Hypofractionated Radiotherapy for Endometrial and Cervical Cancers

(HERA Trial)

Overseen By Christy Palodichuk

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Concurrent chemotherapy, Active malignancy, Prior irradiation, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

Duration: 2 weeks

60 Participants Needed

Trial Summary

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 this treatment for endometrial and cervical cancers?

Research shows that stereotactic ablative radiation therapy (SABR) and stereotactic body radiation therapy (SBRT) have been effective and safe alternatives for cervical cancer patients who cannot undergo traditional brachytherapy, suggesting potential benefits for similar treatments in endometrial and cervical cancers. ^{1 2 3 4 5}

Is hypofractionated radiotherapy generally safe for humans?

Hypofractionated radiotherapy, including stereotactic body radiation therapy (SBRT) and stereotactic ablative radiotherapy (SABR), has been shown to be safe in treating conditions like early-stage lung cancer and low-risk prostate cancer, with studies reporting on long-term safety and patient-reported outcomes. ^{4 6 7 8 9}

How is hypofractionated radiotherapy different from other treatments for endometrial and cervical cancers?

Hypofractionated radiotherapy is unique because it delivers higher doses of radiation in fewer sessions compared to traditional radiation therapy, which can be more convenient and potentially more effective for some patients. It uses advanced techniques like stereotactic body radiation therapy (SBRT) to precisely target tumors, making it a good option for patients who cannot undergo standard brachytherapy. ^{1 2 3 10 11}

What is the purpose of this trial?

After surgery to remove the main endometrial and/or cervical tumor, most women receive radiation therapy. This study uses hypo-fractionated radiation therapy, which is a type of radiation therapy in which the total prescribed dose of radiation is delivered in fewer but larger doses than conventional or standard radiotherapy. This research study aims to determine if hypo-fractionated radiation therapy given after surgery can improve treatment tolerability (i.e., fewer treatments) with comparable side effects. Participants will be in the study for about 5 years: Radiation therapy: * 5 daily treatment sessions of MRI or CT-Guided Stereotactic Body Radiation Therapy (SBRT). * Each treatment session will occur on a weekday (typically consecutive weekdays) and will last approximately an hour. Treatment Follow-Up: * Check-up Appointment and answer questions at 3 months post RT * Check-up Appointments with physical exam every 6 months (+/- 4 weeks) for up to 5 years.

Research Team

Puja S. Venkat, MD

Principal Investigator

University of California at Los Angeles

Eligibility Criteria

This trial is for women who have had surgery to remove endometrial or cervical cancer. They should be candidates for post-surgery radiation therapy and able to undergo MRI or CT scans. Specific details about inclusion and exclusion criteria are not provided, but typically participants must meet certain health standards.

Inclusion Criteria

I can care for myself but may not be able to do active work.

My cancer diagnosis is confirmed for either endometrial or cervical cancer.

I have had surgery to remove my primary tumor.

Exclusion Criteria

I am not required to have chemotherapy as part of my standard treatment.

I am currently being treated for another cancer.

I have had radiation therapy to the area that needs treatment now.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 fractions of MRI or CT-Guided Stereotactic Body Radiation Therapy (SBRT) with adaptive planning, delivered once every other day excluding weekends and holidays

2 weeks

5 visits (in-person)

Initial Follow-up

Participants have a check-up appointment and answer questions at 3 months post-radiotherapy

3 months

1 visit (in-person or virtual)

Long-term Follow-up

Participants have check-up appointments with physical exams every 6 months for up to 5 years post-radiotherapy

5 years

10 visits (in-person or virtual)

Treatment Details

Interventions

• Hypofractionated External Beam Radiotherapy

Trial Overview The study tests hypo-fractionated external beam radiotherapy after surgery in women with endometrial or cervical cancers. This approach uses fewer, larger doses of radiation compared to the standard method, aiming to maintain effectiveness while reducing treatment time.

