Radiation + Drug for Oropharyngeal Cancer

Recruiting at 184 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Radiation Therapy Oncology Group

Must not be taking: Anti-EGFR therapy

Disqualifiers: Oral cancers, Metastasis, Severe comorbidities, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

987 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether radiation therapy is more effective with cisplatin or cetuximab in treating oropharyngeal cancer. PURPOSE: This phase III trial is studying radiation therapy with cisplatin or cetuximab to see how well it works in treating patients with oropharyngeal cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

What data supports the effectiveness of this treatment for oropharyngeal cancer?

Research shows that combining cetuximab with radiation therapy, like IMRT, can be an effective treatment for oropharyngeal cancer, especially for patients who cannot use cisplatin. However, studies indicate that platinum-based treatments may have better overall survival rates compared to cetuximab with radiation. ^{1 2 3 4 5}

Is the combination of radiation and cetuximab safe for treating oropharyngeal cancer?

The combination of radiation and cetuximab for treating oropharyngeal cancer has been associated with some safety concerns. Studies have reported serious skin reactions (dermatitis) and increased risks of death and cancer recurrence compared to other treatments. It's important to discuss these potential risks with your healthcare provider. ^{3 6 7 8 9}

How is the treatment of radiation plus cetuximab and cisplatin unique for oropharyngeal cancer?

This treatment combines radiation with cetuximab and cisplatin, offering an alternative for patients who may not tolerate cisplatin alone. Cetuximab, an antibody targeting the epidermal growth factor receptor, is used to potentially reduce toxicity while maintaining high survival rates, especially in HPV-positive oropharyngeal cancer. ^{1 2 8 9 10}

Research Team

Andy M. Trotti, MD

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Maura Gillison, MD, PhD

Principal Investigator

Ohio State University

Eligibility Criteria

Adults with oropharyngeal cancer, specifically squamous cell carcinoma, who haven't had prior chemotherapy or radiotherapy for it. They should have a good performance status and no severe health issues like recent heart attacks or uncontrolled infections. HIV-positive patients can join if they don't have AIDS-defining conditions.

Inclusion Criteria

I am 18 years old or older.

Complete blood count (CBC)/differential obtained within 2 weeks prior to registration

My liver and kidneys are working well.

Exclusion Criteria

I have received chemotherapy for my current cancer.

I have had radiation in the same area where my current cancer is located.

All of my cancer and affected lymph nodes have been surgically removed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intensity-modulated radiotherapy (IMRT) with concurrent cisplatin or cetuximab

6 weeks

Weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

1-3 months post-treatment, then every 3 months for 2 years, every 6 months for 3 years, and annually thereafter

Treatment Details

Interventions

• Cetuximab
• Cisplatin
• IMRT

Trial Overview This trial is testing whether radiation therapy combined with either cisplatin (a chemotherapy drug) or cetuximab (a monoclonal antibody that targets cancer cells) is more effective in treating patients with cancers of the throat area.

Participant Groups

Group I: IMRT + Cisplatin Active Control 2 Interventions

Intensity-modulated radiotherapy (IMRT) with concurrent cisplatin

Group II: IMRT + Cetuximab Active Control 2 Interventions

Intensity-modulated radiotherapy (IMRT) with concurrent cetuximab

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?

Radiation Therapy Oncology Group

Lead Sponsor

Trials

191

Recruited

64,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

Patients with locally advanced oropharyngeal squamous cell carcinoma who received cisplatin (CDDP) had a significantly better 2-year overall survival rate compared to those treated with cetuximab (CTX), with a hazard ratio of 1.68 indicating higher mortality for CTX users.

Cisplatin also resulted in lower overall treatment costs compared to CTX and carboplatin, despite higher rates of antiemetic use and hospital visits for side effects, suggesting it may be a more cost-effective option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma. Amini, A., Eguchi, M., Jones, BL., et al.[2023]

Intensity modulated radiation treatment (IMRT) for oropharyngeal squamous cell carcinoma showed excellent locoregional control, with a 3-year locoregional progression-free survival rate of 98.8% among 66 patients treated between 2000 and 2004.

Despite the high locoregional control, there was a concerning rate of distant metastasis, with a 3-year distant metastasis-free survival rate of only 80.4%, indicating a need for further research into systemic treatments for patients at risk of distant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. Yao, M., Nguyen, T., Buatti, JM., et al.[2006]

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]

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]

References

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

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma. [2023]

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

Paired phase II trials evaluating cetuximab and radiotherapy for low risk HPV associated oropharyngeal cancer and locoregionally advanced squamous cell carcinoma of the head and neck in patients not eligible for cisplatin. [2021]

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

Platinum-based regimens versus cetuximab in definitive chemoradiation for human papillomavirus-unrelated head and neck cancer. [2021]

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

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. [2006]

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

Treatment of locally advanced carcinomas of head and neck with intensity-modulated radiation therapy (IMRT) in combination with cetuximab and chemotherapy: the REACH protocol. [2021]

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. 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]

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

Concurrent Cetuximab-based bioradiotherapy versus Cisplatin-based Chemoradiotherapy in the Definitive Management of Favourable Biology Human Papillomavirus-associated Oropharyngeal Squamous Cell Carcinoma: Systematic Review and Meta-analysis. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Adjuvant therapy with cetuximab for locally advanced squamous cell carcinoma of the oropharynx: results from a randomized, phase II prospective trial. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. [2022]