Proton Therapy for Rectal Cancer Recurrence

(IMPARC Trial)

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

15 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this trial is to determine the maximum tolerated dose (MTD) of hypofractionated IMPT for the reirradiation of locoregionally 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 data supports the idea that Proton Therapy for Rectal Cancer Recurrence is an effective treatment?

The available research does not provide specific data on Proton Therapy for Rectal Cancer Recurrence. However, it does show that Proton Therapy, specifically Intensity-modulated Proton Therapy (IMPT), is being explored for other cancers like pancreatic, prostate, head and neck, and anal cancers. In these cases, Proton Therapy has been compared to other treatments and has shown potential benefits, such as lower side effects and improved targeting of cancer cells. This suggests that Proton Therapy could be effective for rectal cancer recurrence as well, but more specific research would be needed to confirm this. ^{1 2 3 4 5}

What safety data is available for proton therapy in treating rectal cancer recurrence?

The safety data for proton therapy, including techniques like Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT), is primarily derived from studies on other cancers such as pancreatic, prostate, and anal cancers. These studies suggest that IMPT can improve the therapeutic ratio by better targeting tumors while sparing healthy tissue, potentially reducing acute and late toxicities. However, specific safety data for rectal cancer recurrence is not directly available in the provided research, indicating a need for further studies in this specific context. ^{1 4 6 7 8}

Is Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy a promising treatment for rectal cancer recurrence?

Yes, Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) is promising because it allows for better dose distribution, which means it can target cancer cells more precisely while sparing healthy tissue. This makes proton therapy more accessible and potentially more effective for patients. ^{2 3 5 6 9}

Research Team

Allen Mo, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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. * 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. * 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. * 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+

Findings from Research

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]

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]

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]

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 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 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 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]

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]

References

1. United States 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. [2022]

2. United States 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. [2018]

3. England 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Hematologic Toxicity Comparison of Intensity Modulated Proton Therapy and Intensity Modulated Radiation Therapy in Anal Cancer Patients. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. [2020]

6. Australia pubmed.ncbi.nlm.nih.gov

Extreme hypofractionated proton radiotherapy for prostate cancer using pencil beam scanning: Dosimetry, acute toxicity and preliminary results. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Intensity modulated proton therapy. [2018]

8. United States 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. [2023]

9. Ireland pubmed.ncbi.nlm.nih.gov

Helical tomotherapy and intensity modulated proton therapy in the treatment of early stage prostate cancer: a treatment planning comparison. [2018]