SABR Boost + Short-course Radiation for Oropharyngeal Cancer

(SHORT-OPC Trial)

Recruiting at 1 trial location

Overseen By Diane Trudel

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Non-Cisplatin chemotherapy

Disqualifiers: Previous head/neck irradiation, Pregnancy, Connective tissue disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 7 weeks

360 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating oropharyngeal cancer linked to the human papillomavirus (HPV). Researchers aim to determine if a shorter, more targeted radiation treatment, called SABR boost (Stereotactic Ablative Radiotherapy), combined with fewer chemotherapy rounds, matches the effectiveness of the usual longer treatment. Participants will receive either this new treatment or the standard 7-week chemoradiation course. Individuals diagnosed with HPV-related oropharynx cancer who plan to start curative chemoradiation might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants cannot have had prior induction chemotherapy or non-Cisplatin concurrent chemotherapy.

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

Research has shown that stereotactic ablative radiotherapy (SABR) is generally safe and well-tolerated. Studies indicate that SABR can effectively treat small, localized cancers, such as glottic cancer in the throat, with patients often experiencing positive outcomes. One study found that SABR was safe in various cancer treatments, and most patients responded well.

In a study on head and neck cancer, using SABR as an additional treatment showed promising results. Most patients responded well, with many seeing their cancer completely disappear. Although specific data on the safety of combining SABR with reduced chemoradiation for oropharyngeal cancer is lacking, these findings suggest that the treatment is manageable for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SABR boost combined with de-escalated chemoradiation for oropharyngeal cancer because it offers a new approach to treatment. Unlike the standard treatment, which involves high-dose radiation over a longer period, the SABR boost delivers a precise, high-dose radiation in just 2 fractions, followed by a reduced overall radiation dose. This method aims to minimize side effects while maintaining effectiveness, offering a potentially gentler treatment option for patients. Additionally, the use of concurrent high-dose Cisplatin is streamlined to two cycles, which could further reduce the burden on patients compared to the standard 2-3 cycles.

What evidence suggests that this trial's treatments could be effective for oropharyngeal cancer?

Research has shown that using SABR boost with reduced chemoradiation, one of the treatment options in this trial, is promising. One study reported a 100% major response rate for head and neck cancer, with 80.8% of patients achieving a complete response. Stereotactic body radiotherapy (SBRT) as an additional treatment proves effective, particularly for small tumors near sensitive areas. This approach is considered innovative and effective, offering hope for treating oropharyngeal cancer linked to human papillomavirus (HPV). Meanwhile, the standard chemoradiation arm in this trial serves as a comparator to evaluate the effectiveness of the SABR boost approach. ^{2 3 5 6 7}

Who Is on the Research Team?

Khalil Sultanem, MD

Principal Investigator

Montreal Jewish General Hospital

Jack Phan, MD,PHD

Principal Investigator

M.D. Anderson Cancer Center

Houda Bahig, MD PhD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Phuc-Felix Nguyen-Tan, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

David Palma, MD PhD

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HPV-positive oropharyngeal cancer, who haven't had major head and neck surgery or radiation before. They should be in good enough health to follow the trial procedures and not pregnant. The cancer must be at an early stage (Stage I-II) and the primary tumor smaller than 30 cc.

Inclusion Criteria

Ability to provide written informed consent.

I am of child-bearing age and my pregnancy test is negative.

My breast cancer is in an early to mid-stage, but has spread to nearby lymph nodes.

Exclusion Criteria

I have had radiation therapy on my head or neck.

I have received initial chemotherapy.

You are pregnant or currently breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either SABR boost and de-escalated chemoradiation or standard chemoradiation

7 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular visits at 1, 3, 6, 12 months, and yearly from years 2-5

What Are the Treatments Tested in This Trial?

Interventions

• SABR boost and de-escalated chemoradiation
• Standard chemoradiation

Trial Overview

The study compares a shorter course of chemoradiation with a stereotactic boost directly to the tumor against the standard longer seven-week chemoradiation treatment for HPV-associated oropharynx cancer.

