Hypofractionated Radiotherapy for Endometrial Cancer

Recruiting at 4 trial locations

Overseen By Christina Son, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: University of Chicago

Must not be taking: Chemotherapy

Disqualifiers: Metastases, Gross residual disease, 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: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation therapy to women with endometrial cancer. Instead of the usual extended course, the study examines a shorter, more intense treatment schedule, known as hypofractionated radiation, to assess its safety and effectiveness. The trial consists of two parts: determining the right dose and evaluating its effectiveness. Women who have undergone surgery to remove their cancer and have no remaining cancer cells are suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have chemotherapy at the same time as the study. It's best to discuss your specific medications with the trial team.

What prior data suggests that hypofractionated radiotherapy is safe for women with endometrial cancer?

Research has shown that hypofractionated radiation, which involves delivering a shorter but stronger dose of radiation, appears promising for patients with endometrial cancer. Studies have found that patients generally tolerate this treatment well. Specifically, research with uterine cancer patients demonstrated that they experienced few serious side effects. This suggests it could be a safe option for those considering participation in a clinical trial. However, as the current study is in its early stages, it focuses on identifying the safest dose, and additional data will help confirm its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about hypofractionated radiation for endometrial cancer because it offers a potentially quicker and equally effective treatment compared to the traditional, longer radiation schedules. Unlike standard radiation therapy, which typically spans several weeks, this approach condenses the treatment into just 3-5 weeks, which can be more convenient for patients. Additionally, by finding a safe and tolerable dose in a shorter timeframe, it aims to maintain or even enhance the effectiveness of treating endometrial cancer while minimizing the burden on patients' schedules.

What evidence suggests that hypofractionated radiation might be an effective treatment for endometrial cancer?

Research has shown that a shorter course of radiation treatment, known as hypofractionated radiation, can effectively treat endometrial cancer. In this trial, participants in the Dose-Finding Arm will receive hypofractionated whole pelvic radiation to determine a safe and tolerable dose. Once established, participants in the Expansion Cohort will assess the efficacy of this shortened treatment. Studies have found that this shorter treatment can control cancer as effectively as standard, longer treatments. Specifically, one study reported that patients who received the shorter radiation course had a 59% chance of being disease-free after five years. This suggests that hypofractionated radiation might be as effective as traditional longer treatments for managing cancer. Additionally, this type of radiation has been successfully used in other gynecologic cancers, indicating potential effectiveness for endometrial cancer as well. ^{1 2 4 6 7}

Who Is on the Research Team?

Christina Son, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for women over 18 with Stage I-III endometrial cancer who've had a hysterectomy and show no signs of remaining cancer or distant metastases. It's not for those receiving concurrent chemotherapy, with bowel issues, prior pelvic radiation, unresolved chemo side effects, or connective tissue disorders.

Inclusion Criteria

My diagnosis is endometrial cancer with a specific cell type.

I am advised to have pelvic radiotherapy alone, not with chemotherapy.

My cancer was diagnosed as Stage I-III by FIGO standards.

Exclusion Criteria

I have a history of bowel issues or connective tissue disorder needing ongoing treatment, or I've had pelvic radiation.

I am not currently undergoing any chemotherapy.

I still have cancer cells after surgery, confirmed by my doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Hypofractionated Radiation Treatment (Dose-Finding Arm)

Participants receive hypofractionated whole pelvic radiation treatment for a shortened time period to establish a safe and tolerable dose.

3-5 weeks

Expansion Cohort (Efficacy Arm)

Participants test the efficacy of the established dose of hypofractionated radiation treatment.

3-5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with routine clinical follow-up approximately 1 month following radiation, then at 3 months, and every 3 months for the next 2 years.

2 years

Routine clinical follow-up at 1 month, 3 months, and every 3 months thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionated Radiation

Trial Overview The study tests if a shorter course of higher-dose pelvic radiation (hypofractionation) is safe and effective in treating endometrial cancer compared to the standard longer treatment. The goal is to find the best dose that's both tolerable and similar in effectiveness to conventional therapy.

How Is the Trial Designed?

Group I: Hypofractionated Radiation Treatment (Dose-Finding Arm) Experimental Treatment 1 Intervention

All study participants in this arm will receive hypofractionated whole pelvic radiation treatment for a shortened time period of 3-5 weeks. The goal of this arm is to establish a safe and tolerable dose of shortened (hypofractionated) pelvic radiation treatment for study participants. Once a safe and tolerable dose is established for this shortened form of radiation treatment, participants who meet criteria for the second phase of this study will participate in an expansion cohort that will explore the efficacy (how effective shortened/hypofractionated radiation treatment is for treating endometrial cancer).

