Proton Therapy for Rectal Cancer Recurrence

(IMPARC Trial)

No longer recruiting at 1 trial location

Overseen By Hyun Kim

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: Radiosensitizing conditions, Other malignancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating rectal cancer that has returned in the pelvic area after previous treatment. The focus is on determining the optimal dose of hypofractionated IMPT (Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy), which targets cancer more precisely. Participants will receive one of several doses to identify the most effective and safe option. This trial suits individuals whose rectal cancer has returned in the pelvis after one course of radiation therapy and who can manage their daily activities. As an unphased trial, it offers participants the chance to contribute to pioneering research that could lead to new treatment options for recurrent rectal cancer.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot be on any investigational agents.

What prior data suggests that hypofractionated IMPT is safe for reirradiation of locoregionally recurrent rectal cancer?

Research has shown that hypofractionated pencil-beam scanning intensity-modulated proton therapy (IMPT) is generally manageable for patients. Studies have found that proton therapy often causes fewer side effects than traditional radiation treatments due to its ability to target tumors more precisely, thereby protecting healthy tissues.

Some studies report that patients may experience mild side effects like skin irritation or tiredness, but serious side effects are less common. The current trial focuses on determining the highest dose patients can tolerate without major issues, emphasizing safety as a top priority.

This type of proton therapy has been used for other conditions, providing insight into its safety. While more data is always beneficial, early results are promising regarding patient tolerance. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) for rectal cancer recurrence because it offers precision and potential speed. Unlike traditional radiotherapy, which often involves longer treatment times with broader radiation exposure, IMPT uses a pencil-beam scanning technique that precisely targets cancer cells while sparing surrounding healthy tissue. This precision may reduce side effects and improve patient well-being. Additionally, the hypofractionated approach delivers higher doses of radiation over fewer sessions, potentially leading to quicker treatment outcomes.

What evidence suggests that hypofractionated IMPT could be an effective treatment for recurrent rectal cancer?

Studies have shown that proton therapy can effectively treat recurrent rectal cancer. This trial evaluates different dose levels of Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) to find the most effective approach. This therapy uses protons to target cancer cells more precisely than regular radiation, potentially leading to fewer side effects. Research indicates that proton therapy controls tumors as effectively as conventional radiation but may cause less harm to nearby healthy tissues. The treatment uses a focused beam of radiation shaped to match the tumor's exact size and shape. Initial findings suggest it might be especially beneficial for patients requiring a second round of radiation. ^{4 5 6 7 8}

Who Is on the Research Team?

Michael Waters, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults who've had one round of radiation for rectal cancer and now have a recurrence in the pelvis. They must be generally fit (ECOG 0-2), able to consent, and use birth control if needed. Excluded are those with more than one prior pelvic radiation, other active cancers or serious illnesses, pregnant/breastfeeding women, or certain genetic conditions.

Inclusion Criteria

My cancer in the rectum, anus, or rectosigmoid junction has come back in the pelvis.

I can take care of myself and perform daily activities.

Able to understand and willing to sign an IRB-approved written informed consent document.

Exclusion Criteria

I had cancer before, but it was treated over 2 years ago and I'm now cancer-free, or it was a minor skin cancer or cervical condition treated locally.

I do not have any ongoing infections or heart issues.

I have conditions like lupus or genetic mutations that make my tissues more sensitive to radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive hypofractionated IMPT for reirradiation of locoregionally recurrent rectal cancer, consisting of five fractions delivered once daily

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of quality of life and clinical response

12 months

Multiple visits at 1-2 weeks, 3, 6, 9, and 12 months post-radiation therapy

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT)

Trial Overview The study tests how much of a new type of targeted proton therapy called hypofractionated IMPT can be given safely to treat recurrent rectal cancer. It uses advanced technology like MEVION S250i Hyperscan to deliver precise doses while minimizing damage to healthy tissue.

How Is the Trial Designed?

Group I: Dose Level 3: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) Experimental Treatment 2 Interventions

* Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 3 (40 Gy). * The use of Intensity Modulated Radiation Therapy (IMRT) with photon beam therapy is permitted at the discretion of the treating investigator in order to avoid extended treatment delays due to logistical reasons (e.g. machine downtime).

