Radiation, Cisplatin, and Surgery for Throat Cancer

(MINT-2 Trial)

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines different treatment approaches for throat cancer linked to HPV, a common virus. The goal is to reduce side effects while preventing cancer recurrence. Participants will undergo surgery to remove the tumor, followed by radiation therapy. Some participants will also receive Cisplatin, a chemotherapy drug, depending on their cancer type. Individuals diagnosed with HPV-related throat cancer and planning surgery might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Studies have shown that combining cisplatin with radiation therapy is generally well-tolerated for head and neck cancers. Research comparing different cisplatin dosing schedules found similar safety levels among patients. Common side effects include nausea, low blood counts, and kidney issues, but supportive care can often manage these.

Radiation therapy alone is also commonly used and considered safe. It may cause side effects like skin irritation or tiredness, but these usually subside after treatment ends.

In summary, both treatments have been used in similar conditions and are known to be safe, though some side effects might occur. Always discuss potential risks and benefits with your doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for throat cancer because they are exploring different combinations and intensities of radiation and chemotherapy to improve outcomes. Unlike the traditional approach, which typically involves a standard radiation dose, these experimental treatments vary the dose and include cisplatin, a chemotherapy drug, in some arms to potentially enhance effectiveness. This trial specifically investigates how adjusting radiation doses and adding cisplatin can target cancer cells more precisely, which could lead to better management of the disease and potentially fewer side effects. By tailoring the radiation and incorporating cisplatin strategically, the hope is to find a more effective protocol that could become a new standard of care.

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

In this trial, participants will receive different treatment combinations to evaluate their effectiveness for throat cancer. Research has shown that combining radiation therapy with the drug Cisplatin, which some participants may receive, effectively treats certain head and neck cancers. Studies have found that this combination contains the cancer in its original area 97% of the time and prevents it from worsening in 88% of cases. Together, radiation and Cisplatin help extend life and prevent the cancer from spreading. This combination is especially recommended for treating HPV-related throat cancer, particularly in more severe cases, as it targets cancer cells more effectively than radiation alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Douglas R. Adkins

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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

Receiving any other investigational agents

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

I have had radiation therapy for head and neck cancer.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10709267/

Treatment outcomes of radiotherapy with concurrent ... Tri-weekly cisplatin and radiotherapy (CDDP + RT) is a standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) ...

2. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2788326

Elective Radiotherapy Dose and Field in HPV-Associated ... The 24-month locoregional control was 97.0%; progression-free survival, 88.0%; distant metastasis–free survival, 95.2%; and overall survival, ...

3. practicalradonc.org practicalradonc.org/article/S1879-8500(24)00139-5/fulltext

Radiation Therapy for HPV-Positive Oropharyngeal ... Concurrent cisplatin is recommended for patients receiving definitive RT with T3-4 disease and/or 1 node >3 cm, or multiple nodes. For similar ...

4. mdpi.com mdpi.com/2072-6694/16/12/2228

Audiological Outcomes of Weekly vs. Triweekly Cisplatin in ... Recent data from randomized phase 3 studies showed that weekly cisplatin has the same oncological outcomes as high-dose triweekly cisplatin when combined with ...

5. medicaljournalssweden.se medicaljournalssweden.se/actaoncologica/article/download/26800/31530/79417

Cisplatin and Radiotherapy in the Treatment of Locally ... Radiotherapy alone has an impact on the short-term prognosis of advanced head and neck cancer but the long-term benefits have been moderate (2, 3). The majority ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11513364/

Retrospective study of cisplatin plus radiotherapy toxicities ... Weekly cisplatin plus radiation for postoperative head and neck cancer (JCOG1008): A multicenter, noninferiority, Phase II/III randomized ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2772906025000263

Review Article Comparing efficacy and safety of weekly vs. ... Both weekly and triweekly cisplatin regimens show comparable survival outcomes and safety profiles in patients with head and neck cancers, except for short term ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01953952

Radiation Therapy and Cisplatin With or Without Surgery in ... This randomized phase II trial studies radiation therapy and cisplatin with or without surgery in treating patients with stage III-IV oropharyngeal cancer.

9. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2827612

Weekly Cisplatin Cycles and Outcomes for Chemoradiation ... These findings suggest that missing several cycles of weekly cisplatin is associated with worse survival, even among those with p16-negative tumors.

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.01293

Weekly Cisplatin Plus Radiation for Postoperative Head ... Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN.