Proton Beam Therapy for Chordoma

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Previous irradiation, Metastatic disease, Concurrent malignancy, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 35

Duration: 7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether proton beam therapy, alone or with photon beam radiation, effectively treats skull base chordoma, a rare bone tumor. Researchers aim to evaluate the effectiveness and safety of these treatments. Individuals with a confirmed diagnosis of this tumor who have undergone surgery to remove as much of it as possible may qualify. The study seeks to determine if combining these radiation therapies yields better results. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 has shown that proton beam therapy is generally safe for treating chordomas, a type of tumor. Studies indicate it achieves excellent safety results with a very low risk of treatment failure. Serious brain damage, known as CNS necrosis, occurs in less than 1% of patients.

Additionally, high-dose proton therapy, whether used alone or with other treatments like photon therapy, has proven both safe and effective. Combining photon beam therapy with proton therapy can distribute the radiation dose more evenly without major safety concerns. Overall, both proton and photon therapies are well-tolerated by patients with chordomas. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about proton beam therapy for chordoma because it offers a more precise way to target tumors compared to traditional radiation therapies. Unlike conventional photon radiation, proton beam therapy can deliver higher doses of radiation directly to the tumor with minimal damage to surrounding healthy tissues. This precision is particularly important in treating chordomas, which are often located near critical structures like the spinal cord and brainstem. Additionally, the combination of proton beam with photon radiation has the potential to enhance dose distribution, possibly leading to better outcomes for patients.

What evidence suggests that proton beam therapy might be an effective treatment for chordoma?

Research has shown that proton beam therapy, one of the treatments studied in this trial, effectively treats skull base chordoma, a type of tumor. Studies have found that it controls the tumor well over the long term. Compared to standard photon radiation, proton therapy may improve survival rates, though it carries a higher risk of brain tissue damage. In this trial, some participants will receive proton beam therapy alone, while others will receive a combination of proton and photon therapies. Combining proton and photon therapies can enhance treatment effectiveness by delivering a better dose to the tumor. Overall, both treatment options in this trial have shown promise in managing chordomas. ^{3 4 5 6 7}

Who Is on the Research Team?

David R. Grosshans

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with a confirmed diagnosis of chordoma at the base of the skull, who have had surgery to remove as much of the tumor as possible. They should be able to perform daily activities without significant assistance (Karnofsky Performance status ≥60) and must not have had previous radiation therapy in that area or any other cancer (except skin cancer) in the past three years.

Inclusion Criteria

I've had a detailed brain scan within the last 3 months.

Signed informed consent

My cancer is a confirmed chordoma located at the base of my skull.

Exclusion Criteria

I have not had any cancer other than non-melanoma skin cancer in the last 3 years.

I have had radiation therapy on the base of my skull.

My cancer has spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive proton beam therapy once a day for about 35 treatments over 7 weeks, possibly combined with photon beam therapy

7 weeks

35 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with annual follow-up till disease progression or death

1 year

Annual visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Photon Beam Therapy
• Proton Beam Therapy

Trial Overview The study is examining whether proton beam therapy alone or combined with photon beam radiation therapy can effectively treat skull base chordoma. The research will also assess how safe these treatments are for patients.

How Is the Trial Designed?

Group I: Photon Beam Therapy Experimental Treatment 2 Interventions

Proton beam therapy combined with photon radiation therapy where combination improves final dose distribution.

Group II: 70 Gray (Gy) Proton Beam Therapy Experimental Treatment 1 Intervention

Participants treated to 70 cobalt Gray equivalent (CGE) only (the standard treatment).