Group II: Dose Level 2: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) Experimental Treatment 2 Interventions

* Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 2 (35 Gy). * The use of Intensity Modulated Radiation Therapy (IMRT) with photon beam therapy is permitted at the discretion of the treating investigator in order to avoid extended treatment delays due to logistical reasons (e.g. machine downtime).

Group III: Dose Level 1: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) Experimental Treatment 2 Interventions

* Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 1 (30 Gy). * The use of Intensity Modulated Radiation Therapy (IMRT) with photon beam therapy is permitted at the discretion of the treating investigator in order to avoid extended treatment delays due to logistical reasons (e.g. machine downtime).

Group IV: Dose Level -1: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) Experimental Treatment 2 Interventions

* Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level -1 (25 Gy). * The use of Intensity Modulated Radiation Therapy (IMRT) with photon beam therapy is permitted at the discretion of the treating investigator in order to avoid extended treatment delays due to logistical reasons (e.g. machine downtime).

Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) is already approved in United States, Japan, European Union for the following indications:

Approved in United States as Proton Therapy for:

• Colorectal cancer
• Prostate cancer
• Liver cancer
• Esophageal cancer
• Pancreatic cancer

Approved in Japan as Proton Therapy for:

• Colorectal cancer
• Prostate cancer
• Liver cancer
• Esophageal cancer
• Pancreatic cancer

Approved in European Union as Proton Therapy for:

• Colorectal cancer
• Prostate cancer
• Liver cancer
• Esophageal cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

In a study of 41 anal cancer patients treated with either intensity modulated proton therapy (IMPT) or intensity modulated radiation therapy (IMRT), IMPT resulted in lower doses to pelvic bone marrow and active bone marrow, suggesting a potential for reduced toxicity.

Despite the lower radiation doses to bone marrow with IMPT, there was no significant difference in hematologic toxicity between the two treatment groups, indicating that IMPT may not lead to fewer severe blood-related side effects compared to IMRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematologic Toxicity Comparison of Intensity Modulated Proton Therapy and Intensity Modulated Radiation Therapy in Anal Cancer Patients. Nelson, B., Tadesse, DG., Sudhoff, M., et al.[2023]

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]

In a study involving 200 patients with early-stage prostate cancer, extreme hypofractionated proton therapy (36.25 GyE in five fractions) demonstrated feasibility with a low rate of acute toxicity, where no patients experienced severe (G3) side effects.

After a median follow-up of 36 months, the treatment showed promising effectiveness, with no local recurrences of cancer and a low PSA relapse rate of 1.08% in low-risk and 6.5% in intermediate-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extreme hypofractionated proton radiotherapy for prostate cancer using pencil beam scanning: Dosimetry, acute toxicity and preliminary results. Kubeš, J., Vondráček, V., Andrlik, M., et al.[2020]

Intensity-modulated photon radiotherapy (IMRT) provided better dose conformity to the prostate cancer target compared to three-dimensional conformal proton therapy (3D-CPT), while both methods effectively delivered the prescribed dose to at least 98% of the target volume.

Proton therapy, particularly with optimized configurations, significantly reduced radiation exposure to the bladder and rectum at lower doses, indicating a potential advantage in sparing healthy tissues during prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. Trofimov, A., Nguyen, PL., Coen, JJ., et al.[2020]

In a study of 56 patients with high-risk prostate cancer, moderately hypofractionated intensity modulated proton therapy (IMPT) showed low rates of late gastrointestinal (GI) toxicity, with only 7.4% experiencing grade ≥2 toxicity after 2 and 3 years, and just 1.9% experiencing grade 3 toxicity.

The study found that 20.5% of patients had late grade ≥2 genitourinary (GU) toxicity at 2 years, increasing to 29.2% at 3 years, but no patients experienced grade 3 GU toxicity, indicating that while GU toxicity was more common, it remained manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late Toxicity of Moderately Hypofractionated Intensity-Modulated Proton Therapy Treating the Prostate and Pelvic Lymph Nodes for High-Risk Prostate Cancer. Choo, R., Hillman, DW., Mitchell, C., et al.[2023]

Intensity-modulated proton therapy (IMPT) provided better target coverage and dose distribution for high-risk prostate cancer patients compared to helical tomotherapy (HT), with over 99% of the planning target volume receiving the prescribed dose in IMPT.

