimens of FID-007 in combination with Cetuximab in patients with recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC). The main questions it aims to answer are: to evaluate the efficacy, and to characterize the safety and tolerability. Eligible participants will be enrolled and randomized to 1 of 2 arms of FID-007 with fixed-dose Cetuximab in each 28-day cycle.

Research Team

Fulgent Clinical Sites

Principal Investigator

Fulgent Pharma LLC.

Eligibility Criteria

This trial is for adults over 18 with advanced head and neck squamous cell carcinoma that has grown despite previous treatment. Participants must have measurable disease, not be positive for Epstein-Barr virus in the nasopharynx, and be able to give informed consent.

Inclusion Criteria

Estimated life expectancy of at least 3 months

I have recovered from the side effects of my previous cancer treatments.

Measurable disease according to RECIST version 1.1

Exclusion Criteria

Known hypersensitivity to paclitaxel

I have HIV that is not well-controlled.

I am not taking any drugs that affect CYP2C8 or CYP3A4 enzymes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FID-007 in combination with Cetuximab. FID-007 is administered via IV infusion on Days 1, 8, and 15 of each 28-day cycle, and Cetuximab is administered on Days 1 and 15 starting from Cycle 2.

Through study completion, an average of 1 year

Visits every 2 weeks for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of overall survival, progression-free survival, and adverse events.

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if they meet certain criteria.

Long-term

Treatment Details

Interventions

• FID-007

Trial Overview The study tests different doses of FID-007 combined with a fixed dose of Cetuximab. Patients are randomly assigned to one of two groups to receive this combination therapy in repeated 28-day cycles, aiming to evaluate its effectiveness and safety.

Participant Groups

Group I: Arm A Active Control 1 Intervention

FID-007 (75 mg/m2) plus Cetuximab (500 mg/m2)

Group II: Arm B Active Control 1 Intervention

FID-007 (125 mg/m2) plus Cetuximab (500 mg/m2)

Who Is Running the Clinical Trial?

Fulgent Pharma LLC.

Lead Sponsor

Trials

2

Recruited

70+

Findings from Research

In a study of 46 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of weekly paclitaxel and cetuximab showed a promising overall response rate of 54%, with 22% achieving complete responses.

The treatment was well tolerated, with a disease control rate of 80% and median overall survival of 8.1 months, making it a potential option for patients who cannot receive platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Hitt, R., Irigoyen, A., Cortes-Funes, H., et al.[2022]

In a study of 37 patients with advanced squamous cell head and neck cancer, the addition of cetuximab to a treatment regimen of paclitaxel, carboplatin, and radiation resulted in a 3-year overall survival rate of 57%, which is similar to previous studies without cetuximab.

Despite the addition of cetuximab, improvements in locoregional control were not observed, indicating that further strategies are needed to enhance treatment effectiveness in preventing cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a survival analysis of a Brown University Oncology Group phase II study. Birnbaum, A., Dipetrillo, T., Rathore, R., et al.[2015]

In a study involving 300 patients with recurrent or metastatic head and neck squamous cell carcinoma, the combination of cetuximab and cisplatin was found to be equally effective as adding paclitaxel, with median progression-free survival of 5 months for the two-drug regimen and 8 months for the three-drug regimen, but no significant difference in overall survival or objective response rates.

The results suggest that the simpler two-drug regimen of cetuximab and cisplatin could be a viable first-line treatment option, as it did not compromise patient outcomes compared to the more complex three-drug combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Cetuximab Plus Cisplatin Alone or in Combination With Paclitaxel in Patients With Head and Neck Squamous Cell Carcinoma: A Randomized Trial. Zheng, Y., Dou, H., Li, Q., et al.[2023]

In a Phase III trial, adding cetuximab to radiotherapy for locoregionally advanced squamous cell carcinoma of the head and neck significantly improved median locoregional control from 14.9 to 24.4 months and overall survival from 29.3 to 49.0 months.

