Chemotherapy Combinations for Head and Neck Cancer

((UPCI)13-056 Trial)

Recruiting at 1 trial location

Overseen By Samantha Demko, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Christopher Wilke

Must not be taking: Antiretrovirals

Disqualifiers: Uncontrolled diabetes, Hypertension, Psychiatric illness, 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: Unknown

Duration: 7 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates which chemotherapy combination is most effective for treating squamous cell carcinoma, a type of head and neck cancer. Participants will receive radiation therapy along with one of two chemotherapy options: cisplatin or a combination of docetaxel and cetuximab, a targeted therapy drug. The trial will also examine the side effects of these treatments and their effectiveness based on specific tumor characteristics. Ideal participants are those diagnosed with locally advanced head and neck cancer who have not yet undergone chemotherapy or radiation. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on anti-retroviral therapy for HIV, you cannot participate in this study due to possible drug interactions.

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

Research shows that both chemotherapy combinations being tested have been studied for safety in people with head and neck cancer. Studies indicate that the Cisplatin-IMRT combination can improve survival rates when used with radiation therapy, though it may cause side effects like hearing loss, especially at higher doses. Careful dose management generally ensures it is well-tolerated.

Past research suggests that the Docetaxel-Cetuximab-IMRT combination, with cetuximab, can enhance treatments for head and neck cancer. This combination has shown promise in improving outcomes but can also lead to side effects, such as skin reactions and low blood cell counts, which may affect the immune system. Overall, these treatments are considered safe when monitored by medical professionals, though they carry some risks.

Participating in a trial means these treatments are not yet fully approved for this specific use, so ongoing research is crucial to better understand their safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they combine chemotherapy with Intensity-Modulated Radiation Therapy (IMRT) in innovative ways. Unlike the standard care that typically involves single-agent chemotherapy or radiation, the Cisplatin-IMRT arm uses Cisplatin weekly alongside daily IMRT sessions, potentially enhancing the effectiveness of radiation by making cancer cells more sensitive to it. The Docetaxel-Cetuximab-IMRT arm is particularly intriguing as it involves a combination of Docetaxel and Cetuximab, which targets the epidermal growth factor receptor (EGFR) on cancer cells, combined with IMRT. This approach aims to improve targeting of cancer cells while minimizing damage to surrounding healthy tissues, offering a potentially more effective and less toxic treatment option.

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

Studies have shown that using cisplatin with intensity-modulated radiation therapy (IMRT) can effectively treat squamous cell carcinoma, a type of head and neck cancer. Research suggests that this combination may extend patient survival compared to radiation alone. In this trial, one group of participants will receive the cisplatin-IMRT combination. Another option being explored is the combination of docetaxel and cetuximab with IMRT. Cetuximab has demonstrated benefits when used with radiation for head and neck cancer. Both treatment combinations are under study in this trial, and each has shown promise in improving outcomes for patients with this cancer type. ^{1 3 4 5 6}

Who Is on the Research Team?

Christopher T Wilke, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults with advanced head and neck squamous cell carcinoma (HNSCC) without distant metastasis. They must have stage III, IVa or IVb disease, be untreated by surgery for their current diagnosis, and not have had chemotherapy or radiation for HNSCC before. Those with a second HNSCC more than 2 years apart treated only by surgery are eligible; however, those with simultaneous primaries or bilateral tumors (except certain cases) cannot join.

Inclusion Criteria

My cancer is a specific type in the throat and has not spread far.

My cancer is at stage III, IVa, or IVb.

Diagnostic primary tumor tissue must be available for ERCC1 staining

Exclusion Criteria

Patient is living outside the US

I have had a condition where my lymphocytes grow abnormally.

I have a history of cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with either cisplatin or the combination of docetaxel and cetuximab for 7 weeks

7 weeks

Weekly visits for chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Cisplatin
• Docetaxel
• IMRT

Trial Overview The study compares the effectiveness of two chemotherapy combinations in treating locally advanced HNSCC: one group receives IMRT with cisplatin while the other gets IMRT combined with docetaxel and cetuximab. Participants will be sorted based on HPV status and ERCC-1 levels in their tumor to see which treatment works best relative to these factors.

How Is the Trial Designed?

Group I: Cisplatin-IMRT Active Control 2 Interventions

Cisplatin 40 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)

Group II: Docetaxel-Cetuximab-IMRT Active Control 3 Interventions

Docetaxel 15 mg/m2 weekly x 7; Cetuximab 400 mg/m2 load, one week prior to IMRT; Cetuximab 250 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)

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

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer

Who Is Running the Clinical Trial?