Participant Groups

Group I: Hypofractionated External beam Radiotherapy Experimental Treatment 1 Intervention

5 daily treatment sessions of MRI or CT-Guided Stereotactic Body Radiation Therapy (SBRT).

Hypofractionated External Beam Radiotherapy is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Hypofractionated External Beam Radiotherapy for:

• Endometrial cancer
• Cervical cancer
• Prostate cancer
• Breast cancer
• Lung cancer

Approved in European Union as Hypofractionated Radiation Therapy for:

• Endometrial cancer
• Cervical cancer
• Prostate cancer
• Breast cancer
• Lung cancer

Approved in Canada as Stereotactic Body Radiation Therapy (SBRT) for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Spine tumors

Approved in Japan as Hypofractionation for:

• Prostate cancer
• Breast cancer
• Lung cancer

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Findings from Research

Stereotactic ablative radiation therapy (SAbR) was assessed as a potential alternative to brachytherapy for patients with locally advanced cervical cancer, but the study faced challenges with safety and efficacy, leading to the closure of the trial after 15 of 21 patients completed it due to toxicity concerns.

The 2-year survival rates were lower than expected, with local control at 70.1% and significant grade ≥ 3 toxicity (26.7%) primarily affecting the rectum, indicating that patient selection and tumor size are critical factors in determining the success of SAbR in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Stereotactic Ablative Radiation Therapy as a Boost for Locally Advanced Cervical Cancer. Albuquerque, K., Tumati, V., Lea, J., et al.[2020]

Stereotactic body radiation therapy (SBRT) using helical tomotherapy (HT) showed a 78% locoregional control rate at 3 years for nine cervical cancer patients who were unsuitable for brachytherapy, indicating its efficacy as a treatment option.

While two patients experienced significant acute toxicity, the overall safety profile was acceptable, with manageable side effects and no severe long-term toxicities reported, suggesting that SBRT via HT is a viable alternative for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy via helical tomotherapy to replace brachytherapy for brachytherapy-unsuitable cervical cancer patients - a preliminary result. Hsieh, CH., Tien, HJ., Hsiao, SM., et al.[2022]

Recent advancements in radiation therapy for cervical cancer, such as intensity-modulated radiation therapy (IMRT) and image-guided brachytherapy (IGBT), are improving local control of the disease while reducing toxicity to normal tissues.

The shift towards IGBT and three-dimensional volume-based prescriptions is leading to better treatment outcomes, and SBRT is emerging as a potential option for patients with limited metastases, although more research is needed to confirm its efficacy in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving from standardized to personalized boxes and pears in radiation planning for cervical cancer. Mesko, S., Kamrava, M.[2015]

Stereotactic ablative body radiotherapy (SABR) boost for cervical cancer patients who cannot undergo brachytherapy showed promising efficacy, with 3-year local control and overall survival rates of 80.9% and 77.1%, respectively, based on a study of 25 patients.

The treatment was generally well-tolerated, with only 5 patients experiencing grade 3 toxicity, and no severe grade 4-5 toxicities reported, indicating that SABR boost can be a safe alternative when brachytherapy is not an option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy boost for cervical cancer when brachytherapy boost is not feasible. Lee, TH., Song, C., Kim, IA., et al.[2022]

Stereotactic ablative radiotherapy (SABR) for re-irradiation of recurrent pelvic cancer shows promise, with local control rates ranging from 51% to 100% in a review of 205 patients across 17 studies, although the studies were mostly small and retrospective.

The treatment appears to be well-tolerated, with only a few cases of severe toxicities (grade 3 and 4), suggesting that SABR could be a feasible option for patients with limited treatment choices, but more prospective studies are needed to establish a formal treatment pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pelvic re-irradiation using stereotactic ablative radiotherapy (SABR): A systematic review. Murray, LJ., Lilley, J., Hawkins, MA., et al.[2023]

Hypofractionated stereotactic body radiation therapy (SBRT) for early-stage nonsmall cell lung carcinoma was found to be safe and effective, with no significant toxicity reported in a study of nine patients over an 18-month follow-up period.