IMPT is expected to reduce rectal toxicity and showed significant dosimetric advantages, with lower radiation exposure to surrounding organs at risk, such as the rectum, bowel, and bladder, compared to HT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Helical tomotherapy vs. intensity-modulated proton therapy for whole pelvis irradiation in high-risk prostate cancer patients: dosimetric, normal tissue complication probability, and generalized equivalent uniform dose analysis. Widesott, L., Pierelli, A., Fiorino, C., et al.[2018]

In a study involving 7 patients with head and neck carcinomas, intensity-modulated proton therapy (IMPT) showed a smaller mean body dose compared to helical tomotherapy (HT), indicating potential benefits in reducing overall radiation exposure.

While HT provided steeper dose gradients and more conformal high dose regions, IMPT demonstrated better normal tissue sparing for specific organs at risk, suggesting that both treatment methods should be considered based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-irradiation of recurrent head and neck carcinomas: comparison of robust intensity modulated proton therapy treatment plans with helical tomotherapy. Stuschke, M., Kaiser, A., Abu-Jawad, J., et al.[2021]

Intensity modulated proton therapy (IMPT) enhances the precision of proton beam delivery, allowing for better targeting of tumors while minimizing damage to surrounding healthy tissue compared to traditional X-ray therapies.

IMPT utilizes the unique Bragg peak of protons to achieve localized dose modulation, which can potentially improve treatment outcomes, but it also presents technical and clinical challenges that need to be addressed for effective implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated proton therapy. Kooy, HM., Grassberger, C.[2018]

In a study involving 8 patients with early-stage prostate cancer, both helical tomotherapy (HT) and intensity modulated proton therapy (IMPT) provided similar coverage and dose homogeneity for the target areas, with 5-field IMPT yielding the best results.

IMPT significantly reduced the radiation dose to surrounding organs at risk (OARs) by 30-50%, particularly sparing the bladder and penile bulb, while maintaining comparable rectal dose levels to HT, suggesting a potential advantage in minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Helical tomotherapy and intensity modulated proton therapy in the treatment of early stage prostate cancer: a treatment planning comparison. Schwarz, M., Pierelli, A., Fiorino, C., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11433675/

Evaluating the Effectiveness of Proton Beam Therapy ... This systematic review seeks to evaluate the radiation dosages and safety of proton beam therapy compared to conventional radiotherapy in ...

2. withpower.com withpower.com/trial/phase-rectal-neoplasms-4-2021-83761

Proton Therapy for Rectal Cancer Recurrence (IMPARC ... The purpose of this trial is to determine the maximum tolerated dose (MTD) of hypofractionated IMPT for the reirradiation of locoregionally recurrent rectal ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0960740421001274

Proton beam therapy in rectal cancer: A systematic review ... This review compares dosimetric irradiation of OAR and oncological outcomes for PBT versus conventional photon-based radiotherapy in locally advanced rectal ...

4. mayo.edu mayo.edu/research/clinical-trials/tests-procedures/proton-therapy

Proton Therapy Clinical Trials The purpose of this study is to evaluate the safety and effectiveness of a moderate hypofractionation regimen of proton beam therapy with same time treatment ...

5. thegreenjournal.com thegreenjournal.com/article/S0167-8140(25)00145-8/fulltext

Linear energy transfer optimized proton therapy for rectal ... LET-optimized proton irradiation is clinically feasible in rectal cancer. Optimizing LET to a volume of GTV-3 mm, or cone down, can further increase LET d.

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/32/NCT04827732/Prot_SAP_002.pdf

Hypofractionated Pencil-Beam Scanning Intensity-modulated ... ... proton therapy to reduce ... therapy in rectal cancer: Results from Intergroup Study 0114. ... Resection of local recurrence of rectal cancer: Results.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04827732

NCT04827732 | Hypofractionated Pencil-Beam Scanning ... The purpose of this trial is to determine the maximum tolerated dose (MTD) of hypofractionated IMPT for the reirradiation of locoregionally recurrent rectal ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12384089/

An In Silico Feasibility Study of Dose-Escalated ... An In Silico Feasibility Study of Dose-Escalated Hypofractionated Proton Therapy for Rectal Cancer · 1. Introduction · 2. Materials and Methods · 3 ...