Proton Therapy for Breast Cancer

(COMPRO Trial)

Recruiting at 4 trial locations

Overseen By Edith Maritato

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Proton Collaborative Group

Disqualifiers: Inflammatory breast cancer, Metastatic disease, Connective tissue disorder, BRCA mutation, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

Duration: 3-5 weeks

276 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Proton Therapy for Breast Cancer?

Research shows that intensity-modulated proton therapy (IMPT) can reduce radiation exposure to the heart in breast cancer patients, especially those with cancer on the left side. Additionally, studies report positive outcomes for women treated with IMPT after mastectomy, suggesting it may be effective in managing breast cancer while minimizing harm to nearby organs. ^{1 2 3 4 5}

Is proton therapy generally safe for humans?

Proton therapy, including techniques like intensity-modulated proton therapy (IMPT), has been studied for various cancers, including breast and pancreatic cancer. These studies suggest that proton therapy can reduce radiation exposure to healthy tissues, potentially leading to fewer side effects compared to traditional radiation methods, indicating it is generally safe for humans. ^{1 4 5 6 7}

How is proton therapy different from other treatments for breast cancer?

Proton therapy for breast cancer is unique because it reduces radiation exposure to the heart and lungs compared to traditional radiation methods, which is especially beneficial for patients with left-sided breast cancer or those requiring internal mammary chain irradiation. ^{1 2 8 9 10}

What is the purpose of this trial?

The purpose of this research study is to learn more about the effects of using proton radiation therapy delivered over a shorter course of treatment (3 weeks) compared with a longer, standard course of treatment (5 weeks) for women with breast cancer who require radiotherapy to the breast/chest wall and regional lymph nodes.

Research Team

Isabelle Choi, MD

Principal Investigator

Proton Collaborative Group

Eligibility Criteria

This trial is for women with Stage I-III breast cancer who've had surgery or need postoperative radiation to the breast/chest and lymph nodes. They must have no distant metastases, be in good physical condition (ECOG 0-2), not pregnant, and able to start treatment within 12 weeks of surgery/chemo. Breast reconstruction and bilateral cancer are okay if at least one side gets full nodal irradiation.

Inclusion Criteria

I have had a physical exam within the last 90 days.

I have breast implants, expanders, tissue flaps, or other forms of breast reconstruction.

My breast cancer diagnosis is confirmed and requires radiation therapy including to the chest and lymph nodes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive proton radiation therapy with either a hypofractionated approach over 3 weeks or a standard fractionation over 5 weeks

3-5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-related skin and soft tissue toxicities

2 years

Long-term Follow-up

Assessment of patient-reported quality of life and physician-reported cosmetic outcomes

10 years

Treatment Details

Interventions

• Proton Therapy

Trial Overview The study compares two ways of delivering proton radiation therapy: a shorter course over 3 weeks versus a standard longer course over 5 weeks. It aims to understand the effects on women needing radiotherapy after breast cancer surgery.

Participant Groups

Group I: Arm B - Hypofractionation Experimental Treatment 1 Intervention

40.05 Gy (RBE) in 15 daily fractions of 2.67 Gy (RBE) plus a Tumor Bed Boost (for intact breast) of 10 Gy (RBE) in 4-5 daily fractions of 2-2.5 Gy (RBE) \*\*Additional boost of 10-20 Gy (RBE) in 2-2.5 Gy (RBE) fractions to clinically involved lymph nodes or chest wall/scar allowed at the treating physician's discretion\*\*

Group II: Arm A - Standard Fractionation Active Control 1 Intervention

50-50.4 Gy (RBE) in 25-28 daily fractions of 1.8-2.0 Gy (RBE) plus a Tumor Bed Boost (for intact breast) of 10 Gy (RBE) in 4-5 daily fractions of 2-2.5 Gy (RBE) \*\*Additional boost of 10-20 Gy (RBE) in 2-2.5 Gy (RBE) fractions to clinically involved lymph nodes or chest wall/scar allowed at the treating physician's discretion\*\*

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

Approved in United States as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Approved in European Union as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Approved in Canada as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Approved in Japan as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Who Is Running the Clinical Trial?

Proton Collaborative Group

Lead Sponsor

Trials

10

Recruited

41,100+

Findings from Research

Intensity-modulated proton therapy (IMPT) shows similar target coverage and dose distribution quality compared to volumetric-modulated arc therapy (VMAT) in a study of 20 breast cancer patients, indicating its efficacy as a treatment option.

IMPT significantly reduces the estimated risk of secondary cancer induction (EAR) in contralateral organs compared to VMAT, suggesting a safer profile for patients undergoing regional nodal irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential Role of Intensity-modulated Proton Therapy in the Regional Nodal Irradiation of Breast Cancer: A Treatment Planning Study. De Rose, F., Cozzi, L., Meattini, I., et al.[2020]

In a study of 14 left-sided breast cancer patients, intensity modulated proton therapy (IMPT) significantly reduced radiation doses to cardiac substructures compared to volumetric modulated arc therapy (VMAT), indicating a safer treatment option for minimizing cardiac exposure.

The most exposed cardiac area was the mid segment of the left anterior descending coronary artery, and the study suggests that mean heart dose (MHD) may not be a reliable measure for evaluating cardiac exposure when using IMPT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac substructure exposure in breast radiotherapy: a comparison between intensity modulated proton therapy and volumetric modulated arc therapy. Loap, P., Tkatchenko, N., Goudjil, F., et al.[2022]

In a study of 127 women treated with intensity modulated proton therapy (IMPT) after mastectomy, the five-year locoregional control rate was an impressive 98.4%, indicating high effectiveness in preventing cancer recurrence.

