Radiation Therapy + Cisplatin for Head and Neck Cancer

Recruiting at 218 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ECOG-ACRIN Cancer Research Group

Disqualifiers: Recurrent disease, Multiple primaries, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

189 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether radiation therapy alone or combined with cisplatin is more effective for treating head and neck cancer. Radiation therapy uses high-energy x-rays to kill cancer cells, while cisplatin, a chemotherapy drug, stops cancer cells from growing or spreading. Participants will receive either radiation therapy alone or in combination with cisplatin. Individuals who have undergone surgery for stage III-IVA squamous cell carcinoma of the head and neck, and whose cancer is not HPV-related, 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?

Research has shown that Intensity-Modulated Radiation Therapy (IMRT) is generally safe for treating head and neck cancer. It precisely targets tumors, reducing long-term side effects. Patients often experience fewer problems compared to older radiation methods.

When adding the drug cisplatin to IMRT, studies have found that both weekly and every-three-week dosing schedules are effective and similarly safe. Although cisplatin can cause side effects like hearing loss, smaller, more frequent doses may help reduce these effects. Overall, both IMRT alone and with cisplatin have been well-tolerated in previous studies, providing strong evidence of their safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they combine intensity-modulated radiation therapy (IMRT) with or without the addition of cisplatin, a chemotherapy drug. Unlike standard treatments, which often use traditional radiation therapy methods, IMRT is highly precise, targeting tumors more accurately while minimizing damage to surrounding healthy tissue. The addition of cisplatin in one of the trial arms aims to enhance the effectiveness of the radiation by making cancer cells more sensitive to it. This combination could potentially improve outcomes for patients by boosting the therapy's impact while reducing side effects.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

This trial will compare two treatment approaches for head and neck cancer. Participants in one arm will receive Intensity-Modulated Radiation Therapy (IMRT) alone. Studies have shown that IMRT precisely targets tumors with high doses of radiation while reducing damage to nearby healthy tissue, minimizing side effects like severe dry mouth. In another arm, participants will receive both IMRT and cisplatin. Research indicates that combining these treatments can improve survival rates. Cisplatin, a chemotherapy drug, stops cancer cells from growing and dividing. Studies show that using cisplatin with radiation therapy can enhance the treatment's effectiveness against cancer. Both treatment approaches in this trial have demonstrated positive outcomes in previous studies, suggesting they can effectively manage head and neck cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Robert Ferris

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with stage III-IVA squamous cell carcinoma of the head and neck who've had surgery. They should not have recurrent disease or multiple cancers, must be two years free from other cured cancers (except certain skin/cervix cancers), and can't have had prior radiation in the same area. Participants need proper kidney function, blood counts within normal ranges, no pregnancy or breastfeeding, and they must use contraception.

Inclusion Criteria

Your platelet count is at least 100,000 per cubic millimeter within 4 weeks before starting the study.

Patient must meet all eligibility criteria outlined in pre-registration before randomization

Women must not be pregnant or breast-feeding; females of childbearing potential must have a blood or urine study within 2 weeks prior to randomization to rule out pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo intensity-modulated radiation therapy (IMRT) once daily 5 days a week for 6 weeks. In Arm B, participants also receive cisplatin intravenously weekly for 6 weeks.

6 weeks

Follow-up

Participants are monitored for disease-free survival and adverse events every 6 months for 3 years, then annually for 7 years.

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Intensity-Modulated Radiation Therapy

Trial Overview

The study is examining if adding cisplatin to radiation therapy improves outcomes for patients post-surgery compared to radiation alone. It's a phase II trial where participants are randomly assigned to receive either both treatments or just radiation therapy.

How Is the Trial Designed?

Group I: Arm B (IMRT, cisplatin) Experimental Treatment 3 Interventions

Patients undergo IMRT QD 5 days a week and receive cisplatin IV over 1-2 hours weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (IMRT) Experimental Treatment 2 Interventions

Patients undergo IMRT QD 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.