Christopher Wilke

Lead Sponsor

Trials

2

Recruited

140+

Heath Skinner

Lead Sponsor

Trials

4

Recruited

330+

Published Research Related to This Trial

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]

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 erlotinib and docetaxel with intensity-modulated radiotherapy (IMRT) showed promising efficacy in treating locally advanced head and neck squamous cell carcinoma, with a 3-year disease-free survival rate of 69.5% and overall survival rate of 81% based on a study of 43 patients over a median follow-up of 48.7 months.

The treatment was generally well-tolerated, although some patients experienced significant toxicities such as dysphagia, dermatitis, and mucositis, indicating that this regimen could be a viable option for patients who cannot tolerate cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of erlotinib and docetaxel with concurrent intensity-modulated radiotherapy in locally advanced head and neck squamous cell carcinoma. Yao, M., Woods, C., Lavertu, P., et al.[2018]

In a study of 99 head-and-neck cancer patients receiving simultaneous integrated boost intensity-modulated radiotherapy with cetuximab, 34% experienced severe dermatitis (Grade 3/4), significantly higher than the 3% in a control group treated with cisplatin.

There was a clear link between the radiation dose to the skin and the severity of dermatitis in patients receiving cetuximab, indicating that higher radiation exposure increases the risk of severe skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. Studer, G., Brown, M., Salgueiro, EB., et al.[2015]

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]

Adding the EGFR inhibitor cetuximab to radiotherapy for locally advanced squamous cell carcinoma of the head and neck significantly improves clinical outcomes without increasing the toxicity associated with radiotherapy.

Current chemoradiotherapy regimens, which are often platinum-based, have reached a limit in tolerable toxicity, highlighting the need for more effective and tolerable treatment options like cetuximab combined with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squamous cell carcinomas of the head and neck? Bernier, J., Schneider, D.[2015]

In a study of 180 patients with head and neck cancer, those treated with cetuximab experienced significantly higher rates of acute dermal toxicity (34.5%) compared to those who did not receive cetuximab (10.3%).

Despite the increased skin toxicity, there were no significant differences in local control or overall survival between patients treated with cetuximab and those treated without it, indicating that cetuximab does not improve survival outcomes when combined with IMRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer. Bibault, JE., Morelle, M., Perrier, L., et al.[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]

Docetaxel shows promising efficacy as a treatment for recurrent squamous cell cancer of the head and neck, with response rates between 33% to 44% when combined with cisplatin, and median survival times of 9.6 to 11 months.

In the neoadjuvant setting, docetaxel has demonstrated response rates greater than 90%, indicating its potential for improving disease-free and overall survival, with ongoing trials comparing its effectiveness to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. Glisson, BS.[2018]

In a case series of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), a combination treatment of paclitaxel, carboplatin, cetuximab, and pembrolizumab resulted in significant clinical responses, with all patients achieving an objective response (6 complete responses and 2 partial responses).

The treatment was generally safe, with manageable adverse events, although one patient experienced liver toxicity related to the immune checkpoint inhibitor. This suggests that the quadruple therapy could be a promising option for R/M HNSCC, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Response Rate to Carboplatin-Paclitaxel-Cetuximab and Pembrolizumab in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Chauffert, B., Zhou, Y., Medjkoune, L., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3028434/

Comprehensive IMRT Plus Weekly Cisplatin for Advanced ... Comprehensive head and neck IMRT to 70 Gy delivered with weekly cisplatin chemotherapy (30 mg/m 2 ) is feasible and generally well tolerated.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2827612

Weekly Cisplatin Cycles and Outcomes for Chemoradiation ... These findings suggest that missing several cycles of weekly cisplatin is associated with worse survival, even among those with p16-negative tumors.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-00528

Cisplatin and Intensity-Modulated Radiation Therapy in ... Giving cisplatin and intensity-modulated radiation therapy may work better in treating patients with head and neck squamous cell carcinoma.

4. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00599-1/fulltext

Standard versus fractionated high-dose cisplatin plus ... In the standard arm (HD-Cis), patients received cisplatin at a dose of 100 mg/m2 every 3 weeks for 3 cycles on D1, D22, and D43 of radiotherapy.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1368837511008608

Weekly and 3-weekly cisplatin concurrent with intensity- ... Concurrent 3-weekly cisplatin improves overall survival (OS) compared to radiotherapy alone, but is often associated with renal toxicity.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38927933/

Audiological Outcomes of Weekly vs. Triweekly Cisplatin in ... Triweekly cisplatin CRT significantly increased the ≥G3 severe irreversible ototoxicity risk compared to low-dose weekly cisplatin.