Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With HPV Positive, KRAS-Variant Stage III-IV Oropharyngeal Squamous Cell Carcinoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

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

Trial Summary

What is the purpose of this trial?

This trial studies how well radiation therapy and cisplatin with or without cetuximab work in treating patients with a specific type of throat cancer. The treatment combines high-energy rays, chemotherapy, and immunotherapy to kill cancer cells and help the immune system fight the cancer. Cetuximab is a cornerstone of treatment due to the large role of epidermal growth factor receptor in laryngeal and hypopharyngeal carcinomas. The goal is to see if this combination works better than radiation and chemotherapy alone.

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.

What data supports the effectiveness of the drug Cetuximab in combination with other treatments?

Cetuximab has shown effectiveness in improving survival and response rates when used with other treatments, like FOLFIRI, in patients with certain types of colorectal cancer. Additionally, it may enhance the effects of radiotherapy in some cancers, although more research is needed to confirm these benefits in other conditions. ^{1 2 3 4 5}

What safety data exists for cetuximab and related treatments?

Cetuximab, when used with radiotherapy, can cause significant side effects like severe mouth sores, skin reactions, weight loss, and the need for feeding tubes. These side effects are more pronounced compared to using cisplatin with radiotherapy. Additionally, combining cetuximab with radiotherapy can lead to skin toxicity, which requires careful management. ^{1 6 7 8 9}

How is the treatment with Cetuximab, Cisplatin, and Radiation Therapy different from other treatments for this condition?

This treatment combines Cetuximab, which targets the epidermal growth factor receptor (EGFR) to enhance the effects of radiation, with Cisplatin and radiation therapy, potentially offering a more effective and tolerable option compared to traditional chemoradiotherapy that often has severe side effects. Cetuximab has shown promise in improving outcomes without increasing radiation-related toxicity, making it a unique alternative for patients who may not tolerate standard platinum-based regimens. ^{1 6 10 11 12}

Research Team

Robert K Chin

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

Interventions

• Cetuximab
• Cisplatin
• Radiation Therapy

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

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

Phase II Trial of Cetuximab and Conformal Radiotherapy Only in Locally Advanced Pancreatic Cancer with Concurrent Tissue Sampling Feasibility Study. [2021]

2. New Zealand 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Cetuximab. [2020]

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

Radioactive EGFR antibody cetuximab in multimodal cancer treatment: stability and synergistic effects with radiotherapy. [2018]

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

Assessing Care Value for Older Patients Receiving Radiotherapy With or Without Cisplatin or Cetuximab for Locoregionally Advanced Head and Neck Cancer. [2023]

6. 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]

7. Ireland pubmed.ncbi.nlm.nih.gov

Toxicity of cetuximab versus cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer (LAHNSCC). [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Management of 'in-field' skin toxicity in head and neck cancer patients treated with combined cetuximab and radiotherapy. [2018]

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

TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial. [2022]

10. 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]

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

Cetuximab-Based vs Carboplatin-Based Chemoradiotherapy for Patients With Head and Neck Cancer. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Is the combination of Cetuximab with chemo-radiotherapy regimens worthwhile in the treatment of locally advanced head and neck cancer? A review of current evidence. [2015]