Radiation Therapy for Gastrointestinal Cancer

Overseen By Hewitt Chang

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must be taking: Immunotherapy

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Radiation therapy, Immunotherapy trial, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well radiation therapy works for the treatment of gastrointestinal cancer that are spreading to other places in the body (metastatic). Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. This trial is being done to determine if giving radiation therapy to patients who are being treated with immunotherapy and whose cancers are progressing (getting worse) can slow or stop the growth of their cancers. It may also help researchers determine if giving radiation therapy to one tumor can stimulate the immune system to attack other tumors in the body that are not targeted by the radiation therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them as they could affect the immunotherapy.

What data supports the effectiveness of this treatment for gastrointestinal cancer?

Research shows that Intensity-modulated radiation therapy (IMRT) can reduce side effects while effectively targeting tumors in the gastrointestinal system. Intraoperative radiation therapy (IORT) has been found to improve outcomes for patients with difficult-to-treat tumors by delivering radiation directly to the tumor during surgery, minimizing harm to nearby healthy tissues. ^{1 2 3 4 5}

Is radiation therapy generally safe for humans?

Radiation therapy, including advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), has been studied for safety in various conditions. While some patients experience side effects, such as gastrointestinal or genitourinary issues, these techniques are generally considered safe and are used routinely in clinical practice. ^{6 7 8 9 10}

How is radiation therapy unique for treating gastrointestinal cancer?

Radiation therapy for gastrointestinal cancer is unique because it can be precisely targeted to spare healthy tissues while effectively treating tumors, especially with advanced techniques like intensity-modulated radiation therapy (IMRT) and intraoperative radiotherapy (IORT). These methods help reduce side effects and improve local control of the cancer, making them a valuable addition to surgery and chemotherapy. ^{1 3 4 11 12}

Research Team

Mary Feng, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults with metastatic gastrointestinal cancers, including esophageal and colorectal cancers, among others. Participants must have at least two progressing metastases, be on immunotherapy with worsening disease, and have a life expectancy over 6 months. They should not be pregnant or become pregnant during the trial and must use contraception.

Inclusion Criteria

I have seen a radiation oncologist within the last 28 days.

I am mostly self-sufficient and can carry out daily activities.

I have at least two growing cancer spots, and one can be left untreated safely.

Exclusion Criteria

I am not on strong immune system-suppressing drugs that would affect immunotherapy.

My doctor has determined that radiation therapy is not safe for me.

I am in a clinical trial for immunotherapy where radiation is not allowed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo radiation therapy for a total of 5 treatments over 5-9 calendar days in the absence of disease progression or unacceptable toxicity.

1-2 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

Visits at 14 days, 6 months, and then up to 36 months

Treatment Details

Interventions

• Radiation Therapy

Trial Overview The study tests if radiation therapy can slow down or stop the growth of spreading gastrointestinal tumors in patients already receiving immunotherapy. It also explores whether radiating one tumor might activate the immune system to fight other non-radiated tumors.

Participant Groups

Group I: Radiation therapy (RT) Experimental Treatment 1 Intervention

Patients undergo radiation therapy for a total of 5 treatments over 5-9 calendar days in the absence of disease progression or unacceptable toxicity. Target prescription dose will be 30 Gy in 5 fractions and each treatment site (up to 5) will undergo standard Department-approved treatment planning, quality-assurance, and delivery protocols

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

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Findings from Research

Intensity-modulated radiation therapy (IMRT) is designed to reduce both acute and late toxicities associated with traditional radiation therapy for gastrointestinal tumors, showing promise in sparing healthy organs while effectively targeting tumors.

Preclinical studies indicate that IMRT maintains adequate coverage of tumor targets while minimizing damage to surrounding tissues, but further clinical research is needed to fully establish its role in GI tumor management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy for gastrointestinal tumors. Meyer, JJ., Czito, BG., Willett, CG.[2021]

Intraoperative radiation therapy (IORT) provides a way to deliver higher doses of radiation directly to tumors or high-risk areas during surgery, which can improve local control of gastrointestinal cancers.

This method minimizes damage to surrounding healthy tissues, making it a promising option for patients with unresectable tumors or those at high risk for local recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Radiation Therapy for Gastrointestinal Malignancies. Ritter, AR., Miller, ED.[2023]

Surgery remains the primary treatment for most gastrointestinal cancers, but radiotherapy is increasingly used alongside surgery to enhance local control and improve survival rates.

The abstract discusses the evolving role of radiotherapy in treating gastrointestinal malignancies, including new techniques that are being investigated to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of radiotherapy in the surgical management of gastrointestinal cancer. Mahadevan, A., Carey, D.[2019]

Intraoperative radiotherapy (IORT) is a feasible addition to the treatment of gastrointestinal cancer, achieving over 90% local control of tumors, whether they are primary or recurrent.

The use of electron beam IORT does not interfere with surgical procedures or systemic therapies, making it a safe and effective option in multimodal cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative radiotherapy for gastrointestinal malignancies: contemporary outcomes with multimodality therapy. Calvo, FA., Sole, CV., Marsiglia, H., et al.[2018]

Intensity-modulated radiotherapy (IMRT) significantly improves quality of life (QoL) for patients with head and neck cancers compared to traditional two-dimensional radiotherapy (2DRT) and three-dimensional conformal radiotherapy (3DCRT), particularly in areas like dry mouth and eating-related difficulties.

