De-intensified Chemoradiotherapy for Oropharyngeal Cancer
(PROTEcT Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: AHS Cancer Control Alberta
Disqualifiers: Metastatic disease, Prior head and neck cancer, others
No Placebo Group
Approved in 3 Jurisdictions
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.
12345Is 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.
15678How 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.
1391011Eligibility 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
+8 more
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.
+5 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: De-intensified chemoradiotherapyExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cross Cancer InstituteEdmonton, Canada
Tom Baker Cancer CentreCalgary, Canada
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Who Is Running the Clinical Trial?
AHS Cancer Control AlbertaLead Sponsor
Tom Baker Cancer CentreCollaborator
Cross Cancer InstituteCollaborator
References
Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. [2021]To report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma.
Functional Outcomes After De-escalated Chemoradiation Therapy for Human Papillomavirus-Positive Oropharyngeal Cancer: Secondary Analysis of a Phase 2 Trial. [2019]To analyze functional outcomes for patients treated on a phase 2 trial of de-escalated chemoradiation therapy for human papillomavirus-positive oropharyngeal cancer.
Present and Future of De-intensification Strategies in the Treatment of Oropharyngeal Carcinoma. [2021]The treatment of patients with squamous cell carcinoma of the oropharynx (OPSCC) remains controversial. HPV positivity is widely accepted as a favorable prognostic factor, and HPV+ OPSCC is considered a distinct pathological entity with dedicated NCCN guidelines and may deserve a more personalized therapeutic strategy. The possibility to reduce surgical invasiveness and acute and late toxicity of radiotherapy/chemotherapy has led to the new concept of de-escalation treatment strategies. In particular, several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. The aim of the present review is to systematically illustrate the current status of research in de-intensification surgical and non-surgical strategies in the treatment of the OPSCC.
Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. [2022]To perform a prospective, multi-institutional, phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus-associated oropharyngeal squamous cell carcinoma.
Treatment de-escalation for HPV+ oropharyngeal cancer: A systematic review and meta-analysis. [2022]Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compared with HPV-counterparts, thereby pushing the adoption of de-intensification treatment approaches as new strategies to preserve superior oncologic outcomes while minimizing toxicity. We evaluated the effect of treatment de-intensification in terms of overall survival (OS), progression-free survival (PFS), locoregional and distant control (LRC and DM) by selecting prospective or retrospective studies, providing outcome data with reduced intensification versus standard curative treatment in HPV+ OPC patients, with a systematic analysis till September 2020. The primary outcome of interest was OS. Secondary endpoints were PFS, LRC, and DM expressed as HR. A total of 55 studies (from 1393 screened references) were employed for quantitative synthesis for 38 929 patients. Among n = 48 studies with data available, de-intensified treatments reduced OS in HPV+ OPCs (HR = 1.33, 95% CI 1.17-1.52; p
[Treatment de-intensification strategies for HPV-driven oropharyngeal cancer: A short review]. [2020]The incidence of oropharyngeal cancer induced by human papillomavirus (HPV) infection is steadily increasing in developed countries. These tumors are more chemoradiosensitive and have a better prognosis than HPV-negative one. In addition, they occur in younger and better-off patients with longer life expectancy. Current radiotherapy and chemotherapy protocols are currently being questioned as they may expose HPV-positive patients to excessive treatment and unnecessary toxic effects. Less intensive treatment regimens could possibly achieve similar efficacy with lower toxicity and improved quality of life. The aim of this work was to summarize the knowledge on these tumors and their implications for radiation oncologists. In this update, we will discuss ongoing de-escalation trials and highlight the issues raised by these studies. We will also comment on the results of recently published de-intensification studies. Three main strategies are analyzed in the present article: the de-escalation of the drug associated with radiotherapy, the de-escalation of the radiotherapy dose (in concomitant chemoradiotherapy, after induction chemotherapy, in a postoperative setting) and de-escalation of radiation target volumes. Our findings ultimately indicate that clinicians should not change the management of oropharyngeal cancer patients outside of clinical trials.
Reduced-dose radiation in human papillomavirus-associated oropharyngeal carcinoma can improve outcome: a systematic review and meta-analysis. [2023]Despite its effectiveness, the standard course of chemoradiation for the treatment of human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) results in considerable treatment-related adverse effects. Studies proved that HPV-positive OPC is very sensitive to radiotherapy. Using de-escalation therapy as a new strategy is critical to maintaining positive outcomes while alleviating side effects. However, some studies hold that reduced dose causes insufficient effect on tumor killing. We conducted this systematic review and meta-analysis of survival and adverse reactions in patients with HPV-related OPC by retrospective analysis and evaluated the therapeutic effect of reducing the radiation dose.
