Accelerated Brachytherapy + Chemo Radiation for Cervical Cancer

Overseen By Jessika A Contreras, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Washington University School of Medicine

Disqualifiers: Prior pelvic radiotherapy, other malignancy, metastatic disease, hysterectomy, others

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The standard treatment for locally advanced cervical cancer is well established as a combination of chemotherapy and radiation, typically over 25-28 daily fractions with the addition of a brachytherapy boost to the primary tumor. An important component to treatment efficacy is overall treatment time. Prolongation of overall treatment time has been shown to lead to worse local control and overall survival; thus, strategies to effectively deliver radiation efficiently is required. This is a pragmatic feasibility study to determine the impact of upfront brachytherapy combined with hypofractionated external beam radiation for patients with locally advanced cervical cancer (FIGO 2018 stage IB3-IVA) on late gastrointestinal and genitourinary toxicity, oncologic outcomes including recurrence free survival, and systemic and local immune response.

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 Accelerated Brachytherapy + Chemo Radiation for Cervical Cancer?

Research shows that using high-dose-rate brachytherapy (a type of internal radiation) with external beam radiation therapy and chemotherapy is effective for treating advanced cervical cancer, improving survival rates and patient outcomes. ^{1 2 3 4 5}

Is accelerated brachytherapy with chemo radiation generally safe for humans?

Research shows that high-dose-rate brachytherapy combined with external beam radiation and chemotherapy is commonly used for treating cervical cancer, and studies have focused on patient outcomes and toxicities. This suggests that the treatment has been evaluated for safety, although specific safety data details are not provided in the abstracts. ^{1 3 6 7 8}

How is the Accelerated Brachytherapy + Chemo Radiation treatment for cervical cancer different from other treatments?

This treatment combines high-dose-rate brachytherapy (a type of internal radiation) with chemotherapy and hypofractionated external beam radiation (a method that delivers larger doses of radiation over fewer sessions), which may improve local control and survival rates compared to traditional low-dose-rate brachytherapy and standard radiation schedules. ^{1 2 3 8 9}

Research Team

Jessika Contreras, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for individuals with locally advanced cervical cancer (stages IB3-IVA). Participants must be eligible to receive chemotherapy and radiation. Specific details about inclusion and exclusion criteria are not provided, but typically these would outline health requirements and any factors that could interfere with treatment or skew results.

Inclusion Criteria

My oncologist has approved me for targeted radiation therapy.

I have been newly diagnosed with stage IB3 to IVA cervical cancer.

My cervical cancer is one of three types: squamous, adenocarcinoma, or adenosquamous.

Exclusion Criteria

I have had radiation therapy to my pelvic area before.

I have had cancer in my reproductive or pelvic area before.

Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test day of or within 7 days prior to simulation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Brachytherapy

Participants receive 2 fractions of brachytherapy prior to initiation of EBRT-based chemoradiotherapy

1 week

Chemoradiotherapy

Participants receive hypofractionated external beam radiation therapy (EBRT) with concurrent chemotherapy

5-6 weeks

Follow-up

Participants are monitored for late gastrointestinal and genitourinary toxicity, oncologic outcomes, and immune response

2 years and 6 weeks

Treatment Details

Interventions

• Chemotherapy
• Hypofractionated external beam radiation
• Image-guided brachytherapy

Trial Overview The study tests a new approach called ABC-RT which combines upfront brachytherapy (a type of internal radiation) with hypofractionated external beam radiation, alongside standard chemotherapy. The goal is to see if this method can improve outcomes while reducing treatment time.

Participant Groups

Group I: Accelerated Brachytherapy Forward Chemo Radiation Therapy Experimental Treatment 3 Interventions

Accelerated Brachytherapy Forward Chemo Radiation Therapy (ABC-RT) combines hypofractionated external beam radiation therapy (EBRT) with concurrent chemotherapy and early upfront, image-guided brachytherapy. In this study, patients start with 2 fractions of brachytherapy prior to initiation of EBRT-based chemoradiotherapy. Total time from treatment planning is approximately 36-42 days.

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The transition to high-dose-rate (HDR) intracavitary brachytherapy (ICBT) in conjunction with external beam radiotherapy for treating locally advanced cervical cancer resulted in acceptable long-term outcomes, with a 5-year progression-free survival rate of 63.7% and overall survival rate of 69.3%.

Nodal involvement was identified as a significant prognostic factor affecting survival, indicating that patients with lymph node involvement may require more aggressive treatment strategies to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of High-Dose-Rate Brachytherapy: Measuring Clinical Outcomes in the Primary Treatment of Cervical Cancer. Song, J., Alyamani, N., Bhattacharya, G., et al.[2022]

In a study of 210 cervical cancer patients, continuous radiation therapy (CRT) showed a progression-free survival (PFS) rate of 71%, compared to 56% for sequential radiation therapy (SRT), although this difference was not statistically significant.

SRT was associated with a higher incidence of late rectal injuries (13% vs. 25%) due to the higher doses per fraction of HDR-BT, suggesting that the 8 Gy per fraction in SRT may be too high and indicating a need for optimization in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary radiotherapy of stage IIA/B-IIIB cervical carcinoma. A comparison of continuous versus sequential regimens. Mayer, A., Nemeskéri, C., Petneházi, C., et al.[2006]

In a study of 12,721 cervical cancer patients in Korea, the utilization rate of brachytherapy after external beam radiation therapy decreased from 84% in 2005 to 78% in 2013, with significant regional variations.

