Tailored Therapy for Endometrial Cancer

Recruiting at 62 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: NRG Oncology

Disqualifiers: Prior chemotherapy, Prior radiation, Metastasis, Other malignancies, 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

Compensation: Varies

Number of Visits: 1

Duration: 3-5 weeks

325 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether additional treatments, such as radiation or chemotherapy, are necessary for patients with low-risk endometrial cancer after surgery. Typically, surgery serves as the main treatment, but the study examines tailoring further treatment based on detailed lab analysis of the removed tissue. It involves either observation or radiation therapy options, including brachytherapy (internal radiation) and external beam radiation. Patients who have undergone surgery for low-risk endometrial cancer and are willing to undergo further testing and possible additional treatment may be suitable candidates. As a Phase 2 trial, this research measures the effectiveness of the treatment in an initial, smaller group of participants, offering them a chance to contribute to significant advancements in cancer care.

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.

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

Previous studies have shown that brachytherapy safely delivers high doses of radiation by placing radioactive materials close to tumors. This method targets cancer cells while reducing exposure to nearby healthy tissues. Reports suggest that patients generally tolerate brachytherapy well, with fewer severe side effects compared to other radiation treatments.

Research on external beam radiation therapy (EBRT) indicates that it can treat endometrial cancer with minimal risk of severe side effects. EBRT involves directing radiation from outside the body to the cancer area. Studies have found this treatment to be safe and effective.

Overall, both brachytherapy and EBRT have been used safely for treating endometrial cancer, offering targeted treatment with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for endometrial cancer because they offer personalized approaches that consider genetic differences among patients. Unlike traditional treatments, which typically involve surgery and non-specific radiation, this approach uses a combination of brachytherapy and external beam radiation tailored to the patient's genetic profile. For instance, patients with higher-risk POLE-mutated cancer may receive targeted radiation therapy, while those with specific p53 wildtype profiles might be candidates for observational strategies or focused brachytherapy. This customization means that treatments could potentially be more effective and have fewer side effects by honing in on the unique characteristics of each patient's cancer.

What evidence suggests that this trial's treatments could be effective for endometrial cancer?

Research has shown that radiation therapy, including External Beam Radiation Therapy (EBRT) and brachytherapy, can effectively treat endometrial cancer. In this trial, participants in Cohort A2 may receive EBRT and/or vaginal brachytherapy, while those in Sub-study B may receive vaginal brachytherapy. One study found that radiation therapy improved survival rates over 10 years, particularly for patients with higher-risk conditions. Another study discovered that brachytherapy, which involves placing radiation sources inside the body, increased 3-year survival rates by 5% in some endometrial cancer cases. Additionally, brachytherapy successfully stopped vaginal bleeding in 83% of patients. These treatments have been used effectively to manage and improve outcomes for endometrial cancer patients. ^{3 6 7 8 9}

Who Is on the Research Team?

Matthew A Powell

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage I to III endometrial carcinoma who've had surgery with no remaining visible disease. They must be able to complete questionnaires in English, French or another validated language and live close enough to the treatment center for follow-up. Those unwilling to fill out questionnaires or unable to return for follow-ups are excluded.

Inclusion Criteria

My endometrial cancer is confirmed and is stage I to III.

I have signed the consent form to participate in this trial.

I can care for myself and am up and about more than 50% of my waking hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients undergo observation or receive external beam radiation therapy (EBRT) and/or vaginal brachytherapy over 3-5 fractions based on molecular classification

3-5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 3 and 6 months, then every 6 months for 3 years, and then annually

Up to 5 years

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Brachytherapy
• External Beam Radiation Therapy

Trial Overview

The study tests tailored therapy post-surgery in low-risk endometrial cancer patients. It involves analyzing surgically removed tissue to decide if additional treatments like radiation or chemotherapy are needed after surgery.

How Is the Trial Designed?

Group I: Cohort A2 Experimental Treatment 8 Interventions

Patients with higher-risk POLE-mutated EC undergo observation or EBRT and/or vaginal brachytherapy over 3-5 fractions. Patients undergo chest x-ray and CT or MRI or PET/CT scans during screening and as clinically indicated throughout the trial.

Group II: Sub-study B Active Control 7 Interventions

Patients with p53 wildtype/NSMP ER+ EC undergo observation or vaginal brachytherapy over 3-5 fractions. Patients undergo chest x-ray and CT or MRI or PET/CT scans during screening and as clinically indicated throughout the trial.

