Risk-Directed Therapy After Surgery for Throat Cancer

(MINT Trial)

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: Prior HNSCC therapy, Metastatic disease, 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: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatments for throat cancer linked to HPV, a common virus, following surgery. The goal is to find treatments that are equally effective but cause fewer side effects. Participants will undergo surgery to remove the tumor, followed by various combinations of radiation and chemotherapy, based on specific cancer characteristics. Ideal candidates have HPV-related throat cancer that can be surgically removed through the mouth. As a Phase 2 trial, the research focuses on measuring 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?

Research shows that cisplatin, a common chemotherapy drug, is generally safe but can cause some side effects. In a study of patients receiving cisplatin with radiation, most experienced side effects. Despite this, the drug remains widely used because it improves survival rates in head and neck cancers.

Intensity modulated proton therapy (IMPT) offers another treatment option. Studies indicate that IMPT can cause fewer side effects than traditional radiation methods. It targets cancer cells more precisely, protecting healthy tissues.

Both treatments address similar conditions, and while side effects are possible, they are considered safe for many patients. Patients should always discuss any concerns with their medical team to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they tailor post-operative care based on the patient's specific throat cancer characteristics. Unlike the traditional one-size-fits-all approach, these treatments use a risk-directed strategy to administer modified radiation and chemoradiation therapy. For patients with certain risk factors, such as extracapsular extension or positive margins, the treatment includes a combination of radiation and a targeted dose of cisplatin, which aims to enhance effectiveness while potentially reducing unnecessary exposure to chemotherapy. This personalized approach is expected to improve outcomes by precisely targeting the cancer cells, minimizing side effects, and optimizing recovery.

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

This trial will compare different post-operative treatments for throat cancer. Research has shown that surgery followed by radiation therapy, often with the drug cisplatin, effectively treats throat cancer. In this trial, some participants will receive post-operative adjuvant modified chemoradiation therapy (POAmCRT) with cisplatin, while others will receive post-operative adjuvant modified radiation therapy (POAmRT) without cisplatin. Studies indicate that high doses of cisplatin, when combined with radiation, can improve survival rates and help prevent cancer from spreading. Patients must receive the planned dose of cisplatin and be monitored for side effects. Intensity-modulated proton therapy (IMPT) precisely targets tumors while protecting healthy tissues, reducing side effects compared to traditional radiation. Both IMPT and IMRT (intensity-modulated radiation therapy) effectively control cancer in the treated area, with the added benefit of potentially fewer side effects, especially for the mouth and throat. These treatments aim to fight cancer effectively while minimizing harm to the rest of the body. ^{1 2 4 6 7}

Who Is on the Research Team?

Douglas R. Adkins

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

The MINT trial is for adults with HPV-related oropharyngeal squamous cell carcinoma stages I-III, who can undergo surgery via a transoral approach. Participants must have proper kidney function, no recent invasive cancers (with some exceptions), and not be pregnant. They should agree to use contraception and have an ECOG Performance Status of 0-2.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

My cancer is HPV-related and in stages I-III or is in the neck node with an unknown primary source.

My tumor will be removed through my mouth.

Exclusion Criteria

I was diagnosed with another cancer besides the one being studied within the last 2 years.

I have had treatment aimed at curing head and neck cancer.

My cancer has spread to distant parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Standard of care surgery involving resection of the primary tumor and management of cervical lymph nodes

1 week

1 visit (in-person)

Post-operative Adjuvant Therapy

Participants receive post-operative adjuvant therapy, including radiation and possibly chemoradiation, depending on risk factors

4-6 weeks

Weekly visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Multiple visits at 6 weeks, 4 months, 6 months, and 12 months post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Intensity modulated proton therapy
• Surgery

Trial Overview This trial tests post-operative therapy tailored to individual risk after surgical tumor removal in patients with HPV-related oral cancer. It aims to minimize treatment side effects while maintaining effectiveness, using various assessments and therapies including Cisplatin and radiation.

How Is the Trial Designed?

Group I: Arm 3: POACRT Experimental Treatment 9 Interventions

* Patients with clinical or pathologic T4 or clinical N3 disease * Standard of care surgery (surgical resection of the primary tumor via a transoral approach and surgical management of cervical lymph nodes * Treated with post-operative adjuvant chemoradiation therapy (POACRT) which is 60 Gy radiation therapy in 30 doses and 3 doses of cisplatin (if there is pathologic evidence of ECE or positive margins) * The first dose of cisplatin will given on one of the days during the initial 5 days of radiation therapy, the 2nd dose on the day of radiation dose 16, and the 3rd dose on the day of radiation dose 26. * It is recommended that radiation therapy begin within 28-49 days (no later than 56 days) after surgical resection * Intensity modulated radiation therapy (IMRT) or intensity modulated proton therapy (IMPT) is to be used for this study

Group II: Arm 2: POAmRT Experimental Treatment 8 Interventions

* Patients with no extracapsular extension (ECE) and no positive margins and not clinical or pathologic T4 or clinical N3 disease * Standard of care surgery (surgical resection of the primary tumor via a transoral approach and surgical management of cervical lymph nodes * Treated with post-operative adjuvant modified radiation therapy (POAmRT) which is 42 Gy radiation therapy in 21 doses * It is recommended that radiation therapy begin within 28-49 days (no later than 56 days) after surgical resection * Intensity modulated radiation therapy (IMRT) or intensity modulated proton therapy (IMPT) is to be used for this study

