Neck Radiation +/− Cisplatin for Oropharyngeal Cancer

Overseen By Ryan Romasko

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Disqualifiers: Metastatic disease, Prior head/neck surgery, 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: Unknown

Duration: 6-7 weeks

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of neck radiation and the chemotherapy drug Cisplatin to evaluate their effectiveness in treating oropharyngeal cancer, particularly in patients with p16-positive cancer. Researchers aim to determine how well these treatments work for patients with cancer confined to one side of the neck or with specific lymph node involvement. Suitable candidates for this trial have been diagnosed with squamous cell carcinoma in the oropharynx, have a history of smoking, and have specific lymph node conditions without cancer crossing the midline of the neck. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 study team or your doctor.

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

Previous studies have shown that cisplatin plays an important role in treating HPV-positive oropharyngeal cancer. While effective, it can cause side effects such as painful mouth sores, nausea, vomiting, and a decrease in white blood cells, which help fight infections.

Radiation therapy, another component of this trial, also causes side effects. Patients often experience soreness or dryness in their mouths. Despite these effects, radiation therapy remains a well-established treatment for this type of cancer.

Both treatments have a well-documented safety record. Although side effects are known, they can usually be managed. Joining the trial will help researchers learn more about balancing the benefits and side effects for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores combining neck radiation with cisplatin for treating oropharyngeal cancer. Unlike standard treatments that often use radiation alone or chemotherapy separately, this approach investigates the potential benefits of using them together, which might enhance effectiveness against cancer cells. Cisplatin is a powerful chemotherapy drug that can damage the DNA of cancer cells, potentially making them more sensitive to radiation. This trial aims to determine whether this combination can improve outcomes, especially for patients with more extensive neck cancer involvement.

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

This trial will compare the effectiveness of neck radiation with or without the addition of cisplatin for treating oropharyngeal cancer. Research has shown that cisplatin effectively treats p16+ oropharyngeal cancer. Studies have found that patients have better survival rates when they receive the right amount of cisplatin. Specifically, those who received a total dose of 200 mg or more had higher overall survival rates, with 89.7% having no detectable cancer afterward.

Radiation therapy, particularly intensity-modulated radiation therapy (IMRT), plays a crucial role in treating oropharyngeal cancer. It protects organs while effectively managing the cancer. Survival rates are high, and it has a strong record of preventing cancer recurrence. Together, these treatments offer a promising approach for people with p16+ oropharyngeal cancer. Participants in this trial will receive either radiation therapy alone or in combination with cisplatin, depending on their assigned cohort. ^{3 6 7 8 9}

Who Is on the Research Team?

Thomas Galloway, MD

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with p16+ oropharyngeal cancer, who have not had prior systemic therapy or neck surgery for the cancer. They should be in good physical condition (ECOG 0-1), without metastatic disease, bilateral neck adenopathy, or a history of severe allergic reactions to Technetium-99m-tilmanocept. Tumors must not cross midline and patients should have adequate organ function.

Inclusion Criteria

My blood, kidney, and liver tests are normal.

CT with contrast and/or MRI with contrast performed within 56 days prior to registration showing no bilateral neck adenopathy

PET/CT performed within 28 days prior to registration showing no bilateral neck adenopathy

Exclusion Criteria

Pregnant or breastfeeding

I have received systemic therapy for my cancer.

History of allergic reaction to Technetium-99m-tilmanocept

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Patients positive for p16 status are approached for consent during the pre-treatment intake process

1 week

Treatment

Participants receive unilateral neck radiation for 6-7 weeks or until unacceptable toxicity or withdrawal of consent

6-7 weeks

Follow-up

Participants are monitored for disease free survival (DFS) and overall survival (OS) until 24 months after completion of study treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Radiation Therapy

Trial Overview

The study tests elective neck radiation directed by lymphoscintigraphy in p16+ favorable risk oropharynx cancer patients. It's a phase II trial where participants receive either 6 weeks of daily radiation with cisplatin, or an extended 7-week course if needed based on tumor mapping.

How Is the Trial Designed?

Group I: Cohort B (N0 or N1 <3cm) Experimental Treatment 1 Intervention

For Cohort B patients need to have either no lymph nodes or only one lymph node adenopathy, provided it is smaller than 3cm.

Group II: Cohort A (>N1 or single node > 3cm ) Experimental Treatment 2 Interventions

More extensive neck involvement or proximity to the midline can qualify a patient in cohort A. Cohort A will have patients with either more than one lymph node adenopathy or 1 lymph node that is large (\>3cm).

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Cardinal Health

Industry Sponsor

Trials

12

Recruited

2,800+

Published Research Related to This Trial

In a study of 21 patients with advanced oropharyngeal carcinoma, selective intraarterial chemoradiation therapy using high-dose cisplatin (300 mg/m²) resulted in a 2-year overall survival rate of 71.3% for those who completed the treatment.

