Radiation, Cisplatin, and Surgery for Throat Cancer

(MINT-2 Trial)

Overseen By Douglas Adkins, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: Cirrhosis, Prior radiation, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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: 21

142 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment involving radiation, cisplatin, and surgery for throat cancer?

Research shows that adding cisplatin to radiation therapy improves outcomes for head and neck cancer compared to radiation alone, suggesting that this combination can be effective for throat cancer treatment. ^{1 2 3 4 5}

Is the combination of radiation, cisplatin, and surgery generally safe for treating throat cancer?

The combination of radiation and cisplatin, often used for head and neck cancers, can cause side effects like ototoxicity (hearing damage) and wound complications, especially with brachytherapy (a type of internal radiation). Careful planning and management are needed to minimize these risks. ^{3 6 7 8 9}

How does the treatment of radiation, cisplatin, and surgery for throat cancer differ from other treatments?

This treatment combines radiation therapy and cisplatin (a chemotherapy drug) with surgery, which is unique because it uses multiple approaches to improve outcomes. Cisplatin enhances the effects of radiation, and surgery helps remove the cancer, offering a comprehensive strategy compared to using radiation or chemotherapy alone. ^{2 3 10 11 12}

What is the purpose of this trial?

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer. Oropharynx SCC (OPSCC) is a common sub-type of HNSCC. Each year, 16,000 new cases of OPSCC are diagnosed in the USA. Most cases of OPSCC (\>90%) are caused by the human papillomavirus (HPV) and are often cured with current therapy. However, patients treated with surgery followed by postoperative adjuvant chemotherapy and radiation therapy (POA(C)RT) still experience substantial morbidity. In this highly curable disease, current clinical research interest is focused on investigation of de-escalated therapy, with the goal to reduce treatment-related adverse events (AEs) while maintaining a low recurrence rate. In this study, patients with HPV-related OPSCC will undergo resection of the primary tumor site and involved/at-risk regional neck nodes. Based on the pathology report, patients will be assigned to: * Arm 1 (de-POACRT-42 Gy) * Arm 2A (de-POART-42 Gy) * Arm 2B (de-POART-37.8 Gy) * Arm 2C (de-POACRT-30 Gy). All patients with high-risk pathology will be assigned to Arm 1 whereas patients with intermediate-risk pathology will be randomized (1:1:1) to Arm 2A, Arm 2B, or Arm 2C. Patients with highest-risk pathology and low-risk pathology will be removed from the trial after surgery and will be advised to pursue standard of care options.

Research Team

Douglas R. Adkins

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for individuals with a type of throat cancer called HPV-related oropharynx squamous cell carcinoma. Participants must have undergone surgery to remove the tumor and neck nodes. They are then assigned to different treatment groups based on their pathology reports, except those with the highest or lowest risk who will be advised on standard care.

Inclusion Criteria

I can take care of myself and perform daily activities.

My cancer is HPV-related, in the early stages, but not the earliest.

Ability to understand and willingness to sign an IRB approved written informed consent document

Exclusion Criteria

My cancer is in an early stage and has not spread to lymph nodes or other parts of my body.

Receiving any other investigational agents

I have had radiation therapy for head and neck cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Standard of care surgery to resect the primary tumor site and involved/at-risk regional neck nodes

1 week

Radiation Therapy

Radiation therapy begins within 28 to 49 days post-surgery, with varying doses based on assigned arm

3-4 weeks

21 visits (in-person)

Chemotherapy

Cisplatin administered on the same day as one of the initial 5 doses of radiation therapy for certain arms

Concurrent with radiation

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years and 10 weeks

Treatment Details

Interventions

• Cisplatin
• Radiation therapy
• Surgery

Trial Overview The study tests reduced-intensity treatments after surgery in patients with HPV-related throat cancer to see if they can lower side effects while keeping cancer from coming back. Patients receive varying doses of radiation and some get chemotherapy (Cisplatin), depending on their risk level determined by pathology results.

Participant Groups

Group I: Arm 2C: Radiation therapy + Cisplatin Experimental Treatment 3 Interventions

* Standard of care surgery will occur before adjuvant therapy. * It is recommended that radiation therapy begin within 28 to 49 days (and no later than 56 days). * The total dose to the postoperative tumor bed will be 3000 cGy in 15 fractions of 200 cGy over 3 weeks. * Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 2700 cGy in 15 fractions of 180 cGy each. * Cisplatin will be given on the same day as one of the initial 5 doses of radiation therapy.

Group II: Arm 2B: Radiation therapy Experimental Treatment 2 Interventions

* Standard of care surgery will occur before adjuvant therapy. * It is recommended that radiation therapy begin within 28 to 49 days (and no later than 56 days). * The total dose to the postoperative tumor bed will be 3780 cGY in 21 fractions of 180 cGy each over 4 weeks. * Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 3360 cGy in 21 fractions of 160 cGy each.