Group III: Arm 1: POAmCRT Experimental Treatment 9 Interventions

* Patients with extracapsular extension (ECE) or positive margin but not clinical or pathologic T4 or clinical N3 disease * Standard of care surgery (surgical resection of the primary tumor via a transoral approach and surgical management of cervical lymph nodes * Treated with post-operative adjuvant modified chemoradiation therapy (POAmCRT) which is 42 Gy radiation therapy in 21 doses and 1 dose of cisplatin. * It is recommended that radiation therapy begin within 28-49 days (no later than 56 days) after surgical resection * Intensity modulated radiation therapy (IMRT) or intensity modulated proton therapy (IMPT) is to be used for this study

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

A national analysis of 17,623 major head and neck cancer surgeries revealed a 3.5% in-hospital mortality rate, with significant risks associated with complications; the risk of death increased from 1.1% with no complications to 15.1% with two potentially lethal complications.

Patients with pharyngolaryngeal malignancies faced greater morbidity and a higher likelihood of emergency surgeries, highlighting the need for tailored stratification strategies to improve surgical outcomes and quality assurance in head and neck cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A stratified analysis of the perioperative outcome of 17623 patients undergoing major head and neck cancer surgery in England over 10 years: Towards an Informatics-based Outcomes Surveillance Framework. Nouraei, SA., Mace, AD., Middleton, SE., et al.[2022]

Postoperative radiotherapy (RT) significantly reduces the risk of local-regional recurrence in patients with squamous cell carcinoma of the head and neck, particularly those with unfavorable pathologic features.

High-risk patients may benefit from more aggressive RT schedules and adjuvant cisplatin-based chemotherapy, which can improve survival rates and the probability of cure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative radiotherapy for squamous cell carcinoma of the head and neck. Mendenhall, WM., Hinerman, RW., Amdur, RJ., et al.[2019]

A study of 3,455 patients with squamous cell carcinoma of the head and neck showed a significant improvement in 5-year tumor-specific survival rates from 50% before 1990 to 60% after 1990, indicating better treatment outcomes over time.

The reduction in neck node recurrence rates from 15% to 12% since 1990 is a key factor contributing to the improved survival rates, suggesting advancements in treatment strategies, possibly including more effective postoperative radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved survival in patients with head and neck cancer in the 1990s. Jones, AS., Houghton, DJ., Beasley, NJ., et al.[2019]

In a study analyzing 43,701 head and neck surgeries, 11.7% of patients experienced major postoperative adverse events (MPAEs), with factors like prolonged surgery, anemia, and free tissue transfer being the most predictive of these events.

Age was found to have a minimal impact on predicting MPAEs, contributing only 0.6% to 4.3% to the risk, while factors such as ASA class and hypertension had much larger attributable fractions, indicating that surgical and comorbid conditions are more critical in assessing risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Above and Beyond Age: Prediction of Major Postoperative Adverse Events in Head and Neck Surgery. Mascarella, MA., Muthukrishnan, N., Maleki, F., et al.[2023]

In a study of 65 patients undergoing head-and-neck radiotherapy, those with higher-grade adverse events reported significantly worse quality-of-life outcomes, particularly in areas like fatigue and overall well-being, especially at the beginning of treatment.

As treatment progressed, the negative impact of adverse events on quality of life appeared to decrease, suggesting that patients may adapt over time, and highlighting the importance of considering both patient-reported outcomes and provider-assessed adverse events for a comprehensive understanding of treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported quality-of-life outcomes in relation to provider-assessed adverse events during head and neck radiotherapy. Niska, JR., Thorpe, CS., Halyard, MY., et al.[2020]

Citations

1. 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.

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

Retrospective study of cisplatin plus radiotherapy toxicities ... A total of 274 (84%) patients were compliant and received the planned dose of cisplatin. Overall, 957 adverse events were reported in 98.2% of ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0385814625000732

Efficacy and safety of definitive low-dose weekly cisplatin ... The 2- and 5-year overall survival (OS) rates were 81.0% and 63.5%, respectively, with a complete response rate of 89.7%. A cumulative cisplatin dose of ≥200 mg ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11629129/

Weekly Cisplatin Cycles and Outcomes for Chemoradiation ... The National Comprehensive Cancer Network guideline recommends high-dose cisplatin delivered every 3 weeks as a category 1, preferred concurrent ...

5. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)04359-7/fulltext

Predicting cisplatin tolerability in older adults with head ... 53 % of older HNSCC patients achieved ≥ 200 mg/m2 cisplatin during chemoradiation. •. Classic and AI-based models predicting ≥ 200 mg/m2 cumulative cisplatin ...

6. 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 ...

7. nature.com nature.com/articles/s44276-025-00164-z

Long-term outcomes of consecutive patients ... Outcomes of HPV-negative oropharyngeal cancer are dismal with 5-year overall survival (OS) of 27% to 38% [5, 11]. Recently, data from the Danish ...