The therapy also achieved a high locoregional control rate of 95.0% and a disease-free survival rate of 67.7%, indicating its efficacy while potentially reducing the number of treatment procedures compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective intraarterial chemoradiation therapy for oropharyngeal carcinoma with high-dose cisplatin. Nishio, R., Saito, K., Ito, H., et al.[2021]

In a phase III trial involving 891 patients with stage III or IV head and neck carcinoma, adding cetuximab to the radiation-cisplatin treatment did not improve progression-free survival (PFS) or overall survival (OS) compared to radiation-cisplatin alone.

Patients with p16-positive oropharyngeal carcinoma had significantly better PFS and OS compared to those with p16-negative tumors, indicating that p16 status is a more important factor for outcomes than the addition of cetuximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. Ang, KK., Zhang, Q., Rosenthal, DI., et al.[2022]

Modern radiation therapy, particularly intensity-modulated radiation therapy (IMRT), significantly reduces xerostomia (dry mouth) and improves the quality of life for patients with oropharyngeal cancer.

Intensity-modulated proton therapy may offer even greater benefits by minimizing radiation-related toxicities, which is crucial for patients with HPV-positive oropharyngeal carcinoma who are likely to have long-term survival after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in radiation oncology for the management of oropharyngeal tumors. Gunn, GB., Frank, SJ.[2018]

Carboplatin-based chemoradiation therapy (CTRT) is a well-tolerated alternative for patients with locally advanced head and neck cancers who are unfit for cisplatin, with 84.1% of patients completing the planned treatment.

The study found a median overall survival of 28 months and progression-free survival of 17 months, suggesting that carboplatin-based CTRT may offer better outcomes compared to radical radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin-based concurrent chemoradiation therapy in locally advanced head and neck cancer patients who are unfit for cisplatin therapy. Noronha, V., Sharma, V., Joshi, A., et al.[2018]

Intensity Modulated Radiation Therapy (IMRT) combined with Image Guided Radiation Therapy (IGRT) enhances treatment for head and neck cancer by improving tumor coverage while minimizing damage to normal tissues, leading to similar tumor control rates with less toxicity compared to conventional methods.

In the context of systemic therapy, platinum-based radiochemotherapy remains the standard treatment, and early evidence suggests that adding Cetuximab to cisplatin-based therapy does not provide additional benefits in primary treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies in radiotherapy of head and neck cancer. Pütz, M., Wenz, F.[2021]

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 83 patients with oropharyngeal, hypopharyngeal, or laryngeal cancer, treatment with weekly cisplatin during radiotherapy resulted in a 2-year local control rate of 84% and overall survival rate of 82%.

The 5-year survival estimates showed a local control rate of 79%, overall survival of 69%, and disease-specific survival of 76%, indicating that this treatment regimen is effective over the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of relapse following definitive treatment of head and neck squamous cell cancer by intensity modulated radiotherapy and weekly cisplatin. Loimu, V., Collan, J., Vaalavirta, L., et al.[2019]

In a phase III trial involving 237 patients with inoperable head and neck cancer, intra-arterial (IA) cisplatin did not show improved tumor control compared to intravenous (IV) cisplatin, despite a higher dose being administered via IA.

Patients receiving IV cisplatin experienced worse late dysphagia, indicating a potential safety concern with IV administration, while overall survival and locoregional control were similar between both treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late follow-up of the randomized radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) trial for advanced head and neck cancer. Heukelom, J., Lopez-Yurda, M., Balm, AJ., et al.[2018]

In a study of 4520 patients with stage III to IVb head and neck squamous cell carcinoma, those treated with cisplatin alongside radiation therapy had significantly better overall survival compared to those treated with cetuximab, with a median survival of 4.1 years versus 1.7 years for cetuximab.

After adjusting for treatment biases, cetuximab continued to show inferior overall survival rates, suggesting that cisplatin is a more effective partner for radiation therapy in the nonoperative management of this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab with definitive concurrent radiotherapy for head and neck squamous cell carcinoma: An analysis of Veterans Health Affairs data. Bauml, JM., Vinnakota, R., Anna Park, YH., et al.[2023]

Combined treatment of radiotherapy with cisplatin and etoposide has shown significant improvements in local control and survival rates for patients with locally advanced non-small cell lung cancer (NSCLC), with median survival rates reported between 15-18 months and 2-year survival rates around 35-40%.

Recent advancements in radiation technology and the use of third-generation chemotherapy drugs have led to promising results, including median survival exceeding 20 months, although careful management of treatment to minimize toxicity, particularly esophageal toxicity, remains crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data. Reboul, FL.[2019]

Patients with oropharyngeal carcinoma (OPC) treated with intensity-modulated proton therapy (IMPT) experienced significantly lower rates of acute toxic effects compared to those treated with intensity-modulated radiation therapy (IMRT), including less oral pain, xerostomia, and dysphagia.

Despite the reduced toxicity, both IMPT and IMRT showed similar oncologic outcomes, with 3-year overall survival rates of 97% for IMPT and 91% for IMRT, indicating that IMPT is a safer option without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Oropharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy. Youssef, I., Yoon, J., Mohamed, N., et al.[2023]

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