Stereotactic Radiotherapy + Cisplatin for Head and Neck Cancer

Overseen By Jonathan Schoenfeld, MD MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Antiretrovirals, G-CSF, Bevacizumab, others

Disqualifiers: Pregnancy, HIV, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating head and neck cancer that has recurred or spread. It combines a focused "boost" dose of radiation, known as stereotactic body radiotherapy (SBRT), with the standard chemotherapy drug, cisplatin. The researchers aim to determine if this precise radiation can improve treatment outcomes. Suitable candidates are those with a history of head and neck cancer and tumors that cannot be surgically removed. Participants must have measurable tumors in the head or neck area. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain medications like granulocyte stimulating factor, bevacizumab, cyclosporine, anti-tumor necrosis factor agents, or amifostine. If you are HIV-positive and on antiretroviral therapy, you are not eligible for the trial.

What prior data suggests that stereotactic body radiotherapy and cisplatin are safe for treating head and neck cancer?

Research has shown that cisplatin, a chemotherapy drug for head and neck cancers, is generally well-tolerated by patients. Studies comparing weekly and every-three-week cisplatin treatments have found similar safety and effectiveness, indicating that patients experience side effects at similar rates regardless of the schedule.

For stereotactic body radiotherapy (SBRT), research indicates it is safe at standard doses. One study found no severe side effects that would halt treatment, suggesting it is manageable. SBRT has been tested in various situations, including treating recurring head and neck cancers, and it has demonstrated acceptable side effects.

In summary, both cisplatin and SBRT have been studied for safety in humans, and research supports their tolerability when used correctly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine innovative radiotherapy methods with chemotherapy to tackle head and neck cancer in a unique way. Unlike traditional treatments that often rely solely on standard radiation therapy, this approach uses Intensity Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiotherapy (SBRT) to deliver highly precise doses of radiation. This precision targets tumors more accurately, potentially reducing side effects and allowing for higher doses directly to the cancer cells. Additionally, combining these advanced radiotherapy techniques with Cisplatin, a well-known chemotherapy drug, aims to enhance the treatment's effectiveness, especially in patients who have received prior radiation or have metastatic tumors.

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

Research has shown that combining the drug cisplatin with radiation effectively treats head and neck cancer. In this trial, participants in Cohort 1 will receive Intensity Modulated Radiation Therapy (IMRT) daily for six weeks, with cisplatin administered intravenously on predetermined days. Studies have found that higher doses of cisplatin can extend patient survival, and using radiation with cisplatin has demonstrated significant benefits in overall survival.

Cohort 2 will receive Stereotactic Body Radiotherapy (SBRT), another promising treatment. It delivers radiation in a highly targeted manner, helping to control cancer and relieve symptoms. Research indicates that SBRT is safe and has manageable side effects, making it a good option for treating cancer that has returned or spread. ^{1 6 7 8 9}

Who Is on the Research Team?

Jonathan D. Schoenfeld, MD MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

Adults with recurrent or metastatic head and neck cancer, who have measurable disease in the region, can join this trial. They must not have other active cancers (except certain skin cancers or cervical carcinoma in situ), be medically fit for treatment, and have normal organ/marrow function. Pregnant women, individuals with large SBRT target sizes (>6 cm or >100 cc), those on specific medications like Bevacizumab or anti-tumor necrosis factor agents, and HIV-positive patients on antiretroviral therapy are excluded.

Inclusion Criteria

I haven't had any cancer except for skin cancer or cervical pre-cancer in the last 2 years.

I have a solid tumor in my head or neck that has spread and can be measured.

My cancer has been confirmed through lab tests.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

My treatment target is larger than 6 cm or more than 100 cc in volume.

I am scheduled to receive treatments like G-CSF or Bevacizumab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive stereotactic body radiotherapy (SBRT) and possibly a boost dose in combination with standard radiation and chemotherapy

6 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Intensity Modulated Radiation Therapy (IMRT)
• Stereotactic Body Radiotherapy (SBRT)

Trial Overview The study is testing whether adding a high-dose precision radiation 'boost' using Stereotactic Body Radiotherapy (SBRT) to standard treatments like Cisplatin chemotherapy and Intensity Modulated Radiation Therapy (IMRT) improves outcomes for patients with head and neck cancer that has returned or spread.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 1 Intervention

* Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. * Cohort 2 (patients with metastatic solid tumors of any histology who have targetable lesions within the head and neck) -- Stereotactic Body Radiotherapy (SBRT)

Group II: Cohort 1 Experimental Treatment 3 Interventions

* Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. * Cohort 1 (patients who have received prior radiation in the head and neck with gross unresectable disease) * Intensity Modulated Radiation Therapy (IMRT) : daily for 6 weeks * Cisplatin will be administered intravenously on predetermined days * Stereotactic Body Radiotherapy (SBRT)

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Published Research Related to This Trial

Stereotactic body radiotherapy (SBRT) is primarily used for recurrent head and neck cancer, with usage rates ranging from 10% to 100%, while it is rarely applied to newly diagnosed cases (0-10%).

There is significant variability in treatment techniques and patient selection among 15 international institutions, including differences in target volume margins and fractionation regimens, which may impact treatment outcomes and safety, such as the risk of carotid blowout ranging from 3% to 20% in re-irradiation cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey of current practices from the International Stereotactic Body Radiotherapy Consortium (ISBRTC) for head and neck cancers. Karam, I., Yao, M., Heron, DE., et al.[2018]

Stereotactic body radiotherapy (SBRT) at doses up to 44 Gy was found to be safe for previously irradiated patients with squamous cell carcinoma of the head and neck, with no severe toxicities reported and only mild acute side effects in four patients.

The treatment showed a 17% objective response rate, with some patients experiencing stable disease for up to 4 months, suggesting that SBRT could be a viable option for reirradiation in this patient population, warranting further studies alongside other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: results of a phase I dose-escalation trial. Heron, DE., Ferris, RL., Karamouzis, M., 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]

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]

Stereotactic radiotherapy (SBRT) shows promise in treating head and neck cancer (HNC), particularly in reirradiation settings, but there is currently insufficient evidence to support its use as a primary treatment option.

While SBRT carries risks such as carotid blow out syndrome, alternative treatment regimens may help mitigate these risks, highlighting the need for further research through large Phase III trials to establish its efficacy and safety in HNC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and practical considerations of stereotactic body radiotherapy in the treatment of head and neck cancer. Iqbal, MS., West, N., Richmond, N., et al.[2022]

Stereotactic body radiotherapy (SBRT) is a safe and feasible treatment option for patients with recurrent squamous cell carcinoma of the head and neck, showing minimal toxicities and no severe treatment-related side effects (grade 4 or 5).

In a study of 85 patients, SBRT resulted in a 1-year local control rate of 51.2% and a median overall survival of 11.5 months, with better outcomes observed in patients receiving doses of 35 Gy or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic body radiation therapy in the treatment of previously-irradiated recurrent head and neck carcinoma: updated report of the University of Pittsburgh experience. Rwigema, JC., Heron, DE., Ferris, RL., et al.[2019]

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 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]

Citations

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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.

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Standard versus fractionated high-dose cisplatin plus ... Nomogram for predicting survival in patients receiving definitive chemoradiation for locally advanced squamous cell carcinoma of the head and neck.