The review included 14 studies, highlighting that while IMRT shows promise for enhancing QoL, further prospective randomized studies are needed to confirm its benefits and justify the additional resources required for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy versus conventional and 3D conformal radiotherapy in patients with head and neck cancer: is there a worthwhile quality of life gain? Tribius, S., Bergelt, C.[2022]

The phase II RTCMIENDOMETRE trial demonstrated that post-operative intensity-modulated radiation therapy (IMRT) significantly reduced the incidence of acute gastrointestinal (GI) toxicity to 27%, which is below the targeted threshold of 30% for grade 2 or higher adverse events in patients with endometrial cancer.

At the 15-week follow-up, no patients experienced grade 2 or higher GI toxicity, and the prevalence of remaining grade 1 events was less than 20%, indicating that IMRT is a safer option compared to conventional pelvic irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of post operative intensity modulated radiotherapy on acute gastro-intestinal toxicity for patients with endometrial cancer: results of the phase II RTCMIENDOMETRE French multicentre trial. Barillot, I., Tavernier, E., Peignaux, K., et al.[2022]

In a study of 100 prostate cancer patients treated with high-dose intensity-modulated radiotherapy (IMRT) and image-guided treatment (IGRT), acute gastrointestinal (GI) toxicity was observed in 12% and genitourinary (GU) toxicity in 42%, with only 4% experiencing severe GU toxicity (grade 3).

After a median follow-up of 26 months, late toxicity rates were low, with only 1.5% experiencing late GI toxicity and 7.7% experiencing late GU toxicity, indicating that high-dose radiotherapy is both effective and has manageable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer. Guckenberger, M., Ok, S., Polat, B., et al.[2022]

Image-guided radiation therapy (IGRT) has evolved significantly and is now widely used in routine clinical practice, emphasizing the importance of quality and patient safety in its application across various treatment techniques and anatomical sites.

The American Society for Radiation Oncology recommends a comprehensive quality-assurance program and an interdisciplinary team approach to ensure IGRT is performed safely and effectively, highlighting the need for ongoing updates to practice guidelines as technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. Qi, XS., Albuquerque, K., Bailey, S., et al.[2023]

In a study of 421 patients undergoing salvage radiotherapy (SRT) after prostate surgery, the use of advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) significantly reduced the incidence of late gastrointestinal (GI) toxicities to 4.8%.

However, increasing the radiation dose to 68 Gy or more was linked to a higher risk of genitourinary (GU) toxicities, indicating that while advanced techniques can help minimize some side effects, higher doses may still pose risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. Tomita, N., Uchiyama, K., Mizuno, T., et al.[2021]

Prostate cancer patients receiving image-guided radiotherapy (IGRT) experienced significantly less severe acute toxicity, such as urinary frequency, diarrhoea, and fatigue, compared to those who did not receive IGRT, with 23% vs 7% for urinary frequency ≥G3 and 15% vs 3% for diarrhoea ≥G2.

The onset of these toxicities was earlier in the non-IGRT group, indicating that IGRT not only reduces the severity of symptoms but also delays their onset, leading to a more tolerable treatment experience for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. Gill, S., Thomas, J., Fox, C., et al.[2021]

Recent advancements in intradiation techniques have expanded the use of radiation therapy for gastrointestinal cancers, showing benefits in both preoperative and postoperative settings for rectal and rectosigmoid carcinoma.

High-dose external beam irradiation, with or without chemotherapy, has shown promising results for locally advanced pancreatic and gastric cancers, while radiotherapy has also provided long-term control in selected esophageal cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of radiation therapy in gastrointestinal cancer. Weissberg, JB.[2019]

Intensity-modulated radiation therapy (IMRT) allows for precise targeting of cancerous tissues while minimizing damage to surrounding healthy tissues, making it a significant advancement over traditional 3D-conformal radiation therapy.

Early clinical experiences with IMRT in treating gastrointestinal cancers, such as gastric and pancreatic cancers, suggest lower normal tissue toxicities, supporting its efficacy and safety in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of intensity-modulated radiation therapy in gastrointestinal cancer. Bockbrader, M., Kim, E.[2022]

References

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

Intensity-modulated radiation therapy for gastrointestinal tumors. [2021]

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

Intraoperative Radiation Therapy for Gastrointestinal Malignancies. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The role of radiotherapy in the surgical management of gastrointestinal cancer. [2019]

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

Intraoperative radiotherapy for gastrointestinal malignancies: contemporary outcomes with multimodality therapy. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy versus conventional and 3D conformal radiotherapy in patients with head and neck cancer: is there a worthwhile quality of life gain? [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Impact of post operative intensity modulated radiotherapy on acute gastro-intestinal toxicity for patients with endometrial cancer: results of the phase II RTCMIENDOMETRE French multicentre trial. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer. [2022]

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

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. [2021]

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

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. [2021]

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

Role of radiation therapy in gastrointestinal cancer. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Role of intensity-modulated radiation therapy in gastrointestinal cancer. [2022]