Radiochemotherapy for Cervical Cancer

Overseen By Denise Fabian, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Denise Fabian

Must be taking: Cisplatin

Must not be taking: Investigational agents

Disqualifiers: Concurrent malignancy, Prior pelvic radiotherapy, Cardiac disease, 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: 19

20 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 cervical cancer by combining radiation and chemotherapy. The goal is to evaluate how effectively this treatment shrinks tumors and to assess its safety. It involves fewer radiation sessions with higher doses, alongside a reduced number of chemotherapy cycles. The chemotherapy uses Cisplatin, a common drug. Women with large or locally advanced cervical cancer, who do not require urgent systemic therapy, may be suitable candidates. The trial will measure patient responses and monitor their health for up to two years. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 your specific situation with the trial coordinators or your doctor.

What prior data suggests that this protocol is safe for treating cervical cancer?

Past studies have shown that the chemotherapy drug cisplatin can cause side effects. Patients with advanced cervical cancer who received it weekly experienced immediate issues like nausea and low blood counts. However, it remains generally safe with close monitoring.

Research on Intensity Modulated Radiation Therapy (IMRT) indicates it is well-tolerated. Studies have found it causes fewer side effects compared to other radiation methods, as it targets tumors more precisely and protects healthy tissue.

Brachytherapy, another type of radiation, involves placing radioactive material inside the body to directly target cancer. Studies show it is effective and safe when guidelines are followed.

While both cisplatin and radiation treatments can have side effects, they are commonly used and have proven safety records in treating cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for cervical cancer?

Researchers are excited about this treatment combination for cervical cancer because it integrates advanced techniques to potentially enhance effectiveness. Unlike traditional radiation therapy, Intensity Modulated Radiation Therapy (IMRT) precisely targets tumors while sparing healthy tissue, reducing side effects. The treatment also includes high-dose rate brachytherapy, delivering radiation directly to the tumor, maximizing impact. Additionally, the use of weekly Cisplatin infusions aims to enhance the effectiveness of radiation, potentially improving outcomes compared to conventional methods. This innovative approach is promising for providing more targeted and effective treatment for cervical cancer patients.

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

In this trial, participants will receive a combination of treatments: Cisplatin, Intensity Modulated Radiation Therapy (IMRT), and Brachytherapy. Research has shown that cisplatin can extend the lives of cervical cancer patients, particularly those in advanced stages. Studies have found that doses exceeding 200 mg of cisplatin significantly improve survival chances. IMRT reduces side effects and enhances survival rates. Additionally, brachytherapy, which targets radiation directly at the tumor, has proven very effective in controlling cancer, with high survival rates one and two years post-treatment. Together, these treatments offer a promising approach to managing cervical cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Denise Fabian, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for women with metastatic or bulky uterine cervix cancer. Participants must have a complete physical exam, performance status evaluation, and standard scans to confirm eligibility. They should be able to receive outpatient treatment and follow the study's schedule.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My organs and bone marrow are working well.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

My heart function is classified as class 2B or better according to the NYHA.

Currently receiving any other investigational agent(s) for the treatment of cancer

History of allergic reactions attributed to compounds of similar chemical or biologic composition to Cisplatin or other agents used in study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Radiation and Chemotherapy

Participants receive hypofractionated radiation therapy with concurrent cisplatin chemotherapy

4 weeks

8 visits (in-person)

Brachytherapy

High dose rate brachytherapy is administered twice per week with a 2-day break in between sessions

2 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 1-month and 3-months post-treatment

3 months

3 visits (in-person)

Long-term Follow-up

Participants are followed for disease progression and survival status until Year 2 post-treatment initiation

up to 2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Brachytherapy
• Cisplatin
• Intensity Modulated Radiation Therapy (IMRT)

Trial Overview

The trial tests hypofractionated radiation therapy combined with fewer cycles of chemotherapy (cisplatin) compared to standard care. It uses IMRT followed by HDR brachytherapy, aiming to see how well patients respond via MRI, safety, tolerability, and survival rates after treatment.

How Is the Trial Designed?

Group I: Cisplatin with concurrent Intensity Modulated Radiotherapy and Brachytherapy Experimental Treatment 3 Interventions

Cisplatin two (2) one-time weekly intravenous infusions at 40 mg/m2 (70mg maximum) IMRT once daily, four fractions per week for 2 weeks 4.56 Gy x 8 fractions High dose rate Brachytherapy twice per week with a 2-day break in between sessions for a total of four brachytherapy treatments. The dose is 7 Gy x 4 fractions

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Denise Fabian

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

In a phase I trial involving 20 patients with cervical cancer, the maximum safe dose of WR2721 was determined to be 825 mg/m2/d when given alongside cisplatin and radiation therapy.

The main side effect observed was hypotension, which led to dose adjustments, while other significant toxicities included transient azotemia and leukopenia, but no serious long-term complications were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot trial of cisplatin, radiation, and WR2721 in carcinoma of the uterine cervix: a New York Gynecologic Oncology Group study. Wadler, S., Beitler, JJ., Rubin, JS., et al.[2017]

The maximum-tolerated dose (MTD) of paclitaxel when combined with cisplatin and pelvic radiotherapy for cervical cancer patients was determined to be 50 mg/m2 per week, with diarrhea identified as the main dose-limiting toxicity.

In a study of 18 patients, the combination treatment resulted in a high overall response rate of 92.3%, with 7 complete and 5 partial responses, indicating that this regimen could be an effective option for treating locally advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. Pignata, S., Frezza, P., Tramontana, S., et al.[2020]

In a phase II study involving 27 patients with locally advanced or recurrent cervical carcinoma, the combination of cisplatin and Taxol chemotherapy with radiotherapy resulted in a complete clinical response in all patients, indicating high efficacy of this treatment approach.

The treatment was generally well tolerated, although some patients experienced significant side effects such as grade 3-4 neutropenia and grade 3 anemia, suggesting that while effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial with cisplatin-paclitaxel cytotoxic treatment and concurrent external and endocavitary radiation therapy in locally advanced or recurrent cervical cancer. Miglietta, L., Franzone, P., Centurioni, MG., et al.[2015]

In a multicenter phase II trial involving 68 patients with locally advanced cervical cancer, concurrent chemoradiotherapy (CCRT) using weekly cisplatin and paclitaxel resulted in a high complete response rate of 76.5%.

The treatment demonstrated favorable long-term outcomes, with 2-year progression-free survival at 83.8% and overall survival at 92.7%, while maintaining manageable safety profiles with a 25% rate of late complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of concurrent chemoradiotherapy with weekly cisplatin and paclitaxel in patients with locally advanced uterine cervical cancer: The JACCRO GY-01 trial. Umayahara, K., Takekuma, M., Hirashima, Y., et al.[2016]

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