How Is the Trial Designed?

Group I: SABR boost and de-escalated chemoradiation Experimental Treatment 1 Intervention

SABR boost of 14 Gy in 2 fractions to the GTV, immediately followed by de-escalated chemoradiation. De-escalated chemoradiation will consist in 40 Gy in 20 fractions with concurrent high dose Cisplatin (3-weekly, 100 mg/m2) for 2 cycles, aiming for a cumulative dose of 200 mg/m2.

Group II: Standard chemoradiation Active Control 1 Intervention

The standard arm will consist of conventionally radiation to a dose of 70 Gy in 33 fractions concurrently with high dose Cisplatin (3-weekly, 100 mg/m2) for 2-3 cycles, aiming for a cumulative dose of ≥ 200 mg/m2.

SABR boost and de-escalated chemoradiation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as SABR for:

• Non-small cell lung cancer (NSCLC)
• Oligometastatic disease
• Recurrent head and neck cancer

Approved in Canada as SABR for:

• Oligometastatic disease
• Recurrent head and neck cancer

Approved in European Union as SABR for:

• Non-small cell lung cancer (NSCLC)
• Oligometastatic disease
• Recurrent head and neck cancer

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Collaborator

Trials

686

Recruited

427,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Collaborator

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Collaborator

Trials

678

Recruited

421,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Lawson Health Research Institute

Collaborator

Trials

684

Recruited

432,000+

Jewish General Hospital

Collaborator

Trials

144

Recruited

283,000+

Published Research Related to This Trial

Frameless stereotactic body radiotherapy (SBRT) was found to be a safe and effective treatment option for boosting primary oropharyngeal cancers in 51 patients who were not suitable for standard brachytherapy, achieving 2-year local control, disease-free survival, and overall survival rates of 86%, 80%, and 82%, respectively.

The treatment was well tolerated with no severe (Grade 4 or 5) toxicities reported, and only 28% of patients experienced Grade 2 or higher late toxicity, indicating that SBRT can be a viable alternative with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy: a promising treatment option for the boost of oropharyngeal cancers not suitable for brachytherapy: a single-institutional experience. Al-Mamgani, A., Tans, L., Teguh, DN., et al.[2012]

In a study of 244 patients with oropharyngeal squamous cell carcinoma treated with radiation doses greater than 72 Gy, both simultaneous integrated boost (SIB) and brachytherapy boost showed similar overall survival (OS) rates and progression-free survival (PFS) outcomes, indicating that either method can be effective for dose escalation.

There were no significant differences in the incidence of severe side effects (grade ≥3) between the two treatment modalities, suggesting that both approaches are similarly safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation in oropharyngeal cancer: a comparison of simultaneous integrated boost and brachytherapy boost. Embring, A., Onjukka, E., Mercke, C., et al.[2023]

Stereotactic body radiotherapy (SBRT) as a boost treatment for head and neck cancer showed a 100% major response rate, with 80.8% of patients achieving complete responses after a median follow-up of 56 months.

Despite its effectiveness in controlling local tumors, 34.6% of patients experienced severe late toxicities, indicating a need for improved dose fractionation and patient selection to minimize complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome and toxicity of hypofractionated stereotactic body radiotherapy as a boost treatment for head and neck cancer: the importance of boost volume assessment. Lee, DS., Kim, YS., Cheon, JS., et al.[2021]

In a study of 195 patients with oropharyngeal squamous cell carcinoma treated with a stereotactic body radiotherapy (SBRT) boost, the 5-year disease-specific survival rate was 85%, indicating good efficacy of this treatment approach.

However, the treatment was associated with a significant rate of Grade ≥3 toxicities, including 28% experiencing severe side effects like soft tissue necrosis and osteoradionecrosis, highlighting the need for strategies to reduce these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes following stereotactic body radiotherapy boost for oropharyngeal squamous cell carcinoma. Baker, S., Verduijn, GM., Petit, S., et al.[2019]

In a study of 25 head and neck cancer patients treated with hypofractionated stereotactic radiotherapy (hSRT) using CyberKnife, there was a high response rate of 96%, with 18 patients achieving complete responses and 6 partial responses after a median follow-up of 28 months.

