Radiation Therapy for Metastatic Cancer

Recruiting at 4 trial locations

Overseen By James Welsh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Immunotherapy

Disqualifiers: Scleroderma, Lupus, Active infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 30

Duration: 4 days to 3 weeks

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of radiation therapy for individuals whose cancer has metastasized and worsened after immunotherapy. The researchers aim to determine the optimal radiation dose and understand any side effects. The trial uses external beam radiation therapy, which targets cancer cells with high-energy beams. It may suit those whose cancer has spread and who did not improve with previous immunotherapy but have treatable areas with radiation. As a Phase 2 trial, it focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you may continue with maintenance immunotherapy while receiving radiation.

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

Research has shown that external beam radiation therapy (EBRT) is generally safe for individuals with metastatic cancer. Studies indicate that EBRT often relieves symptoms, though it may not always prevent cancer growth in the same area. It is also used to address bone issues in cancer patients.

For stereotactic body radiation therapy (SBRT), research has found it effective and well-tolerated. One study showed that individuals with certain cancers experienced positive outcomes with few side effects. Another study found that SBRT was safe and helped delay the need for more intensive treatments.

Both EBRT and SBRT offer benefits with manageable risks. Most patients experience relief and only minor side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this radiation therapy approach for metastatic cancer because it offers a more personalized and potentially quicker treatment option compared to traditional methods. Unlike standard radiation therapy, which might require a longer treatment period, this study employs Stereotactic Body Radiation Therapy (SBRT) and External Beam Radiation Therapy (EBRT) in a flexible range of doses and durations, allowing oncologists to tailor the treatment to individual patient needs. This adaptability could lead to faster, more targeted results, potentially improving patient outcomes and quality of life by reducing treatment time and focusing radiation precisely on cancerous sites.

What evidence suggests that this trial's radiation therapy treatments could be effective for metastatic cancer?

This trial will compare External Beam Radiation Therapy (EBRT) and Stereotactic Body Radiation Therapy (SBRT) for managing metastatic cancer. Research has shown that EBRT can help manage cancer that has spread by easing symptoms and reducing the risk of bone problems in patients with solid tumors. In one study, 62% of patients felt better after receiving EBRT aimed at their cancer spread. Meanwhile, SBRT shows promise, with up to 89.1% success in controlling cancer in the treated area and significantly improving survival chances over two years. SBRT has been effective for various cancers, including those that have spread to the liver and lungs. Both EBRT and SBRT are non-invasive treatments that aim to control cancer growth and improve patient outcomes. Participants in this trial will receive either EBRT or SBRT, as determined by the treating radiation oncologist. ^{3 5 6 7 8}

Who Is on the Research Team?

James Welsh

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with metastatic cancer that has grown despite immunotherapy. They must have a cancer diagnosis, be able to consent, and continue standard care if needed. Participants should have at least one tumor suitable for radiation and an ECOG performance status of 0-2. Women of childbearing age need a recent negative pregnancy test.

Inclusion Criteria

I can keep getting my regular immune therapy while I have radiation treatment.

Note: if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

My cancer diagnosis was confirmed through lab tests.

Exclusion Criteria

I've had radiation therapy in the last 3 months where the treatment areas might overlap.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I have lasting side effects from treatment that are not severe or have been managed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo either 4, 5, or 10 fractions of SBRT, or 5-15 fractions of EBRT to any site of metastatic disease daily for any time between 4 days and 3 weeks as determined by the treating radiation oncologist.

4 days to 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Follow-up at 30 days, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• External Beam Radiation Therapy
• Stereotactic Body Radiation Therapy

Trial Overview The study tests the effectiveness and optimal dose of radiation therapy (Stereotactic Body Radiation Therapy or External Beam Radiation Therapy) in controlling metastatic cancers after progression on immunotherapy. It also involves laboratory biomarker analysis to understand treatment impact.

How Is the Trial Designed?

Group I: Treatment (SBRT or EBRT) Experimental Treatment 3 Interventions

Patients undergo either 4, 5, or 10 fractions of SBRT, or 5-15 fractions of EBRT to any site of metastatic disease daily for any time between 4 days and 3 weeks as determined by the treating radiation oncologist. Patients with at least SD after the second imaging evaluation may undergo additional SBRT in 4 fractions or EBRT in 3 fractions.

