Chemotherapy Combinations for Head and Neck Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which combination of chemotherapy drugs best treats locally advanced head and neck squamous cell carcinoma. Researchers are testing various drug combinations, including Carboplatin, Cetuximab, Cisplatin, Docetaxel, Fluorouracil, and Paclitaxel, to evaluate their effectiveness and potential side effects. Participants will receive chemotherapy and radiation in different sequences, based on their assigned group. The trial seeks individuals diagnosed with specific types of head and neck cancer who have not previously undergone chemotherapy or radiation in that area. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments in this study have undergone previous testing. For the PCC treatment plan, results have been mixed. Some patients experienced fewer severe side effects with weekly administration. However, about 45% of patients delayed treatment due to side effects, and 27% discontinued because of serious issues.

The C-TPF treatment plan has also been studied. Most patients completed the treatment, but some experienced significant side effects, mainly affecting the stomach and skin.

Both treatments have been used before, providing some understanding of their effects. However, side effects can vary among individuals. This study aims to provide more insight into how well people can tolerate these drug combinations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these chemotherapy combinations for head and neck cancer because they bring together multiple powerful drugs to attack the cancer in different ways. Unlike the standard of care, which often involves single-drug treatments, this approach uses combinations like Paclitaxel, Carboplatin, and Cetuximab (PCC), and Cetuximab, Docetaxel, Cisplatin, and Fluorouracil (C-TPF) to potentially enhance effectiveness. These combinations are designed to improve how the body responds to radiation therapy, potentially resulting in more effective cancer control. By integrating these drugs with radiation, the treatments aim to maximize the cancer-killing effects while potentially reducing the chance of resistance. The hope is that such a multi-pronged approach could lead to better outcomes for patients.

What evidence suggests that this trial's chemotherapy combinations could be effective for head and neck cancer?

Research shows that the PCC combination—Paclitaxel, Carboplatin, and Cetuximab—yields promising results for treating head and neck squamous cell carcinoma. Studies highlight that this combination is effective and generally well-tolerated by patients, with a good success rate in the early stages of treatment. In this trial, participants in the PCC Group will receive this combination along with radiation therapy, with some also receiving additional chemotherapy.

Trials also report encouraging outcomes for the C-TPF combination—Cetuximab, Docetaxel, Cisplatin, and Fluorouracil. These studies suggest that this combination may extend patients' lives, offering significant benefits. Participants in the C-TPF Group in this trial will receive this combination with radiation therapy, and some will also receive additional chemotherapy. Both treatments are under study for their potential to improve outcomes in head and neck cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Renata Ferrarotto, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33684370/

Cetuximab, docetaxel, and cisplatin versus platinum ... Results from a phase 2 trial of the TPEx chemotherapy regimen (docetaxel-platinum-cetuximab) showed promising results, with a median overall survival of 14·0 ...

2. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30755-5/abstract

Cetuximab, docetaxel, and cisplatin versus platinum ... Results from a phase 2 trial of the TPEx chemotherapy regimen (docetaxel–platinum–cetuximab) showed promising results, with a median overall ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.6027

Induction chemotherapy with docetaxel, cisplatin and ... Here we report promising results of a randomized phase II trial comparing TPF with TP and Cetuximab (C) replacing F.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419317685

Cetuximab, docetaxel, and cisplatin as first-line treatment ... This study evaluated the efficacy and safety of four cycles of docetaxel associated with cisplatin and cetuximab (TPEx), followed by maintenance with cetuximab ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02268695

Study Details | NCT02268695 | Platinum-Cetuximab ... This study evaluates the efficacy of the new docetaxel-cisplatin-cetuximab regimen (TPEx) versus the standard platinum-5FU-cetuximab EXTREME regimen as a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4430265/

Induction therapy with cetuximab plus docetaxel, cisplatin ... The all nine planned cetuximab doses and the full three doses of planned chemotherapy were completed in 31 (76%) and 36 (88%) patients, ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa071028

Cisplatin, Fluorouracil, and Docetaxel in Unresectable ... Our study showed that induction chemotherapy with TPF resulted in significant and clinical meaningful improvements in outcomes, as compared with ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT129774

Cetuximab (C), fluorouracil (F), and cisplatin (P) alone or ... Background: This trial was based on the findings that D in addition to PF in induction treatment and C in addition to PF in RM disease both improved outcome ...

9. ascopubs.org ascopubs.org/doi/10.1200/jco.2008.26.15_suppl.6001

Cetuximab added to docetaxel, cisplatin, 5-fluorouracil ... Conclusion: C-TPF appears to be safe and feasible as given in this study. GI toxicity appears to be the major combined DLT. Skin rash is frequent and limits C ...