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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study seeks to gain new knowledge about the addition of a carefully targeted "boost" dose of radiation as a possible treatment for recurrent or metastatic head or neck cancer. The name of the study intervention involved in this study is stereotactic body radiotherapy, which is a way of delivering radiation in a more precisely targeted way and with a higher dose than conventional radiotherapy.

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 data supports the effectiveness of the treatment Stereotactic Radiotherapy + Cisplatin for Head and Neck Cancer?

Research shows that combining Intensity Modulated Radiation Therapy (IMRT) with platinum-based chemotherapy like cisplatin is a standard approach for head and neck cancer, offering good tumor control with reduced side effects compared to traditional methods. Additionally, Stereotactic Body Radiotherapy (SBRT) has been explored for recurrent cases, indicating potential benefits in managing difficult-to-treat head and neck cancers. ^{1 2 3 4 5}

Is the combination of stereotactic radiotherapy and cisplatin generally safe for humans?

Research shows that using cisplatin with intensity-modulated radiation therapy (IMRT) for head and neck cancer has acceptable safety levels, though more severe side effects can occur when chemotherapy is added. No patients experienced the most severe level of toxicity, and all completed their treatment without needing to stop due to side effects. ^{4 6 7 8 9}

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

This treatment combines Stereotactic Body Radiotherapy (SBRT), which delivers high doses of radiation precisely to the tumor, with Cisplatin, a chemotherapy drug, to enhance effectiveness. Unlike traditional methods, SBRT allows for more targeted radiation, potentially reducing damage to surrounding healthy tissue and improving outcomes for patients with head and neck cancer. ^{1 5 8 10 11}

Research Team

Jonathan D. Schoenfeld, MD MPH

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Survey of current practices from the International Stereotactic Body Radiotherapy Consortium (ISBRTC) for head and neck cancers. [2018]

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

Phase 1 Dose Escalation of Stereotactic Body Radiation Therapy and Concurrent Cisplatin for Reirradiation of Unresectable, Recurrent Squamous Cell Carcinoma of the Head and Neck. [2023]

3. United States 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. [2022]

4. 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]

5. Germany pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2019]

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

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

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

A Multi-institutional Comparison of SBRT and IMRT for Definitive Reirradiation of Recurrent or Second Primary Head and Neck Cancer. [2020]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

A systematic review and practical considerations of stereotactic body radiotherapy in the treatment of head and neck cancer. [2022]

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

Stereotactic Radiation Therapy for De Novo Head and Neck Cancers: A Systematic Review and Meta-Analysis. [2022]