Radiation and Cisplatin ± Cetuximab for Oropharyngeal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: EGFR inhibitors

Disqualifiers: Metastatic cancer, Prior radiation, 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: 2

Duration: 6-7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a combination of treatments for individuals with HPV-positive oropharyngeal cancer that has a specific genetic marker (KRAS-variant). The trial compares the use of radiation therapy and the chemotherapy drug cisplatin, with or without the addition of cetuximab, an immunotherapy drug that may help the body combat cancer. Ideal candidates for this trial include those with newly diagnosed HPV-positive oropharyngeal cancer who have not received prior treatment and have a limited smoking history. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

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.

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

Research has shown that cetuximab, when combined with radiation therapy and cisplatin, has been studied for safety. Reports indicate that most patients generally tolerate this combination well. However, the safety of cetuximab with these treatments remains under investigation, and information is still limited. The FDA has approved cetuximab for other uses, suggesting a degree of safety, but specific side effects and risks may still occur with this combination.

Cisplatin and radiation therapy are well-established treatments and have been used together for a long time. Most people tolerate these treatments well, though they can cause side effects like nausea or fatigue. While some safety information is available for cetuximab when used with cisplatin and radiation therapy, ongoing research is crucial to better understand its safety in this specific context. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for HPV-positive, KRAS-variant stage III-IV oropharyngeal squamous cell carcinoma typically involve radiation therapy combined with chemotherapy, like cisplatin. But researchers are excited about adding cetuximab to this mix because it introduces a new mechanism of action. Cetuximab is a monoclonal antibody that specifically targets the epidermal growth factor receptor (EGFR), which is involved in the growth and spread of cancer cells. By targeting EGFR, cetuximab can potentially enhance the effectiveness of radiation and cisplatin, offering a more tailored approach to treating this specific type of cancer.

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

This trial will compare two treatment approaches for head and neck cancer. One group will receive radiation therapy combined with cisplatin. The other group will receive cetuximab in addition to radiation therapy and cisplatin. Studies have shown that adding cetuximab to radiation therapy or cisplatin can extend the lives of patients with head and neck cancer. Specifically, using cetuximab with radiation therapy has been linked to a noticeable increase in survival rates. Cetuximab has also proven effective for patients with squamous-cell carcinoma, a type of head and neck cancer, even when other treatments have failed. This suggests that cetuximab might improve treatment outcomes for patients with certain types of this cancer, such as those linked to HPV or specific genetic variations. ^{6 7 8 9 10}

Who Is on the Research Team?

Robert K Chin

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Inclusion Criteria

Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2 x the institutional upper limit of normal (ULN) (within 2 weeks prior to registration)

Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits, and examinations including follow up

Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluation

Exclusion Criteria

Patients with prior radiation therapy (RT) that would result in overlap of radiation therapy treatment fields (superficial x-ray of skin lesions excluded)

History of another primary invasive malignancy except for: Malignancy treated with curative intent and with no known active disease >= 3 years before the first dose of study drug and of low potential risk for recurrence, Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, Adequately treated low risk prostate cancer without evidence of disease, Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ, and ductal breast carcinoma in situ (DCIS)

Patients with uncontrolled or poorly-controlled hypertension (> 180 mmHg systolic or > 130 mmHg diastolic)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo radiation therapy over 6 weeks with concurrent cisplatin, and in Arm II, cetuximab is administered weekly for 7 weeks

6-7 weeks

Weekly visits for radiation and chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Follow-up at 2-4 weeks post-treatment, every 12 weeks for 2 years, then every 3-12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Cisplatin
• Radiation Therapy

How Is the Trial Designed?

Group I: Arm II (cetuximab, radiation therapy, cisplatin) Experimental Treatment 5 Interventions

Patients receive cetuximab IV over 120 minutes 5-7 days prior to start of radiation therapy and then IV over 60 minutes weekly on Monday or Tuesday for 7 weeks. Patients also undergo radiation therapy and receive cisplatin as in Arm I.

Group II: Arm I (radiation therapy, cisplatin) Active Control 4 Interventions

Beginning on day 0, patients undergo radiation therapy over 6 weeks for a total of 35 fractions. Patients also receive cisplatin IV over 1-2 hours on days 0 and 21.

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?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

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]

Cetuximab, a monoclonal antibody targeting the EGFR, has been approved for first-line treatment of KRAS mutation-negative metastatic colorectal cancer (mCRC) in combination with FOLFIRI, showing significant improvements in progression-free survival and overall survival.

The combination of cetuximab with FOLFIRI also resulted in higher objective response rates compared to FOLFIRI alone, making it a valuable treatment option for patients with EGFR-expressing, KRAS wild-type mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. Lyseng-Williamson, KA.[2021]

The study demonstrated that radiolabeled cetuximab (131I-Erbi) is stable for up to 72 hours and shows significantly higher uptake in cancer cells with epidermal growth factor receptors, indicating its potential effectiveness in targeting brain metastases.

Combining radiotherapy with 131I-Erbi resulted in a greater inhibition of tumor cell proliferation compared to using cetuximab alone, suggesting a synergistic effect that could enhance treatment outcomes for patients with multiple brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioactive EGFR antibody cetuximab in multimodal cancer treatment: stability and synergistic effects with radiotherapy. Rades, D., Wolff, C., Nadrowitz, R., et al.[2018]

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39869839/

Correlates of Cetuximab Efficacy in Recurrent and ... Results: We identified 70 patients treated with cetuximab after an ICI. The mean age was 67.6 years, with 60% having virus-associated HNSCC.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2745918/

The Role of Cetuximab for the Treatment of Squamous Cell ... Cetuximab is an active drug in head and neck cancer, with randomized trial evidence that it improves survival when given with radiotherapy or cisplatin ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa0802656

Platinum-Based Chemotherapy plus Cetuximab in Head ... Cetuximab is effective in recurrent or metastatic squamous-cell carcinoma of the head and neck that progresses despite platinum-containing therapy.

4. news.bms.com news.bms.com/news/details/2008/ERBITUXR-Five-Year-Data-Show-Significant-Improvement-in-Overall-Survival-for-Patients-with-Locally-or-Regionally-Advanced-Head-and-Neck-Cancer/default.aspx

ERBITUX(R) Five-Year Data Show Significant ... These five-year data demonstrate that the addition of ERBITUX to radiation therapy resulted in a significant increase in median overall survival for patients ...

5. ascopubs.org ascopubs.org/doi/abs/10.1200/PO-24-00741

Correlates of Cetuximab Efficacy in Recurrent and ... Correlates of Cetuximab Efficacy in Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Previously Treated With Immunotherapy.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/125084s273lbl.pdf

ERBITUX (cetuximab) - accessdata.fda.gov In Combination with Radiation Therapy. The safety of ERBITUX in combination with radiation therapy compared to radiation therapy alone was evaluated in. BONNER.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0360301625039082

Chemoradiation therapy With Cisplatin Versus Cetuximab ... The study showed inferior treatment outcomes for cetuximab compared with cisplatin concurrent with RT. Cisplatin remains standard concomitant treatment for ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31242489/

Efficacy and Safety of Cetuximab plus Radiotherapy in ... Cetuximab plus radiotherapy appears to be feasible and active in elderly patients unsuitable for cisplatin treatment.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00265941

Study Details | NCT00265941 | Radiation Therapy and ... Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2009/125084s168lbl.pdf

Erbitux (cetuximab) label - accessdata.fda.gov ] 5.5. Use of Erbitux in Combination With Radiation and. Cisplatin. The safety of Erbitux in combination with radiation therapy and cisplatin has not been.