Proton Beam Therapy is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Proton Beam Therapy for:

• Various cancers including prostate, breast, lung, liver, and head and neck cancers

Approved in European Union as Proton Therapy for:

• Various cancers including ocular melanoma, chordomas, chondrosarcomas, and certain pediatric cancers

Approved in Japan as Proton Beam Therapy for:

• Various cancers including prostate, liver, and ocular melanoma

Approved in Canada as Proton Therapy for:

• Various cancers including ocular melanoma and certain pediatric cancers

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

A study of 48 children with malignant brain tumors treated with proton beam therapy (PBT) showed that acute toxicities were generally low-grade and manageable, with fatigue, alopecia, and dermatitis being the most common side effects.

The research indicates that PBT is well tolerated in pediatric patients, and acute toxicities can be effectively managed with supportive care, suggesting a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity of proton beam radiation for pediatric central nervous system malignancies. Suneja, G., Poorvu, PD., Hill-Kayser, C., et al.[2013]

Proton beam therapy (PBT) shows potential benefits for treating certain cancers, such as pediatric CNS tumors and large ocular melanomas, but current evidence does not support its superiority over traditional photon-based therapies for most other cancer types.

The American Society of Radiation Oncology (ASTRO) recommends further robust clinical trials to better define the appropriate use of PBT, as existing data is insufficient to endorse its routine application in many malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evidence based review of proton beam therapy: the report of ASTRO's emerging technology committee. Allen, AM., Pawlicki, T., Dong, L., et al.[2018]

Proton beam therapy (PBT) is feasible for treating infants with central nervous system tumors, showing promising short-term outcomes with a 3-year overall survival rate of 76.5% among 51 infants studied.

However, the treatment is associated with significant logistical challenges and potential for higher-grade toxicities, including late effects like endocrinopathy and hearing loss, highlighting the need for careful monitoring and longer follow-up to assess long-term impacts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study. Jazmati, D., Steinmeier, T., Ahamd Khalil, D., et al.[2021]

Proton beam therapy (PBT) usage in the US increased from 0.4% in 2004 to 1.2% in 2018, particularly among patients with cancers recommended for PBT by the American Society of Radiation Oncology, indicating growing acceptance and application of this treatment.

While PBT use for prostate cancer temporarily decreased from 2011 to 2014, it rebounded by 2018, suggesting fluctuations in treatment preferences or insurance coverage that may influence patient access to this advanced therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Proton Beam Therapy Use Among Patients With Newly Diagnosed Cancer in the US, 2004-2018. Nogueira, LM., Jemal, A., Yabroff, KR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11274426/

Systematic Review and Meta-Analysis of Particle Beam ... [Objective] The aim of this study was to compare the efficacy of particle beam therapy (PT) with photon radiotherapy (RT) for treatment of skull base chordoma.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2331518023001968

Clinical Outcomes Following Dose-Escalated Proton ... To evaluate the effectiveness of external-beam proton therapy (PT) on local control and survival in patients with skull-base chordoma. Materials and Methods.

3. thejns.org thejns.org/view/journals/j-neurosurg/142/1/article-p239.xml

Impact of proton versus photon adjuvant radiotherapy on ... Although adjuvant proton therapy was found to be superior to adjuvant photon radiotherapy in the treatment of spinal chordomas, this benefit was ...

4. advancesradonc.org advancesradonc.org/article/S2452-1094(24)00019-8/fulltext

A Prospective Phase I/II Clinical Trial of High-Dose Proton ... Chordomas of the spine and sacrum chordomas showed improved actuarial outcomes compared with chordomas of the base of skull within our cohort.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11625079/

Proton beam and carbon ion radiotherapy in skull base ... Both PBT and CIRT are effective treatments for skull base chordoma, with comparable long-term efficacy.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36813169/

Clinical outcomes and toxicities of 100 patients treated with ... Conclusions: In our series, PBT achieved excellent safety and efficacy outcomes with very low rates of treatment failure. CNS necrosis is exceedingly low (<1%) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2452109424001453

Impact of Dosimetric Compromises on Early Outcomes ... With a median follow-up of 27.5 months, 2-year local control and progression-free survival was 86.7% and 81.8% for chordomas and 87.5% and 77.1% for ...