Hypofractionated Radiotherapy for Cervical Cancer

Recruiting at 3 trial locations

Overseen By Lucas Mendez, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Must be taking: Cisplatin

Disqualifiers: FIGO stage IIIA, Previous radiotherapy, Inflammatory bowel disease, Connective tissue disorder, 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: Unknown

Duration: 6-8 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation therapy for cervical cancer to determine if it matches the effectiveness of the current standard treatment but with shorter sessions. It compares the usual treatment with a new schedule that delivers the same radiation dose in fewer visits. The researchers aim to assess the method's effectiveness and its side effects. Candidates may qualify if they have certain types of cervical cancer treatable with both chemotherapy (Concurrent Chemotherapy) and radiation, and have not received prior pelvic radiation. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial protocol 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?

Research has shown that combining high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) is generally well-tolerated by patients. One study found that using HDR brachytherapy in three sessions effectively treated advanced cervical cancer, with patients managing the treatment well. Another study demonstrated that combining HDR brachytherapy with EBRT improved tumor control and increased survival rates compared to other treatments.

Regarding safety, these treatments have produced good results with few serious side effects. Most patients did not experience severe negative reactions, indicating that the treatment is considered safe. Although this trial is in its early stages, previous studies support the treatment's safety, suggesting it is a promising option for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about hypofractionated radiotherapy for cervical cancer because it offers a potentially faster and more convenient treatment option. Unlike traditional radiotherapy, which involves smaller doses over many weeks, hypofractionated radiotherapy delivers higher doses in fewer sessions. This approach could reduce the overall treatment time and make it easier for patients to complete their therapy. Additionally, when combined with high-dose rate brachytherapy, it may enhance the effectiveness against cancer cells. This new protocol aims to maintain or even improve treatment outcomes while minimizing the burden on patients.

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

Research has shown that using both external beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy effectively treats advanced cervical cancer. Studies have found that this combination controls the tumor better than EBRT alone. One study found that patients receiving both treatments lived longer. In this trial, participants will be assigned to either an experimental arm with a shorter, more intense course of EBRT with HDR brachytherapy or a standard of care arm with the conventional approach. This suggests that the experimental approach might maintain or even enhance the benefits seen with the standard treatment. Overall, combining these therapies has become a standard treatment for this type of cancer because it effectively controls the disease. ^{1 5 6 7 8}

Who Is on the Research Team?

Lucas Mendez, MD

Principal Investigator

London Health Sciences Centre, Lawson Health Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with certain stages of cervical cancer (up to FIGO stage IIB) who haven't had previous pelvic/abdominal radiotherapy or require paraaortic nodal irradiation. They must be able to undergo an MR scan, have a performance status of 3 or less, and be candidates for chemotherapy with cisplatin.

Inclusion Criteria

My cervical cancer is at an early to mid-stage.

I am a candidate for brachytherapy.

My cervical cancer is limited to the cervix or has spread to nearby tissues.

Exclusion Criteria

Patient unable to undergo MR scan

My cancer is at a specific stage and has spread to certain lymph nodes.

I have had radiotherapy in my pelvic or abdominal area before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hypofractionated external-beam radiotherapy and weekly chemotherapy, followed by brachytherapy

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of acute and late toxicities

3 years and 3 months

Long-term follow-up

Participants are monitored for long-term outcomes such as progression-free survival, overall survival, and quality of life

8 years

What Are the Treatments Tested in This Trial?

Interventions

• Concurrent Chemotherapy
• External beam radiotherapy (EBRT) + High-dose rate (HDR) Brachytherapy Experimental
• External beam radiotherapy (EBRT) + High-dose rate (HDR) Brachytherapy Standard of Care

Trial Overview The HEROICC-Trial compares standard external beam radiotherapy plus chemotherapy followed by brachytherapy against a shortened (hypofractionated) radiotherapy regimen. The goal is to see if the experimental approach works well in Canada and how patients respond to it.

How Is the Trial Designed?

Group I: Arm 1 EBRT+High-dose (HDR) Brachytherapy Experimental Experimental Treatment 2 Interventions

Group II: Arm 2 EBRT+High-dose (HDR) Brachytherapy Standard of Care Active Control 2 Interventions

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

Approved in United States as Concurrent Chemotherapy for:

• Locally advanced cervical cancer

Approved in Canada as Concurrent Chemotherapy for:

• Locally advanced cervical cancer

Approved in European Union as Concurrent Chemotherapy for:

• Locally advanced cervical cancer

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Academic Medical Organization of Southwestern Ontario

Collaborator

Trials

17

Recruited

1,600+

Published Research Related to This Trial

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]

Volume-based high-dose-rate (HDR) brachytherapy (HDRVOL) plans significantly reduce radiation exposure to organs at risk (OAR) by 6-12% compared to traditional Point A (HDRPointA) plans, indicating a safer treatment approach for patients with locally advanced cervical cancer.

HDRVOL planning also improves the conformal index by 18-31%, demonstrating its efficacy in creating more precise radiation delivery to the target area while minimizing damage to surrounding healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric evaluation of Point A and volume-based high-dose-rate plans: a single institution study on adaptive brachytherapy planning for cervical cancer. Paul, AG., Nalichowski, A., Abrams, J., 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 77 patients with locally advanced cervical cancer, treatment with cisplatin, external beam radiotherapy, and two 9-Gy HDR brachytherapy insertions resulted in a 5-year progression-free survival rate of 75%, indicating effective disease control.