Group II: Expansion Cohort (Efficacy Arm) Experimental Treatment 1 Intervention

Participants in this arm will test how effective hypofractionated/shortened whole radiation treatment is ("efficacy") at the dose established in the first phase of this study by following up with their doctors to report their current health status and symptoms during clinical visits. Participants will return for routine clinical follow-up approximately 1 month following radiation, then at 3 months following radiation, then every 3 months for the next 2 years following treatment.

Hypofractionated Radiation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hypofractionated Radiotherapy for:

• Endometrial cancer

Approved in European Union as Hypofractionated Radiotherapy for:

• Endometrial cancer
• Cervical cancer

Approved in Canada as Hypofractionated Radiotherapy for:

• Endometrial cancer

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a study of 41 patients with high-risk localized prostate cancer, combining whole-pelvis irradiation with a stereotactic body radiotherapy (SBRT) boost resulted in a high 4-year biochemical failure-free survival rate of 91.9%, indicating effective cancer control.

The treatment was associated with minimal toxicity, with no severe (grade 3) gastrointestinal or genitourinary side effects reported, suggesting that this approach is safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The early result of whole pelvic radiotherapy and stereotactic body radiotherapy boost for high-risk localized prostate cancer. Lin, YW., Lin, LC., Lin, KL.[2020]

In a study of 39 breast cancer patients treated with an accelerated hypofractionated radiotherapy schedule, no significant lung toxicity or adverse effects were observed after a median follow-up of 43 months, indicating the treatment's safety.

The radiotherapy regimen (34 Gy in 10 fractions plus an 8 Gy boost) was well-tolerated, with only minor skin changes noted in a few patients, suggesting it is a feasible option for adjuvant treatment without significant long-term side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated hypofractionated radiotherapy as adjuvant regimen after conserving surgery for early breast cancer: interim report of toxicity after a minimum follow up of 3 years. Pinnarò, P., Soriani, A., Landoni, V., et al.[2021]

In a study of 62 women with advanced cervical cancer treated with hypofractionated radiotherapy, the 5-year disease-free survival rate was 59% and overall survival was 50%, indicating that this treatment can be effective for advanced cases.

While some patients experienced acute gastrointestinal and genitourinary complications, most reactions were mild (grade I or II), suggesting that hypofractionated radiotherapy is a safe option for patients with extensive local disease who may not be suitable for standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy in carcinoma cervix IIIB: Tata Memorial Hospital experience. Muckaden, MA., Budrukkar, AN., Tongaonkar, HB., et al.[2018]

A study involving 42 patients with advanced pelvic cancers showed that a hypofractionated radiotherapy regimen (30 Gy in three fractions) provided effective symptom relief with manageable side effects.

The treatment was particularly effective for patients with advanced rectal and ovarian tumors, indicating potential benefits for these specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy for the palliation of advanced pelvic malignancy. Hodson, DI., Malaker, K., McLellan, W., et al.[2019]

Hypofractionated radiotherapy is gaining popularity for breast cancer treatment in the UK and Canada, but there are concerns about potential increased toxicity associated with this approach.

The article emphasizes the importance of careful planning and dosimetry in hypofractionated radiotherapy to ensure effective treatment while minimizing risks, and it provides recommendations for both planning and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What are the minimal standards of radiotherapy planning and dosimetry for "hypofractionated" radiotherapy in breast cancer? MacLeod, N., McIntyre, A., Canney, PA.[2018]

Moderate hypofractionated radiotherapy for prostate cancer is associated with a 6.3% increase in acute grade ≥ 2 gastrointestinal toxicity compared to standard fractionation, indicating a need for careful monitoring and management of these symptoms.

There was no significant increase in acute genitourinary toxicity or late toxicity levels between moderate hypofractionation and standard fractionation, suggesting that while acute GI symptoms may be more common, overall safety profiles for late effects are similar.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and late toxicity patterns of moderate hypo-fractionated radiotherapy for prostate cancer: A systematic review and meta-analysis. Sinzabakira, F., Brand, V., Heemsbergen, WD., et al.[2023]

Hypofractionated radiation therapy, which delivers fewer but larger doses of radiation over a shorter period, has shown comparable outcomes to conventional radiation in treating breast cancer, suggesting it could be an effective alternative.

Ongoing phase 3 trials are investigating hypofractionated whole breast irradiation and accelerated partial breast irradiation, which may lead to broader acceptance of these methods for early-stage breast cancer, although concerns about patient selection and late toxicity remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation therapy in the treatment of early-stage breast cancer. Freedman, GM.[2021]

In a phase 1/2 trial involving 61 patients with uterine cancer, stereotactic hypofractionated radiation therapy was found to be well tolerated, with most patients experiencing only mild to moderate acute gastrointestinal and genitourinary toxic effects.