Group III: Cohort A1 Active Control 6 Interventions

Patients with POLE-mutated early-stage EC undergo observation on study. Patients undergo chest x-ray and CT or MRI or PET/CT scans during screening and as clinically indicated throughout the trial.

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Canadian Cancer Trials Group (CCTG)

Collaborator

Trials

2

Recruited

109,000+

Published Research Related to This Trial

Postoperative external-beam pelvic radiotherapy (EBRT) increases the risk of death in low-risk endometrial cancer patients, suggesting it should not be used for this group.

For high-risk endometrial cancer, EBRT provides a significant disease-free survival advantage, benefiting about 10% of women, while also reducing the risk of pelvic recurrence across all invasive cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival and recurrent disease after postoperative radiotherapy for early endometrial cancer: systematic review and meta-analysis. Johnson, N., Cornes, P.[2022]

In a study of 50 patients with stage I high-intermediate risk endometrial carcinoma, vaginal brachytherapy (VBT) alone showed comparable overall and disease-free survival rates to combined external beam radiotherapy (EBRT) and VBT, with 5-year survival rates of 92% for VBT and 96% for EBRT+VBT.

Patients receiving VBT alone experienced significantly fewer adverse effects, such as dermatological and gastrointestinal toxicities, compared to those receiving the combined treatment, suggesting VBT is a safer option without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined external beam radiotherapy and vaginal brachytherapy versus vaginal brachytherapy in stage I, intermediate- and high-risk cases of endometrium carcinoma. Sunil, RA., Bhavsar, D., Shruthi, MN., et al.[2022]

In a study of 79 patients with early-stage endometrial cancer, the addition of pelvic radiotherapy to brachytherapy (EBRT-BT) resulted in a significant increase in acute toxicities, including a 37% rise in Grade 1-3 diarrhea and a 34% increase in lethargy compared to brachytherapy alone.

Despite the increased acute toxicities associated with EBRT-BT, all reported side effects resolved within three months post-treatment, highlighting the importance of patient counseling regarding potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity. Koh, YV., Tang, JI., Choo, BA., et al.[2020]

A study of 26 elderly women (median age 83) with endometrial cancer who were not surgical candidates showed that definitive radiation therapy, including external beam radiation and brachytherapy, is a feasible and well-tolerated treatment option.

The treatment resulted in an overall survival rate of 89% at 1 year and 73% at 3 years, with only 8% of patients experiencing late toxicity, indicating a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive radiation therapy for endometrial cancer in medically inoperable elderly patients. Wegner, RE., Beriwal, S., Heron, DE., et al.[2010]

High-dose rate electronic brachytherapy (EBT) is a feasible and safe option for postoperative adjuvant radiation therapy in endometrial cancer, with 41 patients treated and no reported recurrences during a median follow-up of 3.8 months.

Adverse events were mostly mild to moderate, with no severe complications in the EBT-only group, indicating a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy for endometrial cancer: a retrospective multicenter study. Dooley, WC., Thropay, JP., Schreiber, GJ., et al.[2021]

Surgical resection, specifically total hysterectomy and bilateral salpingo-oophorectomy, is the primary treatment for early-stage endometrial cancer, with adjuvant radiation therapy used mainly to prevent local recurrence in higher-risk patients.

Vaginal cuff brachytherapy is recommended for high-intermediate risk patients due to its effectiveness and fewer side effects compared to pelvic radiation, while pelvic radiation therapy is reserved for more advanced cases, highlighting the importance of tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam management of stage I and II uterine cancer. Edwards, DM., Jolly, S.[2022]

A survey of 75 responses from 62 centers revealed that 79% of practitioners prefer vaginal vault brachytherapy (VVB) alone for treating FIGO Stage IB, Grade 2 endometrial cancer with negative lymphovascular space invasion, indicating a strong preference for this targeted approach in specific cases.

For more advanced cases, such as FIGO Stage IB, Grade 3 with positive lymphovascular space invasion, there is a tendency to incorporate external beam radiotherapy (EBRT), with 75% recommending a combination of VVB and EBRT for Stage IIIC1, highlighting the variability in treatment strategies based on disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy practices in postoperative endometrial cancer: A survey of the ABS membership. Martell, K., Doll, C., Barnes, EA., et al.[2020]

Brachytherapy is a key treatment option for endometrial cancer, especially in patients who cannot undergo surgery, providing effective local control either alone or in combination with external radiation therapy.

