Radiation + Drug for Oropharyngeal Cancer

No longer recruiting at 189 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether radiation therapy combined with either cisplatin or cetuximab is more effective for treating oropharyngeal cancer, which affects areas like the tonsils and the base of the tongue. Radiation therapy uses high-energy rays to target and kill cancer cells, while cisplatin and cetuximab are drugs that stop cancer growth in different ways. Participants must have a confirmed diagnosis of squamous cell carcinoma in the oropharynx and measurable cancer at the primary site or lymph nodes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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.

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

Research has shown that adding cetuximab to radiation therapy usually results in fewer severe side effects than adding cisplatin. One study found that cisplatin led to more serious side effects. Another study showed that 11.6% of patients receiving cisplatin with radiation died from causes unrelated to cancer progression, compared to 9.7% with cetuximab.

For cisplatin, earlier studies have reported high overall survival rates of about 96.7% when combined with radiation, but it is linked to more immediate serious side effects.

Both treatments are being tested in the trial to determine which works better with radiation for treating oropharyngeal cancer. The choice between them depends on how well a person can handle the side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination treatments of cetuximab and cisplatin with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer because they offer different mechanisms of action compared to traditional approaches. While cisplatin is a well-known chemotherapy drug that has been used to damage cancer cell DNA and stop their growth, cetuximab is a targeted therapy that works by blocking the epidermal growth factor receptor (EGFR) on cancer cells, which may inhibit tumor growth and spread. By combining these with IMRT, which precisely targets tumors while sparing surrounding healthy tissue, there is potential to enhance the effectiveness and reduce the side effects typically associated with standard treatments. This dual strategy of targeting both the cancer cell DNA and the receptors that promote cancer growth is what has researchers particularly optimistic.

What evidence suggests that this trial's treatments could be effective for oropharyngeal cancer?

Research has shown that using a type of radiation therapy called IMRT with the drug cisplatin helps oropharyngeal cancer patients live longer. Two recent studies found that this combination increased survival rates by 8% after five years compared to radiation alone. In this trial, one group of participants will receive IMRT with cisplatin. Conversely, IMRT with another drug, cetuximab, has demonstrated a very high success rate in shrinking tumors, with 99.3% of patients responding well four months after treatment. Another group in this trial will receive IMRT with cetuximab. Both treatments have strong potential to stop cancer growth and extend patient survival. The trial aims to determine which combination works better. ^{6 7 8 9 10}

Who Is on the 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

Are You a Good Fit for This Trial?

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

My liver and kidneys are working well.

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

I have been mostly active and able to carry on all pre-disease activities without restriction recently.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8037748/

Early Clinical Outcomes of Intensity Modulated Radiation ... The tumor response was excellent and the rates of overall and complete response, evaluated at 4 months of RT completion, were 99.3% and 85.1%, respectively.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301609005239

Intensity-Modulated Radiotherapy in the Treatment of ... IMRT provides excellent LRC for oropharyngeal squamous cell carcinoma. Distant metastases are a major failure pattern. No marginal failures were observed.

3. link.springer.com link.springer.com/article/10.1007/s42399-023-01562-5

Clinical Efficacy and Complications of Intensity-modulated ... Based on data from November 2022, the 5-year overall survival (OS) for OPC is reported to be 61.3% [5]. Intensity-modulated radiation therapy ( ...

4. redjournal.org redjournal.org/article/S0360-3016(15)02128-8/pdf

Intensity Modulated Radiation Therapy With Cetuximab ... In this report, we analyze nutritional factors and compliance with dietary recommendations for associations with overall survival (OS) and pro- gression-free ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00956007

NCT00956007 | RT With or Without Cetuximab in Treating ... PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with cetuximab in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5265923/

Cetuximab concurrent with IMRT versus cisplatin ... In our study, we found that regimens comprised of cisplatin plus radiation caused more severe adverse events compared with cetuximab plus ...

7. clinicaltrial.be clinicaltrial.be/en/details/76989?per_page=100&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

Radiation Therapy With Cisplatin or Cetuximab in Treating... OBJECTIVES: Primary. To determine whether substitution of cisplatin with cetuximab will result in comparable 5-year overall survival.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10247515/

Long-Term Update of NRG/RTOG 0522 In total, 52 patients (11.6%) in the RT/cisplatin arm and 43 patients (9.7%) in the RT and cisplatin/cetuximab arm had death without progression due to study ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01302834

Radiation Therapy With Cisplatin or Cetuximab in Treating ... 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.

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1368837515002559

Weekly cetuximab concurrent with IMRT aggravated ... The 3-year disease-free survival (DFS) were achieved as 78.3% and 85.7% (P = 0.547) in CRT and ERT arm, respectively. In the analysis of QoL, the addition of ...