Radiotherapy for Throat Cancer

(SAVER Trial)

Not currently recruiting at 5 trial locations

Overseen By Matthew Witek, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Disqualifiers: Oral cancer, Metastasis, Prior chemotherapy, others

Stay on Your Current Meds You can continue your current medications while participating

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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of using radiotherapy for individuals with p16 positive oropharyngeal squamous cell carcinoma, a specific type of throat cancer. The goal is to determine if targeting smaller areas with radiation can effectively prevent the cancer from recurring on the opposite side of the throat. Participants will receive one of two advanced radiation therapies: intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) or pencil beam proton therapy (PBPT). This trial may suit those with the specified type of throat cancer who require additional radiotherapy. 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 therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that both Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) are generally well-tolerated treatments for head and neck cancers. Studies have found that VMAT effectively controls cancer in these areas. IMRT tends to cause fewer short-term side effects compared to some other treatments and has few long-term side effects.

Pencil Beam Proton Therapy (PBPT) is another type of radiotherapy used in this trial. Research indicates that PBPT may result in fewer issues for healthy tissues than traditional radiotherapy. Patients have reported a good quality of life after receiving this therapy, and it is generally well tolerated.

Since this is a Phase 2 trial, earlier studies have already shown some safety for the treatment. This provides some confidence in its safety for the current study, but the main goal now is to assess its effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for throat cancer because they offer more precise targeting of tumors while sparing healthy tissue. Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are advanced forms of radiation that allow doctors to shape the radiation beams, minimizing exposure to surrounding healthy areas. Pencil beam proton therapy (PBPT) takes precision a step further by using proton particles, which can be controlled to stop exactly at the tumor, reducing collateral damage. These methods aim to reduce side effects and improve outcomes compared to traditional radiation therapies.

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

Research has shown that both Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) effectively treat head and neck cancers, including throat cancer. Studies have found that IMRT surpasses older methods like 3D-CRT, resulting in higher survival rates. Specifically, for patients with oropharyngeal cancer, IMRT has a 5-year survival rate of about 61.3%. In this trial, participants will receive either IMRT/VMAT or Pencil Beam Proton Therapy (PBPT), which may cause fewer side effects than IMRT, with less short-term and long-term harm. Patients treated with proton therapy have reported a better quality of life compared to those treated with photon-based therapies like IMRT. Both treatments offer promising options for those considering joining clinical trials for throat cancer treatments. ^{2 6 7 8 9}

Who Is on the Research Team?

Matthew E. Witek

Principal Investigator

University of Maryland/Maryland Proton Treatment Center

Are You a Good Fit for This Trial?

This trial is for adults with p16 positive oropharyngeal squamous cell carcinoma needing radiotherapy. They must have a good performance status, no prior invasive malignancies within 3 years (except skin cancer), and agree to use contraception if applicable. Pregnant/nursing individuals, those with certain head/neck surgeries, previous chemotherapy/radiotherapy for the study cancer, or evidence of contralateral nodal disease are excluded.

Inclusion Criteria

Does the patient require elective contralateral radiotherapy in the definitive or adjuvant setting (i.e. base of tongue primary or tonsil with base of tongue invasion, soft palate invasion, or medialized as defined by > 1/3 of the distance from the tonsil to the midline of the soft palate?

Was the patient's Zubrod Performance Status 0-1 within 30 days prior to registration?

Does the patient have clinical stage T1-4, N0, N1 or N3, and M0 disease (AJCC 8th edition) as defined by physical examination and appropriate imaging (PET/CT preferred, CT neck with IV contrast with CT chest without contrast as recommended alternative to PET/CT)?

Exclusion Criteria

Does the patient have a carcinoma of the neck of unknown primary origin?

Does the patient have prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years?

Did the patient have prior surgery of the head and neck excluding superficial removal of cutaneous skin malignancies?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy Treatment

Participants receive reduced contralateral elective nodal volume treatment via IMRT/VMAT or PBPT

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on nodal failure, PEG-tube rate, xerostomia, and dysphagia

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT)
• Pencil beam proton therapy (PBPT)

Trial Overview The trial tests whether reducing radiation treatment volumes on one side of the neck can prevent cancer recurrence in patients undergoing definitive or adjuvant radiotherapy. It compares Intensity Modulated Radiotherapy (IMRT)/Volumetric Modulated Arc Therapy (VMAT) against Pencil Beam Proton Therapy (PBPT).

How Is the Trial Designed?

Group I: Reduced C/L elective nodal volume Experimental Treatment 1 Intervention

All patients will receive the reduced C/L elective nodal volume as described. Treatment will be delivered via IMRT/VMAT or PBPT.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

Volumetric Modulated Arc Therapy (VMAT) significantly reduces radiation exposure to critical organs, such as the parotid glands and oral cavity, compared to Intensity-Modulated Radiation Therapy (IMRT), with average doses decreasing from 27.2 Gy to 25.0 Gy and from 39.4 Gy to 36.7 Gy, respectively.