For patients with platinum-refractory recurrent or metastatic disease, cetuximab combined with platinum/5-fluorouracil showed improved survival, response rates (10-13%), and disease control (46-56%), along with better symptom management compared to platinum/5-fluorouracil alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of squamous cell carcinoma of the head and neck. Specenier, P., Vermorken, JB.[2019]

The TPEx regimen, which combines docetaxel, cisplatin, and cetuximab, achieved an objective response rate of 44.4% in 54 patients with recurrent or metastatic head and neck squamous cell carcinoma, indicating promising efficacy as a first-line treatment.

While the treatment was generally well-tolerated, notable adverse events included skin rash (16.6%) and non-febrile neutropenia (20.4%), with some serious complications leading to death, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Guigay, J., Fayette, J., Dillies, AF., et al.[2022]

The TIP regimen (taxol, ifosfamide, and cisplatin) demonstrated significant efficacy in treating recurrent or metastatic squamous cell carcinoma of the head and neck, achieving a 58% overall response rate and a 17% complete response rate among 52 patients.

The treatment was relatively well tolerated, with the most common severe side effect being transient neutropenia in 90% of patients, and no treatment-related deaths were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of paclitaxel, ifosfamide, and cisplatin in patients with recurrent head and neck squamous cell carcinoma. Shin, DM., Glisson, BS., Khuri, FR., et al.[2017]

The maximum tolerated dose (MTD) of paclitaxel given as a 96-hour continuous infusion during accelerated radiotherapy for advanced squamous cell carcinoma of the head and neck was determined to be 100 mg/m², with most patients completing the treatment without severe complications.

While some patients experienced significant side effects like Grade 4 mucositis and febrile neutropenia, all toxicities were reversible, and the treatment showed promising efficacy with complete responses in 8 out of 13 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of 96-hour paclitaxel infusion plus accelerated radiotherapy of unrespectable head and neck cancer. Machtay, M., Aviles, V., Kligerman, MM., et al.[2019]

Cetuximab, an anti-EGFR monoclonal antibody, effectively blocks receptor activation and enhances the effects of chemotherapy and radiotherapy in treating advanced solid tumors, as shown in preclinical studies and clinical trials involving 526 patients.

The drug has been generally well tolerated, with adverse events reported in 239 patients, and has shown promising clinical responses in patients who previously failed other treatments, leading to further phase II and III trials in head and neck and colorectal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EGFR as a target for anticancer therapy--focus on cetuximab. Baselga, J.[2022]

In a phase II trial involving 74 patients with advanced squamous cell carcinoma of the head and neck, the combination of cetuximab, cisplatin, and hyperfractionated accelerated radiotherapy resulted in a 2-year progression-free survival rate of 45% and a complete remission rate of 35%.

Despite the promising results, the study found significant toxicity, with severe side effects like mucositis and dysphagia occurring in over half of the patients, and a parallel study indicated that this enhanced therapy did not provide a survival advantage over standard chemoradiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperfractionated accelerated radiation therapy plus cetuximab plus cisplatin chemotherapy in locally advanced inoperable squamous cell carcinoma of the head and neck : Final 5‑year results of a phase II study. Kuhnt, T., Schreiber, A., Pirnasch, A., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. [2022]

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

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a survival analysis of a Brown University Oncology Group phase II study. [2015]

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

Efficacy and Safety of Cetuximab Plus Cisplatin Alone or in Combination With Paclitaxel in Patients With Head and Neck Squamous Cell Carcinoma: A Randomized Trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of squamous cell carcinoma of the head and neck. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. [2022]

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

Phase II trial of paclitaxel, ifosfamide, and cisplatin in patients with recurrent head and neck squamous cell carcinoma. [2017]

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

A phase I trial of 96-hour paclitaxel infusion plus accelerated radiotherapy of unrespectable head and neck cancer. [2019]

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

The EGFR as a target for anticancer therapy--focus on cetuximab. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Hyperfractionated accelerated radiation therapy plus cetuximab plus cisplatin chemotherapy in locally advanced inoperable squamous cell carcinoma of the head and neck : Final 5‑year results of a phase II study. [2018]