Brachytherapy, when added to curative external beam radiation therapy, was found to be independently associated with improved cancer-specific survival and overall survival, highlighting its importance in treatment for cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brachytherapy utilization rate and effect on survival in cervical cancer patients in Korea. Kim, YA., Yang, MS., Park, M., et al.[2021]

Out of 550 patients with cervical cancer treated with external beam radiotherapy and high-dose-rate intracavitary radiotherapy, 214 completed the treatment, showing a 5-year disease-free survival rate of 58% for stage I, but only 15% for stage IV, indicating poorer outcomes in advanced stages.

The study suggests that treatment outcomes could be improved for advanced-stage patients by increasing the total radiation dose, shortening treatment duration, and incorporating chemotherapy for those with localized disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical radiotherapy treatment (EBRT + HDR-ICRT) of carcinoma of the uterine cervix: outcome in patients treated at a rural center in India. Jain, VS., Singh, KK., Shrivastava, R., et al.[2019]

In a study of 113 patients with localized cervical cancer in Sri Lanka, the 2-year disease-free survival (DFS) rate was found to be 63.7%, indicating a moderate level of effectiveness for the combined treatment of external-beam radiotherapy (EBRT) and intracavitary brachytherapy.

Delays in receiving intracavitary brachytherapy after EBRT were significantly associated with worse DFS, highlighting the need for improved access to brachytherapy resources to enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical External-Beam Radiotherapy in Combination With Intracavitary Brachytherapy for Localized Carcinoma of the Cervix in Sri Lanka: Is Treatment Delayed Treatment Denied? Joseph, N., Jayalath, H., Balawardena, J., et al.[2021]

In a study of 32 cervical cancer patients treated with 6 fractions of brachytherapy after external beam radiotherapy, the treatment resulted in a high response rate, with 84% showing no residual disease six weeks post-treatment.

The five-year overall survival rate was 75%, and the treatment was associated with very low rates of severe toxicities, indicating that this brachytherapy regimen is both effective and safe for advanced cervical cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of 6 fractions of 5.3 Gray HDR brachytherapy in combination with external beam radiotherapy for treatment of cervical cancer. Koh, WY., Lim, K., Tey, J., et al.[2018]

In a study of 105 cervical cancer patients treated with high-dose-rate (HDR) brachytherapy and external beam radiotherapy, the overall three-year survival rate was 72%, with local control achieved in 80% of patients, indicating the efficacy of this treatment approach.

The treatment was associated with a low complication rate, with only 3.4% of patients experiencing grade III complications, suggesting that HDR brachytherapy is a safe option for cervical cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multifractionated high-dose-rate brachytherapy with concomitant daily teletherapy for cervical cancer. Han, I., Malviya, V., Chuba, P., et al.[2019]

In a study of 80 cervical cancer patients, those treated with external beam chemoradiation followed by radical hysterectomy had similar survival rates to those receiving chemoradiation followed by brachytherapy, suggesting that surgery can be a viable alternative when brachytherapy is unavailable.

While both treatment groups experienced different types of complications, the overall survival and progression-free survival rates were comparable, indicating that radical hysterectomy does not compromise patient outcomes after chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brachytherapy versus radical hysterectomy after external beam chemoradiation: a non-randomized matched comparison in IB2-IIB cervical cancer patients. Cetina, L., Garcia-Arias, A., Candelaria, M., et al.[2022]

Brachytherapy significantly improves local control and survival rates in cervical cancer patients, especially when performed promptly after external irradiation to keep treatment under 53 days.

While low dose-rate brachytherapy has shown improved outcomes and fewer complications, the role of interstitial brachytherapy remains uncertain, and further research is needed to clarify the benefits and risks of combining brachytherapy with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Curietherapy in uterine cervix cancers: what therapeutic trends?]. Haie-Meder, C., Breton, C., de Crevoisier, R., et al.[2019]

References

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

The Impact of High-Dose-Rate Brachytherapy: Measuring Clinical Outcomes in the Primary Treatment of Cervical Cancer. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Primary radiotherapy of stage IIA/B-IIIB cervical carcinoma. A comparison of continuous versus sequential regimens. [2006]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Brachytherapy utilization rate and effect on survival in cervical cancer patients in Korea. [2021]

4. India pubmed.ncbi.nlm.nih.gov

Radical radiotherapy treatment (EBRT + HDR-ICRT) of carcinoma of the uterine cervix: outcome in patients treated at a rural center in India. [2019]

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

Radical External-Beam Radiotherapy in Combination With Intracavitary Brachytherapy for Localized Carcinoma of the Cervix in Sri Lanka: Is Treatment Delayed Treatment Denied? [2021]

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

Outcome of 6 fractions of 5.3 Gray HDR brachytherapy in combination with external beam radiotherapy for treatment of cervical cancer. [2018]

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

Multifractionated high-dose-rate brachytherapy with concomitant daily teletherapy for cervical cancer. [2019]

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

Brachytherapy versus radical hysterectomy after external beam chemoradiation: a non-randomized matched comparison in IB2-IIB cervical cancer patients. [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Curietherapy in uterine cervix cancers: what therapeutic trends?]. [2019]