The study found that smaller planning target volumes (PTV ≤ 20 cm³) were associated with significantly better progression-free survival (92%) and overall survival (100%) compared to larger volumes, indicating that both the size of the treatment area and initial response to treatment are important predictors of patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated stereotactic radiotherapy using CyberKnife as a boost treatment for head and neck cancer, a multi-institutional survey: impact of planning target volume. Yamazaki, H., Ogita, M., Himei, K., et al.[2018]

In a study of 195 patients with oropharynx cancer, the 5-year local control rate was 90% and regional control was 93% after receiving intensity-modulated radiotherapy and a stereotactic body radiotherapy boost.

Despite the high overall control rates, 76% of local recurrences occurred within the radiation field, which is significantly higher than the 0%-5% seen with conventional treatments, indicating that while the treatment is effective, it may lead to increased local failures outside the targeted area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locoregional failures and their relation to radiation fields following stereotactic body radiotherapy boost for oropharyngeal squamous cell carcinoma. Baker, S., Verduijn, G., Petit, S., et al.[2020]

A consensus document was created by trial management groups from six UK studies on stereotactic ablative radiotherapy (SABR) to establish updated organ at risk dose constraints, enhancing safety during treatment.

This unified approach aims to standardize the implementation of SABR across the UK, enabling better comparisons of toxicity and efficacy between different SABR studies both nationally and internationally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Hanna, GG., Murray, L., Patel, R., et al.[2022]

Stereotactic ablative radiotherapy (SABR) for recurrent head and neck cancer in previously irradiated areas showed a 1-year local control rate of 64.2% and an overall survival rate of 67.5% over a median follow-up of 12 months, indicating its efficacy in this challenging patient population.

SABR was well tolerated, with only 31.3% of patients experiencing acute Grade 2 skin toxicity and 28% experiencing Grade 3 mucosal toxicity, which is significantly lower than the 50-70% toxicity rates associated with other salvage treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy (SABR) for recurrent and previously irradiated head and neck cancers. Anand, AK., Dua, B., Bansal, AK., et al.[2022]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10999469/

Stereotactic ablative radiotherapy for treating primary head ...

The indication for stereotactic ablative radiotherapy in head and neck remains rare. Emerging data demonstrate a possible utility of SABR as a boost.

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withpower.com

withpower.com/trial/phase-3-papilloma-1-2020-26449

SABR Boost + Short-course Radiation for Oropharyngeal ...

Stereotactic body radiotherapy (SBRT) as a boost treatment for head and neck cancer showed a 100% major response rate, with 80.8% of patients achieving complete ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0360301624029729

Stereotactic Ablative Radiotherapy for T1 to T2 Glottic ...

Highly conformal stereotactic radiation therapy appears safe and efficacious for early-stage glottic larynx cancer, with encouraging patient-reported outcomes.

4.

redjournal.org

redjournal.org/article/S0360-3016(24)02972-9/abstract

Mature Results From the Phase 2 GLoTtic Larynx-SABR Trial

Highly conformal stereotactic radiation therapy appears safe and efficacious for early-stage glottic larynx cancer, with encouraging patient-reported outcomes.

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38590327/

Stereotactic ablative radiotherapy for treating primary head ...

Conclusions: SABR is an innovative, effective and promising treatment modality for small targets, especially in near proximity to organs at risk ...

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clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT06078813

Spine SABR - Dose-escalated Stereotactic Ablative Body ...

This study will look at treatment for patients that have already been diagnosed with cancer, but develop a new tumor(s) in the spine.

7.

jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2773455

Safety and Survival Rates Associated With Ablative ...

The findings of this study suggest that stereotactic ablative radiotherapy is generally safe and well tolerated in the oligometastatic setting.