VMAT also offers a substantial reduction in treatment delivery time, averaging 5:54 minutes compared to 13:15 minutes for IMRT, enhancing patient comfort and potentially minimizing movement during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional comparison of volumetric modulated arc therapy vs. intensity-modulated radiation therapy for head-and-neck cancer: a planning study. Holt, A., Van Gestel, D., Arends, MP., et al.[2022]

Intensity-modulated proton therapy (IMPT) for oropharyngeal carcinoma shows a potential reduction in severe weight loss and feeding tube dependency compared to intensity-modulated radiotherapy (IMRT), based on a study of 150 matched patients with a median follow-up of 32 months.

Despite these benefits, there were no significant differences in overall survival or progression-free survival between IMPT and IMRT, indicating that IMPT does not compromise treatment effectiveness while potentially improving quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated proton beam therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for patients with oropharynx cancer - A case matched analysis. Blanchard, P., Garden, AS., Gunn, GB., et al.[2022]

Intensity modulated proton beam therapy (IMPT) significantly reduces the average radiation dose to tooth-bearing regions in head and neck cancer patients compared to photon-based volumetric modulated arc therapy (VMAT), indicating a safer option for preserving dental health during treatment.

In a study of 121 patients, factors such as oral cavity tumors and advanced T3-T4 tumors were identified as risk factors for receiving a cumulative radiation dose of ≥40 Gy to tooth-bearing areas, which is critical for determining the need for prophylactic dental extractions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Planned dose of intensity modulated proton beam therapy versus volumetric modulated arch therapy to tooth-bearing regions. Alberga, JM., Meijer, J., Raghoebar, GM., et al.[2023]

In a study of 385 head and neck cancer patients treated with advanced radiotherapy techniques (IMRT/VMAT) over a median follow-up of 6.4 years, locoregional control rates were high, with 2- and 5-year rates of 78.2% and 74.2%, respectively, indicating effective treatment delivery.

The study found very few recurrences outside the high-dose treatment areas, suggesting that target volume definition and treatment delivery were accurate, which is crucial for improving patient outcomes in future research on dose escalation or proton therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrence Patterns After IMRT/VMAT in Head and Neck Cancer. Bollen, H., van der Veen, J., Laenen, A., et al.[2022]

In a study of 205 patients with advanced-stage oropharynx cancer, proton beam therapy (PBT) was found to significantly reduce the probability of treatment-related complications, such as severe dysphagia and xerostomia, compared to intensity-modulated radiation therapy (IMRT).

The normal tissue complication probability (NTCP) models indicated that PBT resulted in lower predicted toxicity rates at 6 months post-treatment, highlighting its potential as a safer option for patients undergoing radiation therapy for oropharyngeal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Model-Based Approach to Predict Short-Term Toxicity Benefits With Proton Therapy for Oropharyngeal Cancer. Rwigema, JM., Langendijk, JA., Paul van der Laan, H., et al.[2019]

Intensity modulated proton therapy (IMPT) shows significant dosimetric advantages over traditional intensity modulated radiation therapy (IMRT) for head and neck cancers, particularly in sparing nearby organs like the larynx and salivary glands.

Clinical evidence suggests that IMPT can reduce treatment-related toxicities, such as the need for feeding tubes, indicating its potential benefits in improving patient quality of life during and after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated proton therapy (IMPT) - The future of IMRT for head and neck cancer. Moreno, AC., Frank, SJ., Garden, AS., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4282814/

Volumetric-Modulated Arc Therapy for Oropharyngeal ... Intensity-modulated radiation therapy (IMRT) has been demonstrated to be superior to three-dimensional conformal radiotherapy (3D-CRT) for head and neck cancer ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1120179714005262

Volumetric-modulated arc therapy for oropharyngeal ... Intensity-modulated radiation therapy (IMRT) has been demonstrated to be superior to three-dimensional conformal radiotherapy (3D-CRT) for head and neck cancer ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6006

Phase III randomized trial of intensity-modulated proton ... This study was designed to compare the outcomes for patients with OPC after chemoradiation therapy (CRT) with IMRT vs IMPT. Methods: This is a ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2798320

Toxicity Profiles and Survival Outcomes Among Patients ... In this cohort study of 292 patients with nonmetastatic OPC, IMPT was associated with fewer acute toxic effects compared with IMRT and with few chronic toxic ...

5. link.springer.com link.springer.com/article/10.1007/s42399-023-01562-5

Clinical Efficacy and Complications of Intensity-modulated ... Based on data from November 2022, the 5-year overall survival (OS) for OPC is reported to be 61.3% [5]. Intensity-modulated radiation therapy ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11194100/

Comparison of Volumetric Modulated Arc Therapy (VMAT) ... This study examines the outcomes of locally advanced head and neck squamous cell carcinoma (HNSCC) following the adoption of conventional ...

7. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1272856/full

Outcomes among oropharyngeal and oral cavity cancer ... Our outcomes for postoperative VMAT for oral cavity and oropharyngeal cancers are encouraging, with high rates of loco-regional control.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9652753/

Toxicity Profiles and Survival Outcomes Among Patients ... This cohort study compares the toxic effects and oncologic outcomes associated with intensity-modulated radiation therapy (IMRT) vs intensity-modulated proton ...

9. ar.iiarjournals.org ar.iiarjournals.org/content/36/7/3451

Outcome and Toxicity of Volumetric Modulated Arc Therapy ... This technique has been studied for dosimetric benefit in head and neck cancer (12-14), but few studies have explored its possible clinical benefits (15-17). In ...