De-intensified Chemoradiotherapy for Oropharyngeal Cancer

(PROTEcT Trial)

Recruiting at 1 trial location

Overseen By Kelsey Meyer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: AHS Cancer Control Alberta

Disqualifiers: Metastatic disease, Prior head and neck cancer, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses lower doses of radiation and standard chemotherapy to treat patients with a specific type of throat cancer, aiming to reduce side effects while effectively treating the cancer.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators or your doctor for guidance.

What data supports the effectiveness of the treatment De-intensified chemoradiotherapy for oropharyngeal cancer?

Research shows that de-intensified chemoradiotherapy for HPV-positive oropharyngeal cancer can maintain similar control of the disease and survival rates while reducing the side effects compared to standard treatments. This approach is based on the favorable prognosis of HPV-associated cancers, allowing for less aggressive treatment without compromising outcomes. ^{1 2 3 4 5}

Is de-intensified chemoradiotherapy safe for humans?

De-intensified chemoradiotherapy for HPV-associated oropharyngeal cancer has been studied and shows promise in reducing side effects while maintaining effectiveness. However, some patients still experience significant side effects like severe mouth sores and difficulty swallowing, so long-term follow-up is needed to confirm its safety. ^{1 5 6 7 8}

How is de-intensified chemoradiotherapy different from other treatments for oropharyngeal cancer?

De-intensified chemoradiotherapy for oropharyngeal cancer is unique because it uses lower doses of radiation and chemotherapy to reduce side effects while still effectively controlling the disease, especially in patients with HPV-positive tumors, which respond better to treatment. ^{1 3 9 10 11}

Research Team

Harvey Quon, MD

Principal Investigator

Tom Baker Cancer Centre

Eligibility Criteria

Adults with p16+ squamous cell carcinoma of the oropharynx, eligible for curative treatment, can join this trial. They must have certain tumor and nodal stages (T1-T3, N1-N2), good organ function, and an ECOG performance status of 0-2. Smokers and non-smokers are welcome. Those with metastatic disease, prior head and neck cancer/radiation, or who are pregnant cannot participate.

Inclusion Criteria

Smokers and non-smokers are included

I am 18 years old or older.

Provide informed consent

Exclusion Criteria

My cancer has spread to nearby lymph nodes or into the submandibular gland.

I have had head or neck cancer in the past 5 years.

My cancer has spread to other parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy

De-intensified radiotherapy to a dose of 60 Gy to the primary tumour and involved lymph nodes and 54 Gy to subclinical regions at risk in 30 fractions

6 weeks

Chemotherapy

Concurrent cisplatin or cetuximab administered as per standard of care

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• De-intensified chemoradiotherapy

Trial Overview The PROTEcT study is testing a de-intensified chemoradiotherapy approach for patients with p16+ oropharyngeal cancer. It's a single-arm prospective cohort study across multiple centers aiming to see if reducing radiation volume and dose is effective.

Participant Groups

Group I: De-intensified chemoradiotherapy Experimental Treatment 1 Intervention

Radiotherapy to a dose of 60 Gy to the primary tumour and involved lymph nodes and 54 Gy to subclinical regions at risk in 30 fractions. Reduced volume of elective nodal radiation.

De-intensified chemoradiotherapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as De-intensified chemoradiotherapy for:

• p16+ oropharyngeal cancer
• HPV-associated oropharyngeal squamous cell carcinoma

Approved in European Union as De-intensified chemoradiotherapy for:

• p16+ oropharyngeal cancer
• HPV-associated oropharyngeal squamous cell carcinoma

Approved in Canada as De-intensified chemoradiotherapy for:

• p16+ oropharyngeal cancer
• HPV-associated oropharyngeal squamous cell carcinoma

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Tom Baker Cancer Centre

Collaborator

Trials

30

Recruited

8,900+

Cross Cancer Institute

Collaborator

Trials

62

Recruited

19,200+

Findings from Research

In a phase II clinical trial involving 114 patients with HPV-associated oropharyngeal cancer, a de-intensified treatment regimen of 60 Gy radiotherapy and low-dose cisplatin resulted in excellent 2-year outcomes: 95% local-regional control and 86% progression-free survival.

The study found that this treatment approach minimized the need for chemotherapy and surgery, with no severe late adverse events reported, indicating a safer and effective option for patients with minimal smoking history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. Chera, BS., Amdur, RJ., Green, R., et al.[2021]

In a phase 2 trial involving 45 patients with HPV-positive oropharyngeal cancer, de-escalated chemoradiation therapy resulted in a low rate of gastrostomy tube placement (5%) and allowed 95% of patients to return to a normal diet after treatment, indicating improved functional outcomes.

Patients who had a normal BMI before treatment were able to recover to baseline BMI levels approximately 18 months post-therapy, suggesting that the treatment approach may help maintain nutritional status and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional Outcomes After De-escalated Chemoradiation Therapy for Human Papillomavirus-Positive Oropharyngeal Cancer: Secondary Analysis of a Phase 2 Trial. Hegde, JV., Shaverdian, N., Felix, C., et al.[2019]

HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is recognized as a distinct type of cancer that may benefit from personalized treatment strategies, including less invasive and less toxic therapies.

Current research is focused on de-escalation treatment strategies that aim to reduce the toxicity of standard treatments while maintaining effective disease control, but more conclusive results from ongoing trials are needed to determine the best approaches and which patients will benefit most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present and Future of De-intensification Strategies in the Treatment of Oropharyngeal Carcinoma. De Virgilio, A., Costantino, A., Mercante, G., et al.[2021]

In a phase 2 study involving 43 patients with favorable-risk HPV-associated oropharyngeal squamous cell carcinoma, a reduced intensity treatment of 60 Gy IMRT combined with low-dose cisplatinum resulted in a high pathologic complete response (pCR) rate of 86%.