Using an active breath coordinator (ABC) during treatment resulted in smaller planning target volumes and less lung exposure to radiation compared to free breathing, suggesting that ABC may enhance treatment precision without increasing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for early-stage primary lung cancer, is an active breath coordinator necessary? An audit from a tertiary cancer care center. Madhavan, R., Renilmon, PS., Nair, HM., et al.[2018]

In a study of 67 patients with low-risk prostate cancer treated with stereotactic body radiotherapy (SBRT), significant late bladder and rectal toxicities were infrequent, with no grade 4 toxicities reported and only 3% experiencing grade 3 bladder toxicity.

The 4-year PSA relapse-free survival rate was 94%, indicating that SBRT is effective in controlling prostate cancer and should be considered as a treatment option alongside other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. King, CR., Brooks, JD., Gill, H., et al.[2022]

In a study assessing the effects of stereotactic ablative body radiotherapy (SABR) on a patient with a solitary kidney, renal function declined significantly, showing a 34% decrease at 3 months and stabilizing at a 43% loss by 12 months after receiving a single dose of 26 Gy.

The research indicates a clear dose-effect relationship, where the extent of kidney function loss correlates with the radiation dose delivered, highlighting the need for careful consideration of SABR's impact on healthy renal tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT. Jackson, P., Foroudi, F., Pham, D., et al.[2022]

In a study of 41 low-risk prostate cancer patients treated with hypofractionated stereotactic body radiotherapy (SBRT), the 5-year biochemical progression-free survival rate was an impressive 93%, indicating strong efficacy of this treatment.

The treatment was well-tolerated, with acute side effects resolving within 1-3 months and no severe (grade 4) toxicities reported, highlighting the safety of SBRT for localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes. Freeman, DE., King, CR.[2022]

Stereotactic body radiation therapy (SBRT) using a helical tomotherapy system was successfully used to treat a patient with locally advanced cervical cancer, showing no evidence of tumor recurrence after treatment.

The treatment was well-tolerated, with only mild side effects like grade 1 nausea and vomiting, and no severe toxicities or complications such as fistula formation, suggesting that SBRT could be a safe alternative to brachytherapy in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should helical tomotherapy replace brachytherapy for cervical cancer? Case report. Hsieh, CH., Wei, MC., Hsu, YP., et al.[2022]

In a phase I clinical trial involving patients with untreated locally advanced cervical cancer who were ineligible for intracavitary brachytherapy, the recommended stereotactic body radiotherapy (SBRT) boost dose was determined to be 22.5 Gy in three fractions, with no dose-limiting toxicities observed within 6 months after treatment.

All patients in the study achieved locoregional control, indicating that SBRT is a promising treatment option for this patient population, and further investigation in a phase II multi-center trial is planned.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining the recommended dose of stereotactic body radiotherapy boost in patients with cervical cancer who are unsuitable for intracavitary brachytherapy: a phase I dose-escalation study. Ito, K., Kito, S., Nakajima, Y., et al.[2020]

References

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

A Phase II Trial of Stereotactic Ablative Radiation Therapy as a Boost for Locally Advanced Cervical Cancer. [2020]

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

Stereotactic body radiation therapy via helical tomotherapy to replace brachytherapy for brachytherapy-unsuitable cervical cancer patients - a preliminary result. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Moving from standardized to personalized boxes and pears in radiation planning for cervical cancer. [2015]

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

Stereotactic ablative body radiotherapy boost for cervical cancer when brachytherapy boost is not feasible. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Pelvic re-irradiation using stereotactic ablative radiotherapy (SABR): A systematic review. [2023]

6. India pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for early-stage primary lung cancer, is an active breath coordinator necessary? An audit from a tertiary cancer care center. [2018]

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

Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT. [2022]

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

Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Should helical tomotherapy replace brachytherapy for cervical cancer? Case report. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Determining the recommended dose of stereotactic body radiotherapy boost in patients with cervical cancer who are unsuitable for intracavitary brachytherapy: a phase I dose-escalation study. [2020]