Group III: Arm 2A: Radiation therapy Experimental Treatment 2 Interventions

* Standard of care surgery will occur before adjuvant therapy. * It is recommended that radiation therapy begin within 28 to 49 days (and no later than 56 days). * The total dose to the postoperative tumor bed will be 4200 cGy in 21 fractions of 200 cGy each over 4 weeks. * Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 3780 cGy in 21 fractions of 180 cGy each.

Group IV: Arm 1: Radiation therapy + Cisplatin Experimental Treatment 3 Interventions

* Standard of care surgery will occur before adjuvant therapy. * It is recommended that radiation therapy begin within 28 to 49 days (and no later than 56 days). * The total dose to the postoperative tumor bed will be 4200 cGy in 21 fractions of 200 cGy each over 4 weeks. * Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 3780 cGy in 21 fractions of 180 cGy each. * Cisplatin will be given on the same day as one of the initial 5 doses of radiation therapy.

Radiation therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiotherapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer

Approved in United States as Radiation therapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer
• Cervical cancer
• Uterine cancer

Approved in Canada as Radiotherapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer

Approved in Japan as Radiation therapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer
• Esophageal cancer

Approved in China as Radiotherapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer
• Nasopharyngeal cancer

Approved in Switzerland as Radiation therapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

The Joseph Sanchez Foundation

Collaborator

Trials

2

Recruited

220+

Findings from Research

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]

Recent advances in radiotherapy for head and neck cancer include improved techniques like three-dimensional conformal treatment planning and charged particle irradiation, which enhance targeting of tumors while minimizing damage to surrounding healthy tissue.

The review highlights the importance of combining radiotherapy with other treatments, such as neoadjuvant chemotherapy, to improve outcomes like laryngeal preservation and the effectiveness of postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in radiotherapy for head and neck cancer. Mendenhall, WM., Parsons, JT., Buatti, JM., et al.[2019]

The study developed the Functional Assessment of Cancer Therapy-Head and Neck Radiotherapy (FACT-HN-RAD) measure, an 8-item tool that effectively captures the most common adverse effects (AEs) of radiation therapy in patients with head and neck squamous cell carcinoma, based on input from 19 patients and 9 radiation oncologists.

Common AEs identified include difficulty swallowing, oral pain, dry mouth, and weight loss, with the measure demonstrating strong face validity among patients, indicating it accurately reflects their experiences during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring Adverse Effects of Radiation Therapy in Patients With Head and Neck Cancer: The FACT-HN-RAD Patient-Reported Outcome Measure. Gharzai, LA., Mierzwa, ML., Peipert, JD., et al.[2023]

External beam radiation therapy is a common and effective treatment for head and neck cancers, which account for about 3% of all cancers in the U.S., with 62,000 new cases diagnosed each year.

Due to the complex anatomy of the head and neck region, careful planning of radiation therapy is crucial to minimize side effects on critical structures, and the review provides guidelines for managing these side effects and improving patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Radiation Toxicity in Head and Neck Cancers. Siddiqui, F., Movsas, B.[2018]

Proton therapy for head and neck cancer shows promising results by delivering a lower overall radiation dose while effectively targeting the tumor, which may lead to fewer side effects compared to conventional radiotherapy.

Despite the advantages of proton therapy, conventional radiotherapy remains a strong option due to the extensive research available, suggesting that careful planning and comparison of treatment methods are essential for optimal patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of meta-analysis approach, comparing conventional radiotherapy, and proton beam therapy treating head and neck cancer. Shaikh, F., Sodhi, SK., Kale, LM., et al.[2022]

References

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

Consensus Quality Measures and Dose Constraints for Head and Neck Cancer with an emphasis on Oropharyngeal and Laryngeal Cancer from the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Expert Panel. [2023]

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

Ototoxicity after combined platinum and fractionated radiation in a novel guinea pig model. [2018]

4. Greece pubmed.ncbi.nlm.nih.gov

Akt1 rs2498801 is related to survival in head and neck squamous cell cancer treated with radiotherapy. [2019]

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

Advances in radiotherapy for head and neck cancer. [2019]

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

Risk factors of ototoxicity after cisplatin-based chemo-irradiation in patients with locally advanced head-and-neck cancer: a multivariate analysis. [2015]

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

Monitoring Adverse Effects of Radiation Therapy in Patients With Head and Neck Cancer: The FACT-HN-RAD Patient-Reported Outcome Measure. [2023]

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

Wound complications associated with brachytherapy for primary or salvage treatment of head and neck cancer. [2019]

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

Management of Radiation Toxicity in Head and Neck Cancers. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Combination of chemotherapy with radiotherapy: review of previous studies and new perspectives. [2013]

11. India pubmed.ncbi.nlm.nih.gov

Concomitant cisplatin and radiationtherapy in advanced head and neck cancers:. [2021]

12. India pubmed.ncbi.nlm.nih.gov

Implementation of meta-analysis approach, comparing conventional radiotherapy, and proton beam therapy treating head and neck cancer. [2022]