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

Trial Summary

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 data supports the effectiveness of the treatment Brachytherapy, Internal Radiation Therapy, Radioactive Seed Implantation, Cisplatin, Platinol, Cisplatinum, platamin, neoplatin, cismaplat, cis-diamminedichloroplatinum(II), CDDP, Intensity Modulated Radiation Therapy (IMRT) for cervical cancer?

Research shows that combining cisplatin (a chemotherapy drug) with radiation therapy is effective for treating locally advanced cervical cancer, improving survival rates and reducing recurrence. Additionally, intensity-modulated radiation therapy (IMRT) is used to target cancer more precisely, potentially reducing side effects. ^{1 2 3 4 5}

Is radiochemotherapy for cervical cancer safe for humans?

Research shows that combining radiotherapy with cisplatin (a chemotherapy drug) is generally safe for treating cervical cancer, though some patients may experience side effects like leukopenia (a decrease in white blood cells). ^{2 3 6 7 8}

How is the radiochemotherapy treatment for cervical cancer unique?

This treatment combines cisplatin (a chemotherapy drug) with Intensity Modulated Radiation Therapy (IMRT), which allows for precise targeting of the cancer while minimizing damage to surrounding healthy tissue. The use of cisplatin in different dosing schedules (weekly or triweekly) alongside radiation is a standard approach, but the combination with IMRT may offer improved precision and potentially fewer side effects. ^{2 4 9 10 11}

What is the purpose of this trial?

The goal of this clinical trial is to investigate the use of hypofractionated radiation (delivery of fewer but larger doses of radiation) with concurrent chemotherapy for women with metastatic of bulky uterine cervix cancer. The main questions it aims to answer are: * What is the MRI-assessed rate of response at 1-month and 3-months post-treatment? * What is the safety and tolerability of cisplatin-based hypofractionated pelvic Intensity Modulated Radiation Therapy (IMRT) followed by brachytherapy? * What is the median progression-free survival and overall survival at 1 and 2 years for patients who undergo cisplatin-based hypofractionated pelvic IMRT? * What is the proportion of patients who complete the treatment in prescribed timeframe? * What the levels of cervix cancer circulating tumor cells pretherapy and after treatment? To confirm eligibility, within four weeks prior to study enrollment, all patients will undergo the following: * Complete history and physical exam, GOG performance status evaluation * Standard of care scans, which include staging CTs and/or PET scans, and MRI to verify eligibility and appropriate stage of disease. Blood tests will be done to check various organ functions. Treatment will be administered on an outpatient basis. The main difference between the proposed regimen in the trial and standard of care is as follows: 1. The trial has a shortened course of EBRT. Standard of care utilizes 25 treatments, also known as "fractions" of EBRT, while the trial utilizes 8 fractions of EBRT. An equivalent "biological effective dose" is achieved by increasing the radiation dose per fraction. 2. The concurrent cisplatin dosing is shortened from 5-6 cycles of cisplatin to 2 cycles of cisplatin. The dose of cisplatin is 40 mg/m2. This protocol requires photon IMRT technique followed by high dose rate (HDR) brachytherapy. The therapies use focused energy beams to kill cancer cells. Radiation therapy must be completed within 30 days +/- 2 days of initiation. Computed tomography simulation with the patient in a head-first laying on back-supine position is required. MRI-guided treatment planning and image guidance during treatment for motion management will be used. IMRT will be given once daily Monday-Thursday, four fractions per week. The high-dose-rate (HDR) brachytherapy following institutional protocol. Brachytherapy will be delivered twice per week with a 2-day break in between sessions. A total of four brachytherapy treatments will be delivered. After active therapy is completed, treatment-related toxicity will be assessed at the 1-month post-treatment completion visit and again at the 3-month post-treatment completion. Patients removed from the study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event(s). Routine MRI imaging to assess treatment response to radiotherapy is conducted at Day 15. Treatment response to radiotherapy followed by brachytherapy will be assessed at the 1- month and 3-months post-treatment completion. Following the 3-months post-treatment completion, study participants will be followed for disease progression and survival status until Year 2 post-treatment initiation. NOTE: Cervical cancer patients are routinely followed (clinical surveillance) every 3-months during the first two years post-treatment.

Research Team

Denise Fabian, MD

Principal Investigator

University of Kentucky

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Survival and toxicity differences between 5-day and weekly cisplatin in patients with locally advanced cervical cancer. [2016]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Concurrent weekly single cisplatin vs triweekly cisplatin alone with radiotherapy for treatment of locally advanced cervical cancer: a meta-analysis. [2020]

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

Definitive extended field intensity-modulated radiotherapy and concurrent cisplatin chemosensitization in the treatment of IB2-IIIB cervical cancer. [2021]

4. Switzerland 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. [2015]

5. United States 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. [2016]

6. United States 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. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Dose escalated intensity modulated radiotherapy in the treatment of cervical cancer. [2018]

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

A phase I study of adjuvant intensity-modulated radiotherapy with concurrent paclitaxel and cisplatin for cervical cancer patients with high risk factors. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Randomized phase 3 trial comparing 2 cisplatin dose schedules in 326 patients with locally advanced squamous cell cervical carcinoma: long-term follow-up. [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

Concomitant radiochemotherapy of cervical cancer: is it justified to reduce the dosage of cisplatin? [2021]