Risk-Directed Therapy After Surgery for Throat Cancer

(MINT Trial)

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

63 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 after surgery for throat cancer?

Research shows that postoperative radiation therapy can improve local control of cancer in the throat area, although it may not significantly impact overall survival. This suggests that combining surgery with radiation might help reduce the chance of cancer coming back in the treated area. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The research articles focus on outcomes and complications related to head and neck surgery and radiotherapy, but they do not provide specific safety data for the treatments like Cisplatin or Intensity Modulated Proton Therapy. However, these treatments have been used in various conditions, and their safety profiles are generally well-documented in medical literature. ^{6 7 8 9 10}

How does the treatment 'Risk-Directed Therapy After Surgery for Throat Cancer' differ from other treatments for this condition?

This treatment is unique because it involves tailoring post-surgery therapy based on individual risk factors, potentially combining surgery with radiation or chemotherapy to improve outcomes, especially for high-risk patients. Traditional treatments often use a one-size-fits-all approach, whereas this method aims to optimize therapy based on specific patient needs and risk profiles. ^{11 12 13 14 15}

What is the purpose of this trial?

The overarching goal of the MINT trial is to reduce treatment-related toxicity while maintaining efficacy. Patients with HPV-related oropharyngeal squamous cell carcinoma (OPSCC) will undergo resection of the primary tumor site and involved/at risk regional neck nodes.

Research Team

Douglas R. Adkins

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. [2019]

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

Risk of Recurrence in Laryngeal Cancer. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Total laryngectomy and T3-T4 laryngeal cancer without other adverse histopathology. [2007]

4. England pubmed.ncbi.nlm.nih.gov

Improved survival in patients with head and neck cancer in the 1990s. [2019]

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

Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial. [2019]

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

Above and Beyond Age: Prediction of Major Postoperative Adverse Events in Head and Neck Surgery. [2023]

7. England 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. [2022]

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

Systematic review of postoperative therapy for resected squamous cell carcinoma of the head and neck: Executive summary of the American Radium Society appropriate use criteria. [2021]

9. England pubmed.ncbi.nlm.nih.gov

A national analysis of the outcome of major head and neck cancer surgery: implications for surgeon-level data publication. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Patient-reported quality-of-life outcomes in relation to provider-assessed adverse events during head and neck radiotherapy. [2020]

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

Adjuvant chemotherapy of head and neck cancer: the past, the present, and the future. [2018]

12. England pubmed.ncbi.nlm.nih.gov

ACR appropriateness criteria® adjuvant therapy for resected squamous cell carcinoma of the head and neck. [2014]

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

Postoperative chemoradiotherapy for advanced squamous cell carcinoma of the head and neck: a systematic review with meta-analysis. [2018]

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

Postoperative radiotherapy for squamous cell carcinoma of the head and neck. [2019]

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

Radiation following surgery for oral cancer: impact on local control. [2006]