Proton vs Photon Radiation for Retroperitoneal Sarcoma

Recruiting at 10 trial locations

Overseen By Thomas DeLaney, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Massachusetts General Hospital

Must not be taking: Chemotherapy, Antiretrovirals, others

Disqualifiers: Prior radiation, Pregnancy, Metastases, others

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

Compensation: Varies

Number of Visits: 7

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of radiation therapy, proton beam and IMRT, to determine the highest safe dose for treating retroperitoneal sarcomas, which are tumors deep in the abdomen. Proton radiation targets more precisely, potentially reducing side effects compared to traditional methods. Participants will receive radiation before surgery to evaluate which method is more effective. This trial suits individuals diagnosed with retroperitoneal sarcoma who have not previously received radiation treatment for it. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have had chemotherapy within 4 weeks before the study or are receiving other investigational agents.

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

Previous research has shown that proton radiation therapy is safe. One study found that higher doses of proton therapy before surgery were safe and helped control tumor growth. Proton therapy targets tumors more precisely, potentially leading to fewer side effects compared to other radiation types.

For IG-IMRT, a type of radiation treatment, studies have shown it is generally well-tolerated. The FDA has approved this treatment for some cancers, indicating it has been tested for safety in other conditions. IG-IMRT focuses radiation on the tumor while protecting nearby healthy tissue.

Both proton therapy and IG-IMRT are being tested to determine the best safe dose for people with retroperitoneal sarcomas, a type of tumor in the abdomen. While both treatments have been used safely in other cases, this study aims to confirm their safety specifically for these tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for retroperitoneal sarcoma because they offer innovative approaches to radiation therapy. IG-IMPT (Intensity-Guided Intensity-Modulated Proton Therapy) uses proton beams, which can precisely target tumors while sparing surrounding healthy tissues more effectively than traditional photon radiation. This precision reduces potential side effects and damage to nearby organs. On the other hand, IG IMRT (Intensity-Guided Intensity-Modulated Radiation Therapy) also offers highly targeted radiation but uses photons. Both methods aim to improve outcomes by focusing radiation on high-risk areas, potentially leading to better control of the cancer with fewer side effects compared to conventional radiation therapies.

What evidence suggests that this trial's treatments could be effective for retroperitoneal sarcoma?

Research has shown that proton beam therapy, one of the treatments in this trial, can more accurately target tumors and protect healthy tissue. This precision may lead to fewer side effects compared to traditional radiation. Proton therapy for similar tumors has resulted in less damage to nearby organs. In contrast, IG-IMRT, the other treatment option in this trial, has been associated with better survival rates for some cancers. The chance of avoiding cancer recurrence with these therapies can reach up to 69% over five years. Both methods show promise in effectively treating retroperitoneal sarcomas while minimizing harm to healthy tissues. ^{2 3 6 7 8}

Who Is on the Research Team?

Thomas DeLaney, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for people with a life expectancy over 2 years who have measurable, histologically confirmed primary soft tissue sarcoma in the retroperitoneum. It's not for those previously treated with radiation for this condition, pregnant or breastfeeding individuals, patients on other investigational drugs, those with multifocal disease or metastases, sensitivity to radiation therapy, HIV on anti-retrovirals, uncontrolled illnesses, recent chemotherapy recipients within 4 weeks prior to the study start date.

Inclusion Criteria

My cancer is a type of sarcoma that started in the tissue behind my stomach.

Life expectancy of greater than 2 years

My cancer can be measured by tests.

Exclusion Criteria

History of sensitivity to radiation therapy

My cancer has spread to lymph nodes or other parts of my body.

I am HIV positive and on combination anti-retroviral therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Radiation Therapy

Participants receive proton beam radiation therapy or IMRT with a simultaneously integrated boost to high-risk areas of the tumor

6 weeks

5 visits per week (in-person)

Pre-Surgery Assessment

Participants are assessed for side effects of radiation and undergo imaging and blood tests before surgery

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery, with follow-up visits scheduled within one month and four months post-surgery, then twice yearly for five years, and annually thereafter

Long-term

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• IG-IMPT
• IG IMRT

Trial Overview The study tests two FDA-approved radiation therapies: proton beam therapy (IG-IMPT) and IMRT before surgery to remove retroperitoneal sarcomas. The goal is to find the safest high dose of these radiations that can be given by targeting most of the tumor and giving an extra boost to higher risk areas.

