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

Trial Summary

What is the purpose of this trial?

This is a prospective, phase II, stratified single arm investigation for favorable prognosis in p16+ oropharynx cancer patients with either node negative or malignant neck adenopathy with lymphoscintigraphy mapping confined to the ipsilateral neck.

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.

What data supports the effectiveness of the treatment Neck Radiation +/− Cisplatin for Oropharyngeal Cancer?

Research shows that adding cisplatin to radiation therapy improves outcomes for head and neck cancers, including better overall survival and tumor response rates. Cisplatin-based chemoradiation is considered the standard treatment for advanced head and neck cancers. ^{1 2 3 4 5}

Is the combination of neck radiation and cisplatin generally safe for humans?

The combination of neck radiation and cisplatin is generally considered safe, but it can cause significant side effects. Modern radiation techniques like IMRT and IMPT aim to reduce these side effects by better targeting the tumor and sparing healthy tissue. However, patients may still experience toxic effects, and the addition of cisplatin can increase toxicity to normal tissues. ^{6 7 8 9 10}

How is the treatment of neck radiation with or without cisplatin for oropharyngeal cancer different from other treatments?

This treatment combines neck radiation with or without cisplatin, a chemotherapy drug known for its high tumor response rate, specifically targeting oropharyngeal cancer. The use of intensity-modulated radiotherapy (IMRT) allows precise targeting of the cancer, potentially reducing side effects compared to traditional radiation methods. ^{1 3 4 5 11}

Research Team

Thomas Galloway, MD

Principal Investigator

Fox Chase Cancer Center

Eligibility Criteria

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

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

My blood, kidney, and liver tests are normal.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. India pubmed.ncbi.nlm.nih.gov

Carboplatin-based concurrent chemoradiation therapy in locally advanced head and neck cancer patients who are unfit for cisplatin therapy. [2018]

2. United States 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. [2023]

3. 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]

4. Japan pubmed.ncbi.nlm.nih.gov

Selective intraarterial chemoradiation therapy for oropharyngeal carcinoma with high-dose cisplatin. [2021]

5. United States 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. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Current strategies in radiotherapy of head and neck cancer. [2021]

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

Advances in radiation oncology for the management of oropharyngeal tumors. [2018]

8. United States 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. [2018]

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

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

10. United States 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. [2023]

11. Ireland 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. [2019]