Tailored Therapy for Endometrial Cancer

Recruiting at 39 trial locations

Overseen by Matthew A Powell

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: NRG Oncology

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

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well tailoring therapy in post-surgery works in patients with low-risk endometrial cancer. The usual approach for patients with low-risk endometrial cancer is treatment with surgery. In this study, tissue that is removed as part of the surgical procedure is analyzed in the pathology laboratory to help guide the doctor to decide whether or not additional treatment such as radiation and or chemotherapy should be recommended.

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.

What data supports the effectiveness of the treatment for endometrial cancer?

Research shows that using external beam radiation therapy (EBRT) and brachytherapy together can effectively control endometrial cancer, especially in cases where surgery isn't an option. Studies indicate that these treatments can achieve high local control rates, meaning they are good at keeping the cancer from growing back in the treated area. ^{1 2 3 4 5}

Is radiation therapy safe for treating endometrial cancer?

Radiation therapy, including external beam radiation therapy (EBRT) and brachytherapy, is generally considered safe for treating endometrial cancer, though it may cause some side effects. Studies have shown that these treatments are feasible and can be used effectively, especially in patients who cannot undergo surgery. ^{1 3 6 7 8}

How does the tailored therapy for endometrial cancer differ from other treatments?

The tailored therapy for endometrial cancer is unique because it involves personalized treatment plans that may include brachytherapy (a type of internal radiation therapy) alone or in combination with external radiation, depending on individual risk factors. This approach is different from standard treatments that often rely on surgery followed by a one-size-fits-all radiation therapy. ^{1 5 9 10 11}

Research Team

Matthew A Powell

Principal Investigator

NRG Oncology

Eligibility Criteria

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

I am 18 years old or older.

Trial Timeline

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)

Treatment Details

Interventions

• Brachytherapy (Brachytherapy)
• External Beam Radiation Therapy (Radiation)

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.

Participant Groups

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+

Stephanie Gaillard

NRG Oncology

Chief Medical Officer

MD from Johns Hopkins University

Norman Wolmark

NRG Oncology

Chief Executive Officer since 2023

MD from Harvard Medical School

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

Dr. Janet Dancey

Canadian Cancer Trials Group

Chief Medical Officer since 2014

MD, FRCPC

Susan Marlin

Canadian Cancer Trials Group

Chief Executive Officer since 2012

BSc (Hons) from Dalhousie University, MSc in Community Health and Epidemiology from Queen’s University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Canadian Cancer Trials Group (CCTG)

Collaborator

Trials

2

Recruited

109,000+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Poland 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Image-guided high-dose-rate brachytherapy in inoperable endometrial cancer. [2022]

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

Definitive radiation therapy for endometrial cancer in medically inoperable elderly patients. [2010]

4. England pubmed.ncbi.nlm.nih.gov

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

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

Radiotherapy practices in postoperative endometrial cancer: A survey of the ABS membership. [2020]

6. Singapore pubmed.ncbi.nlm.nih.gov

Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy for endometrial cancer: a retrospective multicenter study. [2021]

8. Singapore pubmed.ncbi.nlm.nih.gov

External radiation therapy for endometrial carcinoma: the University Hospital of Ioannina experience. [2020]

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

External beam management of stage I and II uterine cancer. [2022]

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

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

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

The role of radiation therapy in the treatment of Stage II endometrial cancer: A large database study. [2019]