How Is the Trial Designed?

Group I: Treatment Arm IMRT Experimental Treatment 1 Intervention

IG IMRT with SIB to the high risk margin

Group II: Treatment Arm IMPT Experimental Treatment 1 Intervention

IG-IMPT with SIB to the high risk margin

IG-IMPT is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Proton Therapy for:

• Various cancers including but not limited to prostate cancer, brain tumors, spinal tumors, and soft tissue sarcomas like retroperitoneal sarcomas

Approved in European Union as Proton Therapy for:

• Various cancers including but not limited to ocular tumors, brain tumors, and soft tissue sarcomas

Approved in Japan as Proton Therapy for:

• Various cancers including but not limited to prostate cancer, brain tumors, and ocular tumors

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Rush University Medical Center

Collaborator

Trials

448

Recruited

247,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Roswell Park Cancer Institute

Collaborator

Trials

427

Recruited

40,500+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

Pencil-beam scanning intensity modulated proton therapy (IMPT) for localized pancreatic cancer showed significant reductions in radiation exposure to surrounding organs at risk, such as the small bowel and liver, compared to volumetric modulated arc therapy (VMAT).

No patients experienced severe (grade ≥3) treatment-related adverse events, and there was no significant change in health-related quality of life scores during treatment, indicating that IMPT is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with intensity modulated proton therapy for intact, clinically localized pancreas cancer: Clinical implementation, dosimetric analysis, acute treatment-related adverse events, and patient-reported outcomes. Jethwa, KR., Tryggestad, EJ., Whitaker, TJ., et al.[2022]

Proton therapy (PT), especially intensity modulated proton therapy (IMPT), shows superior treatment planning for prostate cancer by providing better homogeneity in the planning target volume (PTV) and sparing surrounding healthy tissues, such as the rectum, compared to traditional intensity-modulated radiation therapy (IMRT).

Proton therapy significantly reduces the dose to normal tissues outside the PTV, exposing them to less than 50% of the dose delivered by IMRT, making it a promising option for prostate cancer treatment in Australian facilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of proton therapy and IMRT treatment plans for prostate radiotherapy. Dowdell, SJ., Metcalfe, PE., Morales, JE., et al.[2019]

Intensity-modulated proton therapy (IMPT) was found to irradiate only half the tissue volume with a lower dose compared to intensity-modulated x-ray therapy (IMXT), which could reduce the risk of secondary cancers and complications.

Both treatment plans were effective in covering target volumes for patients with advanced prostate carcinoma, indicating that IMPT can be a safer alternative without compromising treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LOW DOSE BATH FROM IMPT VS. IMXT FOR THE PELVIC AREA WHEN TREATING ADVANCED PROSTATE CANCER. Navrátil, M., Vondráček, V., Andrlík, M., et al.[2020]

A dosimetric comparison of pre-operative ultra-hypofractionated intensity-modulated proton therapy (IMPT) and photon therapy (IMRT) in 10 patients with retroperitoneal sarcoma showed that IMPT significantly reduced radiation exposure to surrounding organs at risk, such as the liver and gastrointestinal tract.

IMPT maintained effective coverage of the target area while minimizing the overall radiation dose compared to IMRT, suggesting it could be a safer option for patients undergoing pre-operative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative In Silico Analysis of Ultra-Hypofractionated Intensity-Modulated Photon Radiotherapy (IMRT) Versus Intensity-Modulated Proton Therapy (IMPT) in the Pre-Operative Treatment of Retroperitoneal Sarcoma. Gogineni, E., Chen, H., Istl, AC., et al.[2023]

In a study involving eight patients with retroperitoneal or intra-abdominal sarcomas, both intensity-modulated proton therapy (3DCPT) and intensity-modulated photon therapy (IMRT) provided better conformity and homogeneity in radiation delivery compared to 3D conformal photon therapy (3DCRT).

