Accelerated Brachytherapy + Chemo Radiation for Cervical Cancer

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating locally advanced cervical cancer by combining chemotherapy (cytotoxic therapy) with a special type of radiation therapy. The trial aims to determine if starting with two doses of focused radiation treatment, known as brachytherapy (internal radiation therapy), before the usual radiation and chemotherapy, can improve outcomes such as reducing cancer recurrence and side effects on the digestive and urinary systems. It seeks patients newly diagnosed with certain types of cervical cancer who have not received prior pelvic radiation. Those diagnosed with cervical cancer and without previous radiation therapy may find this trial suitable. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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?

Studies have shown that accelerated brachytherapy, when combined with chemotherapy and radiation, can effectively treat cervical cancer. The safety of this approach is crucial. Research indicates that high-dose-rate brachytherapy, especially when guided by images, is generally well-tolerated by patients. Some studies found that this method can be completed in a shorter time, potentially reducing side effects associated with longer treatments.

For the shortened version of external beam radiation, past studies reported that serious side effects were rare. In one study, only 2.5% of patients experienced severe side effects, suggesting the treatment is usually safe for patients.

Regarding chemotherapy, research shows it works well with other treatments like radiation. Chemotherapy combinations, especially those based on cisplatin, are common and have been thoroughly tested. However, like any treatment, it can have side effects, which the healthcare team often manages.

Overall, researchers are studying the combination of these treatments to ensure safety and effectiveness. It's important to discuss any concerns with healthcare providers and understand the potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for cervical cancer, which typically involve a longer course of radiation and chemotherapy, this new protocol combines accelerated brachytherapy with hypofractionated external beam radiation and chemotherapy. This means the radiation dose is delivered more intensely over a shorter period, potentially reducing the total treatment time to just 36-42 days. Researchers are excited about this approach because it starts with brachytherapy, a highly targeted radiation method, right from the beginning, which may improve tumor control and outcomes. By integrating these advanced techniques earlier in the treatment process, there is hope for better efficacy and fewer side effects.

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

This trial will evaluate the combination of accelerated brachytherapy with chemo radiation therapy for cervical cancer. Studies have shown that combining external beam radiation and brachytherapy can reduce the recurrence of cervical cancer and extend patient survival. Image-guided brachytherapy, particularly when used early, is linked to better outcomes. A shorter course of external beam radiation therapy, known as hypofractionated therapy, reduces treatment time and may also improve survival rates. Adding chemotherapy to these treatments has increased survival compared to supportive care alone, with some studies showing survival rates improving by up to 8%. Together, these treatments aim to enhance the efficiency and effectiveness of therapy for cervical cancer patients. ^{1 3 5 6 7}

Who Is on the Research Team?

Jessika Contreras, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7276688/

The Impact of High-Dose-Rate Brachytherapy Discussion. Cervical cancer is highly curable with early stage disease, and the published literature demonstrates combining EBRT with brachytherapy can result ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24005954

Image-guided brachytherapy in cervical cancer including ... Multiple studies have demonstrated a decrease in local recurrence and an improvement in overall survival when brachytherapy is used in these patients.2, 3, 4 ...

3. obstetricgynecoljournal.com obstetricgynecoljournal.com/articles/cjog-aid1195.php

A Update on Brachytherapy for Cervical Cancer: A Review Outcomes of high-dose-rate interstitial brachytherapy in the treatment of locally advanced cervical cancer: long-term results. Int J Radiat ...

4. brachyjournal.com brachyjournal.com/article/S1538-4721(24)00441-0/fulltext

lessons from the COVID pandemic for high dose-rate ... To evaluate outcomes of cervical cancer patients treated with abbreviated high dose rate brachytherapy (HDR-BT) that used 2-implants and delivered 4–5 ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1442712/full

Brachytherapy for cervical cancer: from intracavitary to ... In this paper, the research progress of three-dimensional (3D) brachytherapy for cervical cancer in recent years is reviewed.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1538472125002855

Cancer control and toxicity results of chemoradiation for ... This study assessed cancer control and toxicity following an accelerated 3-fraction brachytherapy protocol.

7. international-journal-of-gynecological-cancer.com international-journal-of-gynecological-cancer.com/article/S1048-891X(24)00595-4/fulltext

Image-guided brachytherapy in cervical cancer including ... This review gives an overview of the major milestones that occurred in the development of image-guided adaptive brachytherapy in the last two decades, including ...