Radiation Therapy + Cisplatin for Head and Neck Cancer

Recruiting at208 trial locations

Overseen by Robert Ferris

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: ECOG-ACRIN Cancer Research Group

Disqualifiers: Recurrent disease, Multiple primaries, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is studying if using a specific type of energy treatment alone or with a drug is better for treating patients with advanced head and neck cancer after surgery. The energy treatment kills cancer cells, and the drug helps by stopping their growth or killing them. The drug has been used for many years in the treatment of advanced cancers, including head and neck cancers, and is known for its ability to enhance the effects of the energy treatment.

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 Radiation Therapy + Cisplatin for Head and Neck Cancer?

Research shows that using intensity-modulated radiation therapy (IMRT) for head and neck cancer can improve survival rates and reduce side effects compared to older methods. Additionally, combining IMRT with cisplatin, a chemotherapy drug, has been studied for its effectiveness in controlling tumors and improving patient outcomes. ^{1 2 3 4 5}

Is the combination of radiation therapy and cisplatin generally safe for treating head and neck cancer?

The combination of radiation therapy and cisplatin for head and neck cancer has been studied, and while it can cause side effects, it is generally considered to have an acceptable safety profile. Some patients may experience more severe side effects when chemotherapy is added, but most complete the treatment without needing to stop due to these effects. ^{3 6 7 8 9}

How is the treatment of Radiation Therapy + Cisplatin for Head and Neck Cancer different from other treatments?

This treatment uses Intensity-Modulated Radiation Therapy (IMRT), which allows for more precise targeting of the tumor while sparing healthy tissue, potentially reducing side effects compared to conventional radiation therapy. Cisplatin, a chemotherapy drug, is used alongside IMRT to enhance the treatment's effectiveness. ^{3 5 10 11 12}

Research Team

Robert Ferris

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

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

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

Trial Timeline

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

Treatment Details

Interventions

• Cisplatin (Alkylating agents)
• Intensity-Modulated Radiation Therapy (Radiation)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Peter J. O'Dwyer

ECOG-ACRIN Cancer Research Group

Chief Executive Officer since 2012

MD from University of Pennsylvania

Dr. Mitchell D. Schnall

ECOG-ACRIN Cancer Research Group

Chief Medical Officer since 2012

MD, PhD from University of Pennsylvania

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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 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 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 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 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 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 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]

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 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 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]

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]

References

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

Patterns of failure and toxicity after intensity-modulated radiotherapy for head and neck cancer. [2022]

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

Improved survival using intensity-modulated radiation therapy in head and neck cancers: a SEER-Medicare analysis. [2022]

3. Thailand 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? [2020]

4. Thailand pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy in head-and-neck cancer, first report in Thailand. [2016]

5. United States 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. [2013]

6. Italy pubmed.ncbi.nlm.nih.gov

Oral complications of head and neck radiotherapy: prevalence and management. [2017]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

IMRT with the use of simultaneous integrated boost in treatment of head and neck cancer: acute toxicity evaluation. [2016]

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

Comprehensive IMRT plus weekly cisplatin for advanced head and neck cancer: the University of Wisconsin experience. [2021]

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

Whole-Field Sequential Intensity-Modulated Radiotherapy for Local-Regional Advanced Head-and-Neck Squamous Cell Carcinoma. [2022]

10. Australia 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. [2019]

11. Germany pubmed.ncbi.nlm.nih.gov

Current strategies in radiotherapy of head and neck cancer. [2021]

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

Intensity-modulated radiation treatment for head-and-neck squamous cell carcinoma--the University of Iowa experience. [2013]