The study also demonstrated a lower incidence of severe toxicities compared to standard treatments, with significant rates of mucositis and dysphagia, but overall, the treatment was well-tolerated, indicating a promising balance between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. Chera, BS., Amdur, RJ., Tepper, J., et al.[2022]

In a systematic review of 55 studies involving 38,929 patients with HPV+ oropharyngeal carcinoma, de-intensified treatment approaches were found to significantly reduce overall survival (OS) and progression-free survival (PFS) compared to standard treatments.

The analysis indicated that reduced intensity treatments also led to decreased locoregional and distant disease control, suggesting that de-escalation strategies may pose a risk of providing sub-optimal care for patients with HPV+ OPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment de-escalation for HPV+ oropharyngeal cancer: A systematic review and meta-analysis. Petrelli, F., Luciani, A., Ghidini, A., et al.[2022]

Oropharyngeal cancers caused by HPV are more sensitive to chemotherapy and radiation, leading to better outcomes compared to HPV-negative cancers, which raises questions about the intensity of current treatment protocols.

Ongoing de-escalation trials suggest that less intensive treatment regimens could maintain efficacy while reducing toxicity for HPV-positive patients, but clinicians are advised to wait for clinical trial results before changing treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment de-intensification strategies for HPV-driven oropharyngeal cancer: A short review]. Lahmamssi, C., Guy, JB., Benchekroun, N., et al.[2020]

A systematic review of 13 studies showed that reducing the radiation dose for HPV-related oropharyngeal carcinoma (OPC) to less than 66 Gy resulted in better overall survival rates (95.66% at 2 years and 91.51% at 3 years) compared to the standard dose (88.36% at 2 years and 87.46% at 3 years).

Reducing the radiation dose significantly decreased treatment-related side effects, with oral mucositis being the most common complication (36.4%), thus improving the quality of life for patients while still maintaining effective cancer control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-dose radiation in human papillomavirus-associated oropharyngeal carcinoma can improve outcome: a systematic review and meta-analysis. Yang, MQ., Liu, YC., Sui, JD., et al.[2023]

A systematic review of 10 prospective studies on therapy de-escalation for HPV-associated oropharyngeal cancer (OPC) suggests that reduced-dose chemoradiotherapy, especially when combined with induction chemotherapy, can achieve high 2-year progression-free survival (PFS) rates of 89% and overall survival (OS) rates of 96%.

While de-escalation strategies show promising efficacy, they also present some acute toxicities, with grade 3+ dysphagia and mucositis occurring in 9-39% of patients, indicating a need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials. Patel, RR., Ludmir, EB., Augustyn, A., et al.[2021]

Oropharyngeal carcinoma linked to human papillomavirus (HPV) is on the rise, but it has better treatment outcomes compared to traditional head and neck cancers, prompting a focus on treatment de-escalation strategies.

Current strategies for reducing treatment intensity include adjusting radiation doses, using selective nodal irradiation, and evaluating patient responses to induction chemotherapy, all aimed at minimizing side effects while preserving quality of life for younger, healthier patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional Radiation Therapy for Oropharyngeal Cancer in the HPV Era. Tam, M., Hu, K.[2019]

In a study of 62 patients with HPV+ oropharyngeal squamous cell carcinoma, a response-based de-escalation of radiotherapy and chemoradiotherapy resulted in high 2-year progression-free survival rates of 95% for low-risk and 94% for high-risk patients, demonstrating efficacy while reducing treatment intensity.

The study showed significantly lower rates of severe side effects, such as grade 3+ mucositis and PEG-tube use, in patients receiving lower doses of treatment (RT50 and CRT45) compared to standard care (CRT75), indicating a safer approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. Seiwert, TY., Foster, CC., Blair, EA., et al.[2023]

HPV-related oropharyngeal cancers, which are becoming more common, show better treatment responses and overall survival compared to traditional tobacco-related cases, highlighting the importance of understanding their distinct biological behavior.

Current treatment strategies involve multi-disciplinary approaches, including chemoradiation and surgery, with ongoing research focused on reducing treatment toxicity and exploring novel immunotherapies for patients with recurrent or metastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced oropharyngeal squamous cell carcinoma: Pathogenesis, treatment, and novel therapeutic approaches. Swiecicki, PL., Malloy, KM., Worden, FP.[2020]

References

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

Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. [2021]

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

Functional Outcomes After De-escalated Chemoradiation Therapy for Human Papillomavirus-Positive Oropharyngeal Cancer: Secondary Analysis of a Phase 2 Trial. [2019]

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

Present and Future of De-intensification Strategies in the Treatment of Oropharyngeal Carcinoma. [2021]

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

Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. [2022]

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

Treatment de-escalation for HPV+ oropharyngeal cancer: A systematic review and meta-analysis. [2022]

6. France pubmed.ncbi.nlm.nih.gov

[Treatment de-intensification strategies for HPV-driven oropharyngeal cancer: A short review]. [2020]

7. China pubmed.ncbi.nlm.nih.gov

Reduced-dose radiation in human papillomavirus-associated oropharyngeal carcinoma can improve outcome: a systematic review and meta-analysis. [2023]

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

De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials. [2021]

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

Regional Radiation Therapy for Oropharyngeal Cancer in the HPV Era. [2019]

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

OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. [2023]

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

Advanced oropharyngeal squamous cell carcinoma: Pathogenesis, treatment, and novel therapeutic approaches. [2020]