Patient-reported outcomes showed minimal significant changes in quality of life metrics, with only slight increases in skin color and itchiness, suggesting that IMPT is associated with manageable side effects and good overall patient satisfaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmastectomy Intensity Modulated Proton Therapy: 5-Year Oncologic and Patient-Reported Outcomes. Gao, RW., Mullikin, TC., Aziz, KA., et al.[2023]

Intensity modulated proton therapy (IMPT) for inflammatory breast cancer (IBC) was well-tolerated in a study of 19 patients, with a median follow-up of 24 months showing no locoregional recurrences and overall survival and distant metastasis-free survival rates of 89% and 82%, respectively.

The treatment demonstrated excellent dosimetry with low rates of adverse events, including only 11% experiencing acute grade 3 dermatitis and 21% with rib fractures, indicating that IMPT is a safe and effective option for IBC management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton therapy for the treatment of inflammatory breast cancer. Fattahi, S., Mullikin, TC., Aziz, KA., et al.[2022]

The Spot-scanning proton arc (SPArc) therapy significantly reduced radiation exposure to critical organs like the heart and lungs in patients undergoing left-sided whole breast radiotherapy, with heart dose reduced from 110.38 cGy to 53.63 cGy and lung dose from 25.56% to 16.77%.

SPArc therapy demonstrated better plan robustness and a significant reduction in the risk of normal tissue complications compared to conventional intensity-modulated proton therapy (vIMPT), making it a promising technique for improving patient safety during breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study: spot-scanning proton arc therapy (SPArc) for left-sided whole breast radiotherapy. Chang, S., Liu, G., Zhao, L., et al.[2021]

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) significantly reduces radiation doses to organs at risk (OARs) compared to both intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in left-sided breast cancer patients, based on a study of 20 patients.

IMPT provides better target coverage while minimizing low doses to the left lung and heart, with reductions of over 2.5 times for lung doses and over 20 times for cardiac doses compared to IMRT, suggesting it may lower the risk of late toxicity in patients requiring complex-target irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative proton radiotherapy for localized and locoregional breast cancer: potential for clinically relevant improvements? Ares, C., Khan, S., Macartain, AM., et al.[2022]

Intensity-modulated proton therapy (IMPT) techniques for treating bilateral breast cancer (BBC) showed excellent target coverage, achieving over 95% coverage for the prescribed dose, similar to volumetric modulated arc therapy (VMAT).

IMPT significantly reduced the radiation dose to critical organs at risk, such as the heart and lungs, with a mean heart dose of only 2.12 Gy compared to 9.98 Gy with VMAT, highlighting its potential for safer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Techniques for Treating Bilateral Breast Cancer Patients Using Pencil Beam Scanning Technology. Vyfhuis, MAL., Zhu, M., Agyepong, B., et al.[2022]

Intensity modulated proton therapy (IMPT) offers improved dose delivery and better sparing of non-target tissues compared to traditional 3D conformal radiation therapy in women with bilateral breast implants after mastectomy, based on a study involving 5 patients.

IMPT achieved similar target coverage while significantly reducing mean doses to the heart and lungs, suggesting it may allow for effective radiation therapy without delaying breast reconstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated proton therapy for postmastectomy radiation of bilateral implant reconstructed breasts: a treatment planning study. Jimenez, RB., Goma, C., Nyamwanda, J., et al.[2013]

Proton pencil beam scanning (PBS) therapy significantly reduces the risk of secondary cancers in breast cancer patients compared to traditional photon therapies, with a notable reduction in risk for younger patients with nodal involvement.

In a study involving 10 breast cancer patients, PBS showed a lower cumulative excess absolute risk for secondary cancers in the lungs and contralateral breast compared to tangential 3D-CRT and VMAT, highlighting its potential as a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton pencil beam scanning reduces secondary cancer risk in breast cancer patients with internal mammary chain involvement compared to photon radiotherapy. Cartechini, G., Fracchiolla, F., Menegotti, L., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

The Potential Role of Intensity-modulated Proton Therapy in the Regional Nodal Irradiation of Breast Cancer: A Treatment Planning Study. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Cardiac substructure exposure in breast radiotherapy: a comparison between intensity modulated proton therapy and volumetric modulated arc therapy. [2022]

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

Postmastectomy Intensity Modulated Proton Therapy: 5-Year Oncologic and Patient-Reported Outcomes. [2023]

4. Ireland pubmed.ncbi.nlm.nih.gov

Proton therapy for the treatment of inflammatory breast cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Feasibility study: spot-scanning proton arc therapy (SPArc) for left-sided whole breast radiotherapy. [2021]

6. 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]

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

Postoperative proton radiotherapy for localized and locoregional breast cancer: potential for clinically relevant improvements? [2022]

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

Techniques for Treating Bilateral Breast Cancer Patients Using Pencil Beam Scanning Technology. [2022]

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

Intensity modulated proton therapy for postmastectomy radiation of bilateral implant reconstructed breasts: a treatment planning study. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Proton pencil beam scanning reduces secondary cancer risk in breast cancer patients with internal mammary chain involvement compared to photon radiotherapy. [2021]