Chemotherapy Combinations for Head and Neck Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Cetuximab, EGFR inhibitors

Disqualifiers: Metastases, Prior chemotherapy, Pregnancy, 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: 3

128 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to learn which chemotherapy combination is more effective in treating locally advanced head and neck squamous cell carcinoma. The side effects of these combinations will also be studied.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination for head and neck cancer?

Research shows that combinations of cisplatin or carboplatin with 5-fluorouracil and cetuximab are more effective than using cisplatin or carboplatin with 5-fluorouracil alone for treating head and neck cancer. Additionally, docetaxel and cisplatin are known to be active against this type of cancer, and cetuximab combined with these drugs has shown promising results. ^{1 2 3 4 5}

Is the chemotherapy combination for head and neck cancer safe for humans?

The chemotherapy combinations involving drugs like docetaxel, cisplatin, 5-fluorouracil, carboplatin, and cetuximab have been studied for head and neck cancer. While they can be effective, they may cause severe side effects such as neutropenia (a low level of white blood cells, which can increase infection risk). Safety varies, and some combinations are generally considered feasible, but side effects can limit treatment adherence. ^{1 2 3 4 6}

What makes this drug combination unique for head and neck cancer?

This drug combination is unique because it includes a mix of chemotherapy agents like docetaxel, cisplatin, and cetuximab, which have shown strong antitumor activity and radiopotentiating properties, potentially enhancing the effectiveness of radiotherapy. Additionally, using carboplatin instead of cisplatin may reduce toxicity, making the treatment more tolerable for patients. ^{1 2 4 7 8}

Research Team

Renata Ferrarotto, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with advanced head and neck squamous cell carcinoma, specifically stages IV T0-4 N2b-3 M0. Participants must have good performance status (ECOG PS 0-1), adequate organ function, and measurable disease by RECIST criteria. They cannot have had prior treatments targeting EGFR pathways or radiotherapy to the head and neck, other invasive cancers (with exceptions), or be pregnant/breastfeeding.

Inclusion Criteria

My liver functions are within normal limits, except for possible Gilbert's disease.

My kidneys are working well enough (creatinine clearance is at least 40 ml/min).

I have a confirmed diagnosis of squamous cell carcinoma in my throat or mouth.

Exclusion Criteria

I agree to use effective birth control during and for 3 months after treatment.

I need some help with my daily activities.

I have previously been treated with drugs targeting the EGFR pathway.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive induction chemotherapy with either PCC or C-TPF regimen

6-9 weeks

Weekly visits for drug administration and monitoring

Radiation Therapy

Participants receive radiation therapy, with or without chemotherapy, based on the treatment group

7 weeks

Daily visits Monday through Friday

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Clinic visits every 3 months

Treatment Details

Interventions

• Carboplatin
• Cetuximab
• Cisplatin
• Docetaxel
• Fluorouracil
• Paclitaxel

Trial Overview The trial is testing two chemotherapy combinations: Paclitaxel, Carboplatin, Cetuximab (PCC) versus Cetuximab with Docetaxel, Cisplatin and Fluorouracil (C-TPF). It aims to determine which regimen is more effective for treating locally advanced head and neck cancer.

Participant Groups

Group I: PCC Group + RT + Chemotherapy Experimental Treatment 5 Interventions

Group A: Paclitaxel, Carboplatin and Cetuximab (PCC) Induction + Radiation (RT) + Chemotherapy

Group II: PCC Group + RT Experimental Treatment 4 Interventions

Group A: Paclitaxel, Carboplatin and Cetuximab (PCC) Induction + Radiation (RT)

Group III: C-TPF Group + RT + Chemotherapy Experimental Treatment 6 Interventions

Group B: Cetuximab, Docetaxel, Cisplatin and Fluorouracil (C-TPF) Induction + Radiation (RT) + Chemotherapy

Group IV: C-TPF Group + RT Experimental Treatment 5 Interventions

Group B: Cetuximab, Docetaxel, Cisplatin and Fluorouracil (C-TPF) Induction + Radiation (RT)

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Findings from Research

The combination of carboplatin, oral tegafur, and cetuximab is a safe and well-tolerated first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), with a high compliance rate among patients.