Intensity-Modulated Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as IMRT for:

• Oropharyngeal cancer
• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer

Approved in European Union as IMRT for:

• Oropharyngeal cancer
• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer

Approved in Canada as IMRT for:

• Oropharyngeal cancer
• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Whole-field sequential intensity-modulated radiotherapy (WF S-IMRT) for patients with local-regional advanced head-and-neck squamous cell carcinoma showed excellent treatment outcomes, with 2-year overall survival rates at 94% and 5-year rates at 77% based on a study of 103 patients.

The treatment had an acceptable safety profile, with significant acute adverse events like mucositis and dysphagia occurring in some patients, but no severe grade 4 adverse events were reported, indicating that WF S-IMRT is a safe option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-Field Sequential Intensity-Modulated Radiotherapy for Local-Regional Advanced Head-and-Neck Squamous Cell Carcinoma. Refaat, T., Choi, M., Thomas, TO., et al.[2022]

In a study of 20 patients undergoing intensity-modulated radiotherapy (IMRT) for head and neck cancer, acute side effects were common, with 19 patients experiencing xerostomia (dry mouth) and 18 reporting mucositis (inflammation of the mucous membranes).

Long-term effects included persistent xerostomia in 11 out of 14 patients and an increase in trismus (restricted jaw movement) in 4 patients, indicating that while some acute symptoms improved, certain complications remained significant after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral complications of head and neck radiotherapy: prevalence and management. Germano, F., Melone, P., Testi, D., et al.[2017]

In a study of 57 patients with advanced head and neck cancer, the combination of intensity-modulated radiotherapy (IMRT) and weekly cisplatin chemotherapy resulted in high in-field tumor control (89.1%) and overall survival rates (86.9%) over a 2-year period.

The treatment was found to be feasible and generally well tolerated, with a median radiation dose of 70 Gy and a mean cisplatin dose of 25.7 mg/m² per week, indicating a promising approach for managing locoregionally advanced head and neck squamous cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive IMRT plus weekly cisplatin for advanced head and neck cancer: the University of Wisconsin experience. Traynor, AM., Richards, GM., Hartig, GK., et al.[2021]

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]

In a study of 3172 patients with head and neck cancers, those treated with intensity-modulated radiation therapy (IMRT) showed a significant improvement in cause-specific survival (CSS) at 84.1% compared to 66.0% for those treated with non-IMRT methods, over a median follow-up of 40 months.

The analysis indicated that IMRT not only reduces toxicity but also enhances cancer outcomes, as all subgroups analyzed demonstrated better CSS with IMRT compared to non-IMRT treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved survival using intensity-modulated radiation therapy in head and neck cancers: a SEER-Medicare analysis. Beadle, BM., Liao, KP., Elting, LS., et al.[2022]

In a study of 18 patients with head and neck cancer treated with intensity-modulated radiotherapy (IMRT), a high overall response rate was observed, with 71.4% achieving a complete or partial response at 3 months, increasing to 89% at a median follow-up of 5.6 months.

Concurrent chemotherapy with IMRT was well-tolerated, with no distant metastasis reported, suggesting that this treatment combination may be effective and safe for patients with locoregionally advanced head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy in head-and-neck cancer, first report in Thailand. Lertbutsayanukul, C., Khorprasert, C., Shotelersuk, K., et al.[2016]

A study involving 36 patients with locally advanced unresectable head and neck cancer showed that moderately accelerated intensity-modulated radiation therapy (IMRT) combined with weekly cisplatin after induction chemotherapy is feasible and resulted in a 63.8% complete response rate.

Despite the promising efficacy, the treatment was associated with significant toxicity, including a 30.5% incidence of Grade III mucositis and a 5.5% early death rate, highlighting the need for improved supportive care to manage these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study of moderately accelerated intensity-modulated radiotherapy plus concurrent weekly cisplatin after induction chemotherapy in locally advanced head-and neck cancer. Morganti, AG., Mignogna, S., Deodato, F., et al.[2013]

In a study of 60 patients with locally advanced head and neck squamous cell carcinoma (HNSCC), weekly low-dose cisplatin (30 mg/m2) resulted in significantly lower acute toxicities compared to high-dose cisplatin (100 mg/m2 every 3 weeks), with 56.6% of patients experiencing severe side effects versus 76.6% in the high-dose group.