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

Approved in European Union as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in United States as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Canada as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Japan as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in China as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Switzerland as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Artidis

Industry Sponsor

Trials

5

Recruited

600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 3 trial involving 1532 prostate cancer patients, escalating the dose of external beam radiation therapy (EBRT) from 70.2 Gy to 79.2 Gy did not significantly impact patient-reported outcomes (PROs) such as erectile function and quality of life over 24 months.

Despite the higher radiation dose, there was no significant difference in the rates of erectile dysfunction between the two treatment groups, indicating that higher doses of EBRT may not lead to worse patient experiences in terms of these specific outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life Implications of Dose-Escalated External Beam Radiation for Localized Prostate Cancer: Results of a Prospective Randomized Phase 3 Clinical Trial, NRG/RTOG 0126. Hall, WA., Deshmukh, S., Bruner, DW., et al.[2023]

In a study of 32 patients receiving External Beam Radiotherapy (EBRT) for bone metastases, 41% experienced a pain flare, which is defined as a significant increase in pain or analgesia intake, with a median duration of 3 days.

The incidence and duration of pain flare observed in this study align with findings from international studies, indicating that pain flare is a common side effect of EBRT for bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigation into the incidence of pain flare in patients undergoing radiotherapy for symptomatic bone metastases. Goldfinch, R., White, N.[2018]

In a study of 31 patients with non-metastatic castration-resistant prostate cancer treated with definitive external-beam radiotherapy (EBRT), the 5-year overall survival rate was 74.6%, indicating that EBRT can lead to favorable long-term survival outcomes.

The treatment resulted in a local relapse-free survival rate of 91% at both 5 and 8 years, suggesting that EBRT is effective in preventing local recurrence of the cancer, although about one-third of patients experienced disease recurrence within 5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of definitive external-beam radiotherapy for non-metastatic castration-resistant prostate cancer. Aizawa, R., Takayama, K., Nakamura, K., et al.[2022]

Patients with asymptomatic bone metastases who received external beam radiation therapy (EBRT) experienced a significant delay in the onset of moderate-to-severe pain and skeletal-related events (SREs), with a median time of 81 months compared to 25 months for untreated patients (P<0.001).

EBRT was particularly effective in delaying pain and SREs in prostate and lung cancer patients, although it did not show the same benefit for breast cancer patients, and it did not affect overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiation therapy (EBRT) for asymptomatic bone metastases in patients with solid tumors reduces the risk of skeletal-related events (SREs). Shulman, RM., Meyer, JE., Li, T., et al.[2020]

External-beam radiotherapy (EBRT) has been effectively used for over 30 years to treat prostate adenocarcinoma, demonstrating significant improvements in cause-specific survival and freedom from PSA progression.

Recent advancements in radiation techniques have enhanced the safety and efficacy of EBRT, making it a viable treatment option for early-stage, locally advanced, and metastatic prostate cancer, while managing side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External-beam radiotherapy in the management of carcinoma of the prostate. Zlotecki, RA.[2017]

In a study of 15,494 newly diagnosed metastatic prostate cancer patients, external beam radiation therapy (EBRT) did not improve overall mortality for the entire group, but it significantly reduced mortality in M1a patients and M1b patients with PSA levels of 10.0 ng/ml or lower.

The findings suggest that only a smaller subset of North American metastatic prostate cancer patients benefit from EBRT compared to previous reports from European studies, highlighting the need for further validation in North America.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiation therapy improves survival in low-volume metastatic prostate cancer patients: a North American population-based study. Stolzenbach, LF., Deuker, M., Collà-Ruvolo, C., et al.[2021]

In a study of 29 patients with oligometastatic hormone-sensitive prostate cancer treated with external beam radiation therapy (EBRT) and androgen deprivation therapy, the median overall survival was 9.7 years, indicating promising long-term outcomes for this treatment approach.

Patients with de novo metastases experienced significantly better progression-free survival (2.0 years) compared to those with oligorecurrent disease (1.8 years), suggesting that the timing and nature of metastases may influence treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Patients on a Phase II Prospective Trial of Oligometastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation and External Beam Radiation. Hao, C., Ladbury, C., Lyou, Y., et al.[2022]

The American Society for Radiation Oncology has released updated, evidence-based guidelines for using external-beam radiotherapy (EBRT) to treat painful bone metastases, emphasizing the importance of these guidelines in improving patient care and quality indices at radiotherapy centers.

