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

Trial Summary

What is the purpose of this trial?

External radiation given in 25 fractions or so together with weekly chemotherapy and followed by 3 or 4 fractions of brachytherapy is the standard of care for patients with locally advanced cervical cancer. This study investigates the role of shortened external radiotherapy regimen (hypofractionated radiotherapy) by randomizing patients to this experimental regimen versus the standard of care.The purpose of this study is to access the feasibility of patient accrual to this trial in the Canadian setting and to provide an initial evaluation of cancer response and treatment tolerability.

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.

What data supports the effectiveness of this treatment for cervical cancer?

Research shows that using external beam radiotherapy (EBRT) combined with high-dose-rate (HDR) brachytherapy is effective in treating locally advanced cervical cancer. Studies have reported positive outcomes and survival rates when these treatments are used together, especially when combined with chemotherapy like cisplatin. ^{1 2 3 4 5}

Is hypofractionated radiotherapy for cervical cancer safe?

Studies show that combining high-dose-rate brachytherapy with external beam radiotherapy for cervical cancer is generally safe, though it can have side effects. These treatments have been used effectively with manageable toxicity levels in patients. ^{3 4 5 6 7}

What makes hypofractionated radiotherapy for cervical cancer unique?

This treatment combines high-dose-rate (HDR) brachytherapy, which delivers radiation directly to the tumor, with external beam radiotherapy (EBRT) and chemotherapy, offering a more targeted and potentially more effective approach compared to traditional low-dose-rate (LDR) brachytherapy. ^{1 2 3 8 9}

Research Team

Lucas Mendez, MD

Principal Investigator

London Health Sciences Centre, Lawson Health Research Institute

Eligibility Criteria

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

I am 18 years old or older.

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

I am a candidate for brachytherapy.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. 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]

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

High-dose-rate brachytherapy in the treatment of uterine cervix cancer. Analysis of dose effectiveness and late complications. [2019]

5. United States 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. [2022]

6. England 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. [2022]

7. Poland 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. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Results and complications of high dose rate and low dose rate brachytherapy in carcinoma of the cervix: Cerrahpaşa experience. [2019]

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

High-dose-rate brachytherapy in uterine cervical carcinoma. [2019]