De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials. [2021]Numerous trials have been launched over the prior decade examining the safety and efficacy of therapy de-escalation in human papillomavirus (HPV)-associated oropharyngeal cancer (OPC). Because no summative assessment of these prospective trials exists to date, we systematically reviewed the outcomes and toxicities associated with therapy de-intensification for this population. PRISMA-guided systematic PubMed searches (along with articles known to the authors and references thereof) were performed for prospective studies reporting clinical outcomes and/or toxicities of de-intensified RT and/or systemic therapy (with or without surgery), exclusively for HPV-associated OPC. Ten prospective studies were analyzed. Performing a meta-analysis was not entirely possible owing to the heterogeneity of treatment paradigms and the lack of >2 studies for most paradigms; however, because just one paradigm (induction chemotherapy followed by reduced-dose RT and/or systemic therapy) had 4 associated articles, an exploratory meta-analysis was conducted for that subset. Two trials of dose-reduced concurrent chemoradiotherapy (60 Gy/weekly cisplatin) demonstrated 3-year distant metastasis-free survival and overall survival (OS) ranging from 91 to 100% and 95%, respectively; acute grade 3+ mucositis and dysphagia occurred in 33-35% and 21-39%, respectively. In the four trials of induction chemotherapy (platinum/taxane-based) followed by dose-reduced RT, 2-year progression-free and OS ranged from 80 to 95% and 83 to 98%, respectively; acute grade 3+ dysphagia, dermatitis, and mucositis ranged from 9 to 15%, 7 to 20%, and 9 to 30% (excluding one outlier), respectively. For these four trials, the exploratory meta-analysis showed a pooled 2-year PFS and OS of 89% (95% confidence interval, 80-96%) and 96% (92-99%). The pooled rates of grade ≥3 dysphagia, dermatitis, and mucositis were 13% (7-19%), 9% (5-14%), and 28% (9-53%). However, there was significant heterogeneity in the 2-year PFS (I2 = 57%, p = 0.07) and grade ≥3 mucositis (I2 90%, p < 0.01). Next, both randomized trials which replaced concurrent tri-weekly cisplatin with weekly cetuximab illustrated superior outcomes with the former. Lastly, two remaining trials (one using functional imaging to guide reduced-dose RT, and another examining reduced-dose postoperative RT) also showed satisfactory outcomes and toxicities. Taken together, dose-reduced chemoradiotherapy (with or without induction chemotherapy for patient/biology selection purposes) seems to be a promising de-escalation strategy for HPV-associated OPC, although replacement of concurrent cisplatin by cetuximab is not recommended. Long-term follow-up is required for firmer conclusions.
Regional Radiation Therapy for Oropharyngeal Cancer in the HPV Era. [2019]Oropharyngeal carcinoma associated with the human papillomavirus is increasing in incidence and represents a unique head and neck disease with favorable treatment outcomes. This review evaluates the evolving role of radiotherapy in regional management with an overall goal of treatment de-escalation in the appropriate patient. Determining the optimal approach and selection factors for treatment de-escalation is under active investigation. Response to induction chemotherapy, refining adverse pathologic factors after a primary surgical approach, decreasing radiation dose with or without chemotherapy in the definitive or adjuvant settings as well as more selective nodal level irradiation all are current strategies for treatment de-escalation. This review details the likely changes in regional radiotherapy management for oropharyngeal carcinoma in the modern human papillomavirus era and discusses future approaches to patient selection with the goal of reducing toxicities while maintaining function preservation and quality of life in group of patients who are younger and healthier than traditional head and neck cancer patients.
OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. [2023]Patients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy.
Advanced oropharyngeal squamous cell carcinoma: Pathogenesis, treatment, and novel therapeutic approaches. [2020]Oropharyngeal cancer accounts for approximately 2.8% of newly cancer cases. Although classically a tobacco related disease, most cases today are related to infection with human papilloma virus (HPV) and present with locally advanced tumors. HPV related tumors have been recognized as a molecularly distinct entity with higher response rates to therapy, lower rates of relapse, and improved overall survival. Treatment of oropharyngeal cancer entails a multi-disciplinary approach with concomitant chemoradiation. The role of induction chemotherapy in locally advanced tumors continues to be controversial however large studies have demonstrated no difference in survival or time to treatment failure. Surgical approaches may be employed with low volume oropharyngeal cancers and with development new endoscopic tools, more tumors are able to be resected via an endoscopic approach. Given advances in the understanding of HPV related oropharyngeal cancer, ongoing research is looking at ways to minimize toxicities via de-intensification of therapy. Unfortunately, some patients develop recurrent or metastatic disease. Novel therapeutics are currently being investigated for this patient population including immunotherapeutics. This review discusses the current understanding of the pathogenesis of oropharyngeal cancer and treatment. We also discuss emerging areas of research as it pertains to de-intensification as well novel therapeutics for the management of metastatic disease.