While some patients reported significant diarrhea during treatment, this symptom improved after follow-up, indicating that the short-term quality of life impact may be manageable, but longer-term studies are necessary to fully assess the treatment's safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-of-Life Outcomes and Toxic Effects Among Patients With Cancers of the Uterus Treated With Stereotactic Pelvic Adjuvant Radiation Therapy: The SPARTACUS Phase 1/2 Nonrandomized Controlled Trial. Leung, E., Gladwish, AP., Davidson, M., et al.[2023]

Hypofractionated radiation therapy (HypoRT) was found to be effective in treating inoperable advanced non-small cell lung cancer (NSCLC), with an overall response rate of 83% among 30 patients, and a median follow-up of 13 months.

The treatment was well-tolerated, with manageable acute toxicities; however, 37% of patients experienced locoregional recurrence, and 57% developed distant metastasis, indicating the need for further studies to compare HypoRT with conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. Osti, MF., Agolli, L., Valeriani, M., et al.[2018]

Postoperative hypofractionated high dose rate (HDR) vaginal brachytherapy (VB) for early stage endometrial adenocarcinoma resulted in a low local recurrence rate of 4% and a 2-year cumulative recurrence rate of 2%, comparable to the Gynecologic Oncology Group (GOG)-99 trial results.

HDR VB demonstrated significantly lower chronic toxicity rates, particularly gastrointestinal toxicity (0% vs. 34% in pelvic radiation therapy), while achieving similar overall survival rates (97% in our study vs. 92% in GOG-99 pelvic RT arm).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal brachytherapy alone: an alternative to adjuvant whole pelvis radiation for early stage endometrial cancer. Jolly, S., Vargas, C., Kumar, T., et al.[2018]

Recent evidence suggests that hypofractionated radiotherapy for prostate cancer is both safe and effective, particularly with a recommended regimen of 60 Gy in 20 fractions, which showed no significant increase in late toxicity.

While moderate hypofractionation has demonstrated positive 5-year outcomes in large trials, further research is needed for extreme hypofractionation techniques, and their use should currently be restricted to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionation for prostate cancer: an update. Tiberi, D., Vavassis, P., Nguyen, D., et al.[2019]

In a phase 3 trial involving 804 patients with localized prostate cancer, hypofractionated radiotherapy showed a 5-year relapse-free survival rate of 80.5%, which was not significantly better than the 77.1% rate for conventionally fractionated radiotherapy, indicating no superiority in treatment outcomes.

Both treatment regimens were found to be safe, with no treatment-related deaths reported, suggesting that while hypofractionation is not superior, it does not increase the risk of severe adverse effects compared to conventional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial. Incrocci, L., Wortel, RC., Alemayehu, WG., et al.[2022]

Hypofractionated palliative radiotherapy, which can involve as few as one to fourteen treatment sessions, is effective in providing symptom relief for patients with painful bony metastasis and various primary cancers, offering similar relief to longer treatment courses.

This treatment approach is time-efficient, cost-effective, and minimally toxic, yet there is a noted reluctance among radiation oncologists to use single-fraction treatments, highlighting the need for better collaboration between radiation oncologists and palliative care professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of hypofractionated palliative radiotherapy. Lutz, ST., Chow, EL., Hartsell, WF., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04683653

Study of Pelvic Hypofractionated Radiotherapy in ... This study will investigate if a shorter treatment course (known as "hypofractionation") for pelvic radiation is safe for women with endometrial cancer.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS5631

RT-PACE: Phase I/II study of adjuvant whole pelvic ... Background: Whole pelvic radiation therapy (WPRT) improves locoregional control in women with high-intermediate and high-risk endometrial ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10814353/

Hypofractionated Radiotherapy in Gynecologic ... Radiotherapy (RT) has a fundamental role in the treatment of gynecologic malignancies, including cervical and uterine cancers. Hypofractionated ...

4. ejgo.org ejgo.org/Synapse/Data/PDFData/1114JGO/jgo-37-e4.pdf

Postoperative conventional versus A recent study on ultra- hypofractionation, which administered 30 Gy in 5 fractions to patients with endometrial cancer using stereotactic body ...

5. withpower.com withpower.com/trial/phase-endometrial-neoplasms-2021-b18c3

Hypofractionated Radiotherapy for Endometrial Cancer In a study of 62 women with advanced cervical cancer treated with hypofractionated radiotherapy, the 5-year disease-free survival rate was 59% and overall ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9011178/

Quality-of-Life Outcomes and Toxic Effects Among Patients ... Meaning. These results suggest that stereotactic hypofractionated radiation to the pelvis is well tolerated among patients with uterine cancer ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11467485/

Evidence-based clinical recommendations for ... Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/β ratio compared with conventional fractionation RT.