Proton therapy (3DCPT) showed a significant reduction in radiation exposure to surrounding healthy tissues, particularly the bowel and kidneys, suggesting it may lead to lower gastrointestinal and genitourinary toxicity compared to IMRT and 3DCRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of three-dimensional (3D) conformal proton radiotherapy (RT), 3D conformal photon RT, and intensity-modulated RT for retroperitoneal and intra-abdominal sarcomas. Swanson, EL., Indelicato, DJ., Louis, D., et al.[2022]

In a phase 1 trial involving 11 patients with retroperitoneal sarcoma, intensity modulated proton therapy (IMPT) successfully escalated the radiation dose to 63 GyRBE without causing acute dose limiting toxicities, indicating a promising safety profile for higher doses.

After 18 months of follow-up, there were no local recurrences of the tumor, suggesting that the IMPT approach may effectively reduce the risk of local recurrence in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of preoperative image guided intensity modulated proton radiation therapy with simultaneously integrated boost to the high risk margin for retroperitoneal sarcomas. DeLaney, TF., Chen, YL., Baldini, EH., et al.[2020]

Intensity modulated proton therapy (IMPT) significantly reduces the integral dose to organs at risk (OAR) compared to intensity modulated photon therapy (IMPT), with reductions in mean doses to the heart, lungs, kidneys, stomach, and liver by factors ranging from 1.3 to 25.

Both IMPT and IM photon therapy provide optimal tumor coverage, but IMPT allows for dose escalation to the tumor without exceeding normal tissue dose limits, enhancing treatment efficacy while maintaining safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A treatment planning comparison of intensity modulated photon and proton therapy for paraspinal sarcomas. Weber, DC., Trofimov, AV., Delaney, TF., et al.[2022]

Intensity modulated radiation therapy (IMRT) significantly improved tumor coverage for retroperitoneal sarcomas, increasing the percentage of the tumor receiving the prescribed dose from 95.3% with 3D-conformal treatment to 98.6% with IMRT.

IMRT also reduced the mean dose to surrounding organs at risk, such as the small bowel, from 36 Gy to 27 Gy, while maintaining effective treatment, suggesting it is a safer and more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated radiation therapy for retroperitoneal sarcoma: a case for dose escalation and organ at risk toxicity reduction. Koshy, M., Landry, JC., Lawson, JD., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.11550

Preliminary results of phase 2 trial of preoperative image ... Image-guided intensity modulated radiation therapy (IG-IMRT) affords increased survival for biliary tract tumors: Results from preliminary ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9795731/

Neoadjuvant radiotherapy for resectable retroperitoneal ... High local recurrence rates (> 50%) and low overall survival rates (40%-60%) have been major challenges for clinicians in managing patients with ...

3. cco.amegroups.org cco.amegroups.org/article/view/59082/html

A critical narrative review of radiotherapy for retroperitoneal ... The local failure-free survival rate at 5 years was 69%. AdjRT significantly improved LC compared to no radiation treatment (HR =0.42, 95% CI: ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01659203

Proton or Photon RT for Retroperitoneal Sarcomas The purpose of this study is to determine the highest dose of radiation therapy with protons or IMRT that can be delivered safely in patients with ...

5. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-022-02072-9

Preoperative hypofractionated radiotherapy for soft tissue ... Overall, LC as a quality criterion for HFRT shows good to excellent results, ranging between 80–100% between 3 to 5 years in the largest studies ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06327477?tab=table

Proton-Spatially Fractionated Radiotherapy and Standard ... Patients undergo P-SFRT over 1 fraction and then undergo image-guided intensity modulated radiation therapy (IG-IMRT) over 25-28 fractions for 35 to 42 days.

7. withpower.com withpower.com/trial/phase-2-sarcoma-11-2012-44cd4

Proton vs Photon Radiation for Retroperitoneal Sarcoma The purpose of this study is to determine the highest dose of radiation therapy with protons or IMRT that can be delivered safely in patients with ...

8. astro.org astro.org/ASTRO/media/ASTRO/Daily%20Practice/PDFs/IMRTMP.pdf

Model Policies IMRT treatment plans are tailored to target volumes and are geometrically more accurate than conventional, two- dimensional or three-dimensional conformal ...