While the low-dose regimen had better patient compliance (70% completing at least 6 doses) and lower toxicity, it also resulted in a lower loco-regional control rate (57.6%) compared to the high-dose group (72.8%), indicating a trade-off between safety and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin Weekly Versus Every 3 Weeks Concurrently with Radiotherapy in the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinomas: What Is the Best Dosing and Schedule? Mashhour, K., Hashem, W.[2020]

In a study of 38 head and neck cancer patients treated with a specific radiotherapy protocol (SIB-IMRT), no patients experienced severe grade 4 toxicity, indicating that the treatment is safe and well-tolerated.

While all patients completed the therapy without interruption, those receiving concurrent chemotherapy experienced more severe acute toxicity, suggesting that while chemotherapy may enhance treatment effectiveness, it also increases the risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMRT with the use of simultaneous integrated boost in treatment of head and neck cancer: acute toxicity evaluation. Vosmik, M., Odrázka, K., Dolezel, M., et al.[2016]

In a study of 100 patients treated with intensity-modulated radiotherapy (IMRT) for head and neck cancer, the 3-year overall survival rate was 71%, indicating that IMRT is an effective treatment option.

While IMRT showed promising outcomes, there were cases of local failure at the edges of high-dose areas, suggesting that careful planning is crucial to avoid recurrence in these regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of failure and toxicity after intensity-modulated radiotherapy for head and neck cancer. Schoenfeld, GO., Amdur, RJ., Morris, CG., et al.[2022]

In a study of 45 patients with stage III/IV head and neck squamous cell carcinomas treated with intensity-modulated radiotherapy (IMRT) and weekly cisplatin, the two-year loco-regional recurrence-free survival rate was 85.4%, indicating strong efficacy in controlling the disease.

The treatment regimen, which included a total dose of 7000 cGy delivered in 35 fractions along with a median of 6 cycles of cisplatin, resulted in an overall survival rate of 87.4% over a median follow-up of 28 months, demonstrating the potential effectiveness of this combined approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy using simultaneous-integrated boost for definitive treatment of locally advanced mucosal head and neck cancer: outcomes from a single-institution series. Johnston, M., Guo, L., Back, M., et al.[2019]

Intensity-modulated radiotherapy (IMRT) has shown high effectiveness in treating head-and-neck squamous cell carcinoma, with a 2-year overall survival rate of 85% and a local progression-free survival rate of 94% based on a study of 150 patients.

Patients with oropharyngeal cancer had significantly better outcomes compared to those with oral cavity and laryngeal cancers, indicating that cancer site plays a crucial role in treatment success, with a local-regional control rate of 98% for oropharyngeal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation treatment for head-and-neck squamous cell carcinoma--the University of Iowa experience. Yao, M., Dornfeld, KJ., Buatti, JM., et al.[2013]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

Weekly Cisplatin Cycles and Outcomes for Chemoradiation ...

To address this knowledge gap, we performed an observational cohort study of patients with head and neck cancer who underwent definitive ...

2.

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 ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12071001/

Comparison of Weekly and Triweekly Cisplatin Regimens ...

Overall, both schedules appear to be equally effective and safe. Our findings indicate that the treatment plan should be based on the individual ...

4.

thegreenjournal.com

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

Predicting cisplatin tolerability in older adults with head ...

Cumulative cisplatin doses of ≥ 200 mg/m2 improve survival in adults with head-and-neck squamous cell carcinoma (HNSCC) undergoing chemoradiation, ...

5.

ascopubs.org

ascopubs.org/doi/full/10.1200/jco.22.00274

For Head and Neck Cancer, It Is Still Cisplatin, But How ...

Reported treatment benefits of adjuvant radiation were large, estimated at 30%-50% in relative overall survival, on the basis of larger series ...

6.

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.

7.

insight.jci.org

insight.jci.org/articles/view/196230

Lower, more frequent cisplatin dosing minimizes hearing ...

Cisplatin-induced ototoxicity is dose dependent, often more severe with higher cumulative doses, and can significantly impact quality of life ...