The treatment was associated with manageable side effects, with 47% of patients experiencing grade 3/4 gastrointestinal symptoms, but only 6% experiencing significant late toxicities, suggesting a favorable safety profile for this HDR brachytherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of concomitant cisplatin with external beam pelvic radiotherapy and two high-dose-rate brachytherapy insertions for the treatment of locally advanced cervical cancer. Novetsky, AP., Einstein, MH., Goldberg, GL., et al.[2022]

In a study of 113 patients with cervical cancer treated with high-dose-rate (HDR) brachytherapy at 9 Gy per fraction, the 5-year local control rate was 74.5%, indicating effective management of the disease.

The treatment demonstrated a low incidence of severe toxicity, with only 3.31% of patients experiencing Grade 3 or worse late toxicity, suggesting that this fractionation schedule is both safe and effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy in uterine cervical carcinoma. Patel, FD., Rai, B., Mallick, I., et al.[2019]

In a study of 95 patients with intermediate- or high-risk prostate cancer, a combined approach of high dose rate (HDR) brachytherapy and external beam radiotherapy (EBRT) was found to be well-tolerated, with manageable levels of toxicity reported by patients.

While urinary and bowel symptoms peaked shortly after treatment, most patients reported a return to baseline quality of life within 6 to 24 months, indicating that this treatment regimen effectively balances dose escalation with patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and health-related quality of life in prostate cancer treated with a single fraction of high dose rate brachytherapy combined with hypofractionated external beam radiotherapy. Choudhury, A., Arthur, C., Malik, J., et al.[2022]

In a study of 370 cervical cancer patients treated with either high dose rate (HDR) or low dose rate (LDR) brachytherapy, both methods showed similar pelvic control and survival rates, indicating that HDR is an effective treatment option.

The incidence of late complications was comparable between HDR (31.1%) and LDR (31.9%), with HDR showing a slightly lower rate of more severe complications (14% vs. 19%), suggesting that HDR brachytherapy is a safe alternative to LDR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results and complications of high dose rate and low dose rate brachytherapy in carcinoma of the cervix: Cerrahpaşa experience. Okkan, S., Atkovar, G., Sahinler, I., et al.[2019]

A treatment regimen of 45 Gy external beam radiotherapy combined with 24 Gy high-dose-rate brachytherapy is effective for patients with Stage II and III cervical cancer, achieving 5-year overall survival and local control rates of 53.7% and 62%, respectively.

Overall treatment time of up to 50 days was identified as a significant factor affecting survival and local control, suggesting that timely treatment is crucial for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy in the treatment of uterine cervix cancer. Analysis of dose effectiveness and late complications. Ferrigno, R., dos Santos Novaes, PE., Pellizzon, AC., et al.[2019]

Citations

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

The Impact of High-Dose-Rate Brachytherapy Radical concurrent chemoradiotherapy with combined external beam radiotherapy (EBRT) and brachytherapy is used to treat locally advanced cervical cancer.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24004730

Brachytherapy or external beam radiotherapy as a boost in ... This review analyzes the experience and trends in external beam radiotherapy for delivering a boost in locally advanced cervical cancer.

3. iaea.org iaea.org/newscenter/news/combining-external-radiation-with-high-dose-rate-brachytherapy-effective-for-cervical-cancer-iaea-study-confirms

Combining External Radiation with High-dose Rate ... The results showed significantly superior tumour control in the group that received external beam radiation therapy plus the(4 fractions X 7Gy) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8085872/

Contemporary external beam radiotherapy boost or high ... Survival outcomes were significantly different between patients with CC who received contemporary EBRT boost or HDR-BT boost.

5. cancerdiagnosisprognosis.org cancerdiagnosisprognosis.org/article/202/clinical-outcomes-and-toxicity-of-ct-guided-high-dose-rate-brachytherapy-in-women-with-locally-advanced-cervical-cancer

Clinical Outcomes and Toxicity of CT-guided High Dose ... Brachytherapy (BT) as a boost to external beam radiotherapy (EBRT) is the gold standard in the management of locally advanced cervical cancer ( ...

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

Cancer control and toxicity results of chemoradiation for ... Studies have consistently demonstrated the superiority of brachytherapy in improving local control and survival compared to other radiation ...

7. brachyjournal.com brachyjournal.com/article/S1538-4721(24)00453-7/fulltext

Clinical and dosimetric outcomes of a 3-fraction high-dose ... Three-fraction HDR brachytherapy boost was generally well-tolerated by patients and may be a viable alternative in the treatment of LACC.

8. cancerdiagnosisprognosis.org cancerdiagnosisprognosis.org/storage/cdp/3/2/cdp-3-194.pdf

Clinical Outcomes and Toxicity of CT-guided High Dose- ... Brachytherapy Task Group Report: A pooled analysis of clinical outcomes for high-dose-rate brachytherapy for cervical cancer. Brachytherapy 16(1): 22-43, 2017.