Postoperative intravaginal brachytherapy is the most common application for managing endometrial cancer, tailored based on the patient's pathologic risk factors to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gynecologic brachytherapy-II: Intravaginal brachytherapy for carcinoma of the endometrium. Chadha, M.[2004]

In a study of 31 women with endometrial cancer treated with postoperative external beam radiotherapy (EBRT) alone, the overall survival rate was 97% and disease-free survival was 87% after a median follow-up of 17 months.

The treatment resulted in excellent local control of the cancer, with only one local recurrence and four cases of metastases, although three patients experienced post-radiation colitis as a side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External radiation therapy for endometrial carcinoma: the University Hospital of Ioannina experience. Pakos, EE., Gritzeli, SP., Tsekeris, PG., et al.[2020]

High-dose-rate brachytherapy, particularly when guided by imaging, offers improved local control rates for inoperable endometrial cancer, achieving about 90-100% compared to 70-90% with conventional techniques.

Using image-guided brachytherapy allows for better targeting of the tumor while minimizing radiation exposure to surrounding healthy organs, enhancing the overall effectiveness and safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided high-dose-rate brachytherapy in inoperable endometrial cancer. Dankulchai, P., Petsuksiri, J., Chansilpa, Y., et al.[2022]

A study involving over 8,000 patients with Stage II endometrial cancer found that adjuvant radiation therapy (RT) significantly improves overall survival, with both external beam radiation therapy (EBRT) and brachytherapy (BT) showing benefits.

Brachytherapy alone may be a viable treatment option for carefully selected patients, as it demonstrated comparable survival rates to EBRT, suggesting that it could be sufficient in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of radiation therapy in the treatment of Stage II endometrial cancer: A large database study. Wojcieszynski, AP., Hullett, CR., Medlin, EE., et al.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10863227/

Review of brachytherapy clinical trials - PubMed Central - NIH

Despite these positive outcomes, there seems to be a decrease in brachytherapy use in modern radiation oncology for several cancer types [9–11].

2.

mdpi.com

mdpi.com/2075-4426/14/12/1138

Safety and Efficacy of Brachytherapy in Inoperable ...

Despite these weaknesses, our clinical results are promising. Vaginal bleeding stopped in 83% of patients, and the recurrence rate was 33.3%. It is important to ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1538472121000441

Role of brachytherapy in stage III endometrial cancer ...

In the endometrioid cohort, brachytherapy was associated with a 5% absolute increase in 3-year overall survival (87% vs. 82%, p < 0.0001), which persisted in ...

4.

healthcare.utah.edu

healthcare.utah.edu/huntsmancancerinstitute/press-releases/2025/02/short-course-radiation-therapy-effective-endometrial-cancer-patients

Short-Course Radiation Therapy Effective for Endometrial ...

Short-course, higher dose vaginal brachytherapy for endometrial cancer had similar effectiveness to more frequent, lower dose sessions.

5.

cancerindex.org

cancerindex.org/Brachytherapy

Brachytherapy

This study evaluates the survival and pain relief outcomes of the I-seeds implantation brachytherapy in advanced pancreatic cancer patients.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11676033/

Safety and Efficacy of Brachytherapy in Inoperable ...

The 5-year overall survival (OS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were 51%, 79%, and 69%. The 5-year ...

7.

mayoclinic.org

mayoclinic.org/tests-procedures/brachytherapy/about/pac-20385159

Brachytherapy

The overall treatment time can be shorter with brachytherapy because a larger dose of radiation can be safely delivered at one time. Why it's ...

8.

thegreenjournal.com

thegreenjournal.com/article/S0167-8140(25)04483-4/abstract

Salvage brachytherapy for local recurrence of cancer after ...

Outcomes after definitive re-irradiation with 3D brachytherapy with or without external beam radiation therapy for vaginal recurrence of endometrial cancer.

9.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK562190/

Brachytherapy - StatPearls - NCBI Bookshelf

Brachytherapy (BT) is a radiotherapy technique where radioactive devices are inserted near tumors to safely deliver high doses of radiation to eliminate and ...