In a study of 104 patients, the treatment resulted in a median overall survival of 11 months and a progression-free survival of 6 months, with an overall response rate of 35%, indicating its efficacy in managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous 5-Fluorouracil in Patients With Advanced Squamous Cell Carcinoma: A Retrospective Study. Buxó, E., Sosa, A., Reig, O., et al.[2019]

The new chemotherapy regimen combining docetaxel, cisplatin, and cetuximab (B-CRT) for treating locally advanced head and neck squamous cell carcinoma resulted in severe neutropenia in 56% of patients, indicating significant safety concerns.

Due to the high incidence of adverse events, particularly neutropenia and leukopenia, the study was terminated early, and it remains unclear if B-CRT is as effective as the standard TPF-CRT regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of concurrent bio-chemoradiotherapy using docetaxel, cisplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma. Nishimura, G., Taguchi, T., Takahashi, M., et al.[2018]

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 combination of docetaxel and cisplatin demonstrated a significant overall response rate of 53.7% in patients with locally advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, indicating its efficacy as a treatment option.

Despite common hematologic and non-hematologic toxicities, the treatment was generally well-tolerated, with serious adverse effects being infrequent due to the use of corticosteroid prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. Schöffski, P., Catimel, G., Planting, AS., et al.[2020]

Cytotoxic chemotherapy for recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC) primarily includes platinum agents, taxanes, and antimetabolic agents, which are commonly used to manage the disease.

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, shows modest effectiveness in treating R/M HNSCC, highlighting the importance of a multidisciplinary approach in palliative care planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current recommendations for systemic therapy of recurrent and/or metastatic head and neck squamous cell cancer. Fury, MG., Pfister, DG.[2019]

In a study of 143 patients with Stage III-IV head and neck squamous cell carcinoma, carboplatin-paclitaxel (CT) induction chemotherapy resulted in significantly better locoregional control (80.5%) and progression-free survival (73.2%) compared to docetaxel-cisplatin-5-fluorouracil (TPF) chemotherapy (55.5% and 60.7%, respectively).

TPF was associated with worse renal toxicity and a higher rate of chemotherapy dose reductions during treatment, suggesting that CT may be a safer and more effective option for patients undergoing induction chemotherapy before chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer. Herman, LC., Chen, L., Garnett, A., et al.[2021]

In a phase II trial involving 32 patients with recurrent or metastatic head and neck squamous cell carcinoma, the combination of carboplatin and raltitrexed demonstrated moderate efficacy, with a 22% partial response rate and a median survival duration of 9.8 months.

The treatment was generally safe, with manageable toxicity; however, 25% of patients experienced severe neutropenia, and one patient dropped out due to persistent hepatic toxicity, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.). Galetta, D., Giotta, F., Rosati, G., et al.[2014]

Chemotherapy, particularly when combined with radiotherapy, is crucial for managing head and neck cancers in patients with potentially curable disease.

New chemotherapy agents like paclitaxel or docetaxel combined with gemcitabine and cisplatin or carboplatin show promise and should be evaluated in phase III trials against traditional regimens, especially for their ability to enhance the effects of radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New cytostatic agents for the treatment of head and neck cancer. Devriendt, D., Klastersky, J.[2022]

References

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

Intravenous 5-Fluorouracil in Patients With Advanced Squamous Cell Carcinoma: A Retrospective Study. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Phase II trial of concurrent bio-chemoradiotherapy using docetaxel, cisplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma. [2018]

3. 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]

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

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. [2020]

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

Current recommendations for systemic therapy of recurrent and/or metastatic head and neck squamous cell cancer. [2019]

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

Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer. [2021]

7. Greece pubmed.ncbi.nlm.nih.gov

Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.). [2014]

8. Belgium pubmed.ncbi.nlm.nih.gov

New cytostatic agents for the treatment of head and neck cancer. [2022]