Recent findings highlight the need for proper management of pain flare reactions that can occur after starting radiotherapy, as well as the validation of the EORTC QLQ-BM22 quality-of-life module for assessing patient well-being in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent important developments in the management of nonspine bone metastases. Zeng, L., Lutz, S., Chow, E., et al.[2012]

From 2015 to 2017, short-course external-beam radiation therapy (EBRT) for bone metastases increased, while long-course EBRT decreased by 8%, indicating a shift towards more efficient treatment options.

Stereotactic body radiation therapy (SBRT) usage rose to 7% of treatments, showing a growing acceptance of complex techniques, although expenditures for these advanced modalities decreased, suggesting improved cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in Radiation Therapy for Bone Metastases, 2015 to 2017: Choosing Wisely in the Era of Complex Radiation. Santos, PMG., Lapen, K., Zhang, Z., et al.[2022]

External beam radiotherapy (EBRT) is an effective treatment for relieving symptoms caused by bone metastases in prostate cancer patients.

This review specifically compares the effectiveness of single fraction radiotherapy to multiple fraction radiotherapy, highlighting the need for further analysis on which approach may provide better outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single fraction radiotherapy versus multiple fraction radiotherapy for bone metastases in prostate cancer patients: comparative effectiveness. Yoon, F., Morton, GC.[2020]

Definitive external beam radiotherapy (EBRT) for unresectable soft-tissue sarcomas shows promising 5-year local control rates of 28-73% for photon therapies and 52-69% for particle therapies, based on a systematic review of 29 studies involving 1409 patients.

While doses of 64-66 Gy appear to be safe and effective, higher doses (≥68 Gy) significantly increase the risk of severe adverse events, highlighting the need for careful dose management in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a place for definitive radiotherapy in the treatment of unresectable soft-tissue sarcoma? A systematic review. Allignet, B., Sunyach, MP., Geets, X., et al.[2022]

A pilot study involving seven patients found that while traditional education methods for external beam radiation therapy (EBRT) were satisfactory, 86% of participants felt they did not fully capture the treatment experience.

The introduction of a 360-degree virtual reality (VR) video as a supplemental educational tool showed potential benefits, including improved understanding of the treatment process and reduced anxiety, especially when viewed before the first treatment session.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Learning in 360 Degrees: A Pilot Study on the Use of Virtual Reality for Radiation Therapy Patient Education. Johnson, K., Liszewski, B., Dawdy, K., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9012312/

Technological Advancements in External Beam Radiation ... Recent technological advancements have increased the efficacy of radiotherapy, leading to effective management of cancer patients with enhanced patient ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3298009/

Cancer and Radiation Therapy: Current Advances and ... There are two ways to deliver radiation to the location of the cancer. External beam radiation is delivered from outside the body by aiming high-energy rays ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1879850025000979

Combination Metastasis-Targeted External Beam ... Most patients (n = 32/52; 62%) had symptom relief following M-EBRT. Symptom relief post–M-EBRT was 68%, 85%, and 50%, and mortality rates were ...

4. apm.amegroups.org apm.amegroups.org/article/view/22241/html

External beam radiation therapy (EBRT) for asymptomatic ... External beam radiation therapy (EBRT) for asymptomatic bone metastases in patients with solid tumors reduces the risk of skeletal-related events (SREs)

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.330

Real-world clinical outcomes of patients with localized ... Results: Of 11,127 LPC pts treated with EBRT within 6 months of LPC diagnosis, ~40% (n=4,414) were HRLPC and ~60% (N=6,713) were LIRLPC. Patient ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12512287/

Study protocol: feasibility and safety of conventional ... Conventional external beam radiotherapy (EBRT) provides effective symptom relief, but local progression remains frequent. Stereotactic body ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.106

Safety outcomes in patients with metastatic castration ... We evaluated safety outcomes in patients with mCRPC treated with Ra-223 following external beam radiation therapy (EBRT) in the US.

8. urotoday.com urotoday.com/conference-highlights/asco-gu-2024/asco-gu-2024-prostate-cancer/149309-asco-gu-2024-safety-outcomes-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-radium-223-following-external-beam-radiation-therapy-reassure-us-subset.html

ASCO GU 2024: Safety Outcomes in Patients with ... The primary endpoint was overall survival and patients receiving radium-223 had significantly improved median overall survival (14.9 versus 11.3 ...