Hypofractionated Radiotherapy for Endometrial Cancer

Recruiting at 3 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

Trial Summary

What is the purpose of this trial?

This study will investigate if a shorter treatment course (known as "hypofractionation") for pelvic radiation is safe for women with endometrial cancer. Doctors leading the study will also determine the safest and most tolerable dose of shortened radiation (hypofractionation) used to treat women in this study. Because this study will shorten the radiation course typically used to treat endometrial cancer, each daily treatment given to women in this study will be slightly higher than normal to ensure that the total radiation dose they receive is still effective and similar to the radiation dose they would receive if they were not participating in this study (standard treatment).

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 data supports the effectiveness of the treatment Hypofractionated Radiotherapy for Endometrial Cancer?

Research shows that hypofractionated radiotherapy has been effective in providing symptom relief for various advanced pelvic cancers, including rectal and ovarian tumors, with acceptable side effects. Additionally, similar treatments have shown promise in improving outcomes for other cancers like prostate and lung cancer, suggesting potential benefits for endometrial cancer as well. ^{1 2 3 4 5}

Is hypofractionated radiotherapy generally safe for humans?

Hypofractionated radiotherapy has been studied for conditions like prostate and breast cancer, and it is generally considered safe, though it may cause some short-term side effects. Long-term safety data from large trials suggest it does not significantly increase late side effects compared to traditional methods. ^{6 7 8 9 10}

How is hypofractionated radiotherapy different from other treatments for endometrial cancer?

Hypofractionated radiotherapy for endometrial cancer involves giving fewer, larger doses of radiation over a shorter period, which can reduce the treatment burden for patients compared to traditional radiation schedules. This approach has been effective in other cancers, like breast cancer, and may offer similar benefits for endometrial cancer, although it hasn't been extensively studied in this specific condition yet. ^{1 2 11 12 13}

Research Team

Christina Son, MD

Principal Investigator

University of Chicago

Eligibility Criteria

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 18 years old or older.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

References

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

Hypofractionated radiotherapy for the palliation of advanced pelvic malignancy. [2019]

2. United States 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. [2023]

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

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

A review of hypofractionated palliative radiotherapy. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Hypofractionation for prostate cancer: an update. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

What are the minimal standards of radiotherapy planning and dosimetry for "hypofractionated" radiotherapy in breast cancer? [2018]

8. Ireland pubmed.ncbi.nlm.nih.gov

Acute and late toxicity patterns of moderate hypo-fractionated radiotherapy for prostate cancer: A systematic review and meta-analysis. [2023]

9. England 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. [2021]

10. England 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. [2022]

11. India pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy in carcinoma cervix IIIB: Tata Memorial Hospital experience. [2018]

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

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

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

Vaginal brachytherapy alone: an alternative to adjuvant whole pelvis radiation for early stage endometrial cancer. [2018]