Chemotherapy Combinations for Head and Neck Cancer

((UPCI)13-056 Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Christopher T Wilke, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Christopher Wilke

Must not be taking: Antiretrovirals

Disqualifiers: Uncontrolled diabetes, Hypertension, Psychiatric illness, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to learn which chemotherapy combination may be more effective in treating locally advanced head and neck squamous cell carcinoma (HNSCC). The side effects of these combinations will also be studied. This study treatment consists of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. For study chemotherapy, patients will be randomized between cisplatin or the combination of docetaxel and cetuximab. Subjects will be stratified depending on HPV status and the presence of ERCC-1 \[4F9\] in the tumor prior to randomization. The study will evaluate cisplatin vs. docetaxel-cetuximab in the overall population, and test which radiation and chemotherapy combination works best in relationship to how much ERCC-1 \[4F9\] is expressed in a tumor.

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.

What data supports the effectiveness of the treatment combination of cetuximab, cisplatin, docetaxel, and IMRT for head and neck cancer?

Research shows that cetuximab combined with intensity-modulated radiation therapy (IMRT) is more effective than radiation alone for head and neck cancer. Additionally, docetaxel and cisplatin, when used together, have shown promising response rates and survival outcomes in treating this type of cancer. ^{1 2 3 4 5}

Is the combination of cetuximab, cisplatin, docetaxel, and IMRT safe for treating head and neck cancer?

The combination of cetuximab with radiotherapy has shown significant clinical benefits without increasing radiotherapy-associated toxicity. However, severe skin reactions (dermatitis) and other serious side effects like neutropenia (low white blood cell count) have been reported with these treatments, which can limit treatment adherence. Overall, while the treatments can be effective, they may come with serious side effects that need to be managed carefully. ^{3 4 6 7 8}

What makes the chemotherapy combination of Cetuximab, Cisplatin, Docetaxel, and IMRT unique for head and neck cancer?

This treatment is unique because it combines Cetuximab, a targeted therapy that blocks cancer cell growth signals, with Cisplatin and Docetaxel, which are chemotherapy drugs that kill cancer cells, and IMRT, a precise form of radiation therapy. This combination aims to enhance effectiveness while potentially reducing side effects compared to traditional chemotherapy regimens. ^{3 4 5 9 10}

Research Team

Christopher T Wilke, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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.

I had a tonsillectomy but still have measurable tumor or nodal disease.

Exclusion Criteria

Patient is living outside the US

I have had a condition where my lymphocytes grow abnormally.

I have a history of cancer.

Trial Timeline

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

Treatment Details

Interventions

• Cetuximab (Monoclonal Antibodies)
• Cisplatin (Alkylating agents)
• Docetaxel (Anti-microtubule agent)
• IMRT (Radiation)

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.

Participant Groups

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)

Who Is Running the Clinical Trial?

Christopher Wilke

Lead Sponsor

Trials

2

Recruited

140+

Heath Skinner

Lead Sponsor

Trials

4

Recruited

330+

Findings from Research

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 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 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 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]

References

1. United States 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. [2018]

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

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

3. France pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer. [2022]

4. 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]

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

Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. [2015]

7. England 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? [2015]

8. Switzerland 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. [2023]

9. 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]

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

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