Immunotherapy + Radiation for Throat Cancer

Overseen By Maura Gillison

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Metastatic disease, Prior chemotherapy, Autoimmune disease, Pregnancy, 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: 11

37 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects and best dose of ipilimumab, nivolumab, and radiation therapy and how well they work in treating patients with advanced human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving ipilimumab, nivolumab, and radiation therapy may work better in treating patients with HPV positive oropharyngeal squamous cell carcinoma.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic immunosuppressive therapy or have an active autoimmune disease requiring treatment, you may need to consult with the trial sponsor.

What data supports the effectiveness of the treatment Intensity-Modulated Radiation Therapy (IMRT) for throat cancer?

Research shows that Intensity-Modulated Radiation Therapy (IMRT) can deliver high doses of radiation to cancerous areas while reducing exposure to nearby healthy tissues, which may lead to fewer side effects and improved safety for patients with head and neck cancers. ^{1 2 3 4 5}

Is the combination of immunotherapy and radiation therapy generally safe for humans?

Intensity-modulated radiation therapy (IMRT) has been shown to reduce radiation doses to normal tissues, which can lower the risk of side effects, but it can still cause issues like skin and oral mucosal toxicity. While IMRT is generally considered safe, there are concerns about potential long-term risks, such as radiation-related cancer, especially in younger patients. ^{3 4 6 7 8}

How is the treatment of Immunotherapy + Radiation for Throat Cancer different from other treatments?

This treatment combines immunotherapy drugs, Ipilimumab and Nivolumab, with Intensity-Modulated Radiation Therapy (IMRT), which is a precise form of radiation that targets cancer cells while sparing healthy tissue. The use of these immunotherapy drugs, which help the immune system attack cancer cells, alongside IMRT, is a novel approach that may enhance the effectiveness of treatment for throat cancer compared to traditional methods. ^{1 2 9 10 11}

Research Team

Maura Gillison, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced HPV-positive oropharyngeal squamous cell carcinoma. Participants must have certain blood counts, organ function tests within normal ranges, and a confirmed diagnosis through specific tests. Pregnant women, those with other cancers (except some skin cancers), previous radiation in the same area, severe allergies to contrast material, active infections or autoimmune diseases are excluded.

Inclusion Criteria

I have had a neck FDG-PET/CT scan within the last 28 days.

I've had a detailed chest scan within the last 28 days.

My kidney function is normal, with creatinine levels below 1.5 mg/dl or clearance above 50 ml/min.

Exclusion Criteria

My cancer is in the neck but its original source is unknown.

I have not had chemotherapy for my current cancer but may have for another.

My scans show cancer has spread below my collarbone.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Immunotherapy

Participants receive nivolumab and ipilimumab intravenously over 6 weeks for 2 cycles

12 weeks

3 visits (in-person) per cycle

Radiation Therapy

Participants undergo intensity-modulated radiation therapy (IMRT) 5 days a week for 6 weeks

6 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months for 2 years, then every 6 months for 3 years, and annually thereafter

Treatment Details

Interventions

• Intensity-Modulated Radiation Therapy
• Ipilimumab
• Nivolumab

Trial Overview The study is testing the combination of two immunotherapy drugs—Ipilimumab and Nivolumab—with intensity-modulated radiation therapy to see if they improve outcomes for patients. The trial will also determine the best doses of these drugs when used together with radiation.

Participant Groups

Group I: Treatment (nivolumab, ipilimumab, IMRT) Experimental Treatment 5 Interventions

Patients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every for 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of cycle 2, patients also undergo IMRT 5 days a week (Monday-Friday) 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 10 patients with head and neck squamous cell carcinoma treated with intensity-modulated radiotherapy (IMRT), no patients experienced death or loco-regional relapse, indicating promising efficacy of the treatment.

The study found that limiting the radiation dose to the contralateral parotid gland was more achievable with a maximum IMRT dose of 50 Gy, resulting in lower acute toxicity and a 50% rate of grade 0-1 late xerostomia at 3 months, suggesting potential for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intensity-modulated radiation therapy for head and neck cancers with bilateral irradiation of the neck : preliminary results]. Lapeyre, M., Marchesi, V., Mege, A., et al.[2018]

The SMART technique for intensity modulated radiotherapy (IMRT) significantly reduces maximum and mean radiation doses to the skin and oral cavity in head and neck cancer patients, while maintaining acceptable coverage of the planning target volume (PTV).

In a study of 16 patients, the SMART technique reduced skin maximum doses from 64.2 Gy to 55.9 Gy and mean doses from 26.7 Gy to 20.2 Gy, indicating a potential for less treatment-related morbidity, particularly in skin toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin/mucosa avoidance radiotherapy (SMART) versus conventional volumetric arc-based radiotherapy (VMAT) for the treatment of head and neck cancer: Dosimetric feasibility study. Anderson, C., MacDonald, RL., Wilke, D.[2023]

Intensity-modulated radiation therapy (IMRT) allows for higher doses of radiation to be delivered precisely to cancerous areas while minimizing exposure to surrounding healthy tissues, which can improve safety and reduce side effects.

IMRT is particularly beneficial for treating head and neck cancers due to the close proximity of tumors to critical structures, although there are concerns about the potential long-term risks of radiation exposure to non-target tissues, especially in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy in the treatment of head and neck cancer. Eisbruch, A.[2018]

Intensity-modulated radiotherapy (IMRT) shows excellent local-regional control rates of 92% for patients with squamous cell carcinoma of the oropharynx, based on a study of 107 patients with a median follow-up of 29 months.

Despite the high local control, distant metastases were a significant concern, with 7 patients experiencing them as the first site of failure, highlighting the need for ongoing monitoring and potential additional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: clinical outcomes and patterns of failure. Daly, ME., Le, QT., Maxim, PG., et al.[2022]

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]

Intensity modulated radiation treatment (IMRT) for oropharyngeal squamous cell carcinoma showed excellent locoregional control, with a 3-year locoregional progression-free survival rate of 98.8% among 66 patients treated between 2000 and 2004.

Despite the high locoregional control, there was a concerning rate of distant metastasis, with a 3-year distant metastasis-free survival rate of only 80.4%, indicating a need for further research into systemic treatments for patients at risk of distant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. Yao, M., Nguyen, T., Buatti, JM., et al.[2006]

References

1. France pubmed.ncbi.nlm.nih.gov

[Intensity-modulated radiation therapy for head and neck cancers with bilateral irradiation of the neck : preliminary results]. [2018]

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

Intensity-modulated radiotherapy for locally advanced cancers of the larynx and hypopharynx. [2022]

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

Skin/mucosa avoidance radiotherapy (SMART) versus conventional volumetric arc-based radiotherapy (VMAT) for the treatment of head and neck cancer: Dosimetric feasibility study. [2023]

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

Intensity-modulated radiation therapy in the treatment of head and neck cancer. [2018]

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

Impact of intensity-modulated radiotherapy on health-related quality of life for head and neck cancer patients: matched-pair comparison with conventional radiotherapy. [2022]

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

Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: clinical outcomes and patterns of failure. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Intensity modulated radiotherapy for anal canal squamous cell carcinoma: A 16-year single institution experience. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Intensity-modulated Radiotherapy for Anal Cancer: Dose-Volume Relationship of Acute Gastrointestinal Toxicity and Disease Outcomes. [2019]

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

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

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

Treatment outcomes and HPV characteristics for an institutional cohort of patients with anal cancer receiving concurrent chemotherapy and intensity-modulated radiation therapy. [2019]

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

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. [2006]