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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best way to combine the immunotherapy drugs ipilimumab (Yervoy) and nivolumab (Opdivo) with radiation to treat advanced throat cancer positive for HPV, a virus linked to some throat cancers. It evaluates the effectiveness of these treatments together and their potential side effects. Individuals recently diagnosed with a specific type of throat cancer, with symptoms visible on a scan, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study examined the safety of using nivolumab and ipilimumab with radiation therapy for cancer treatment. Researchers found that most patients tolerated this combination well. Common side effects included fatigue, skin reactions, and changes in blood tests, but these were usually manageable. Serious side effects occurred less frequently.

Both nivolumab and ipilimumab are already used to treat other types of cancer, providing some information about their safety. The current trial is in an early stage, and while initial results are promising, more research is needed to fully understand the safety of this treatment combination for throat cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining immunotherapy with radiation for throat cancer because it introduces a new way to harness the body's own immune system to fight cancer. Most standard treatments, like surgery, chemotherapy, and radiation therapy, work by directly attacking cancer cells. However, the combination of nivolumab and ipilimumab, two immunotherapy drugs, with Intensity-Modulated Radiation Therapy (IMRT) aims to enhance the immune system's ability to target and destroy cancer cells. This approach not only targets the cancer more precisely but also has the potential to reduce side effects and improve patient outcomes by minimizing damage to healthy tissues.

What evidence suggests that this trial's treatments could be effective for HPV positive throat cancer?

In this trial, participants will receive a combination of nivolumab and ipilimumab with Intensity-Modulated Radiation Therapy (IMRT) to treat HPV-positive throat cancer. Research has shown that using nivolumab and ipilimumab with radiation therapy might be promising, as these drugs help the immune system attack cancer cells more effectively. Some studies have found that combining these drugs with radiation leads to better results in similar cancers, suggesting it can slow tumor growth and spread. Although challenges with side effects exist, this treatment has the potential to improve cancer control. Researchers are examining whether this combination works better than standard treatments alone. ^{1 2 3 5 6}

Who Is on the Research Team?

Renata Ferrarotto, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03799445

NCT03799445 | Ipilimumab, Nivolumab, and Radiation ... Giving ipilimumab, nivolumab, and radiation therapy may work better in treating patients with HPV positive oropharyngeal squamous cell carcinoma. Detailed ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10401226/

Nivolumab and ipilimumab in combination with ... Outcomes. The primary endpoint of the study was safety of the combination of nivolumab and ipilimumab with radiation therapy as definitive ...

3. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2022/01/12568-Ipilimumab-with-nivolumab.pdf

Nivolumab (Opdivo) with ipilimumab (Yervoy) for recurrent, ... Head and neck cancers are often curable if diagnosed at an early stage. Risk factors include smoking tobacco and drinking alcohol. Symptoms may present as ...

4. redjournal.org redjournal.org/article/S0360-3016(20)33708-1/pdf

Nivolumab and Ipilimumab Combined with ... Conclusion: Compared with TP induction chemotherapy, GP significantly improved the treatment response rate and DFS among patients with LA-. NPC. Author ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425001198

Prospective Phase II Trial of Definitive Chemoradiation and ... Concurrent and adjuvant nivolumab did not improve PFS in locoregionally advanced HPV+ OPSCC and was associated with significant toxicity.

6. advancesradonc.org advancesradonc.org/article/S2452-1094(25)00119-8/fulltext

Prospective Phase II Trial of Definitive Chemoradiation and ... We conducted a prospective, single-institution phase II trial to test the hypothesis that the addition of nivolumab to definitive chemoradiation would ...