Biomarker Testing with Standard Treatment for Cervical Cancer

Overseen By Yvonne Taul

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Denise Fabian

Disqualifiers: Active malignancy, Prior malignancy, Prior pelvic radiotherapy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of using blood samples to identify biomarkers that might help doctors better understand and treat cervical cancer. Participants will receive standard cancer treatments, including a combination of radiation and cisplatin chemotherapy, followed by brachytherapy (a type of internal radiation). The goal is to determine if certain molecules in the blood can reveal how the cancer behaves or responds to treatment. Women with confirmed cervical cancer that cannot be treated with surgery alone and who have not received prior pelvic radiation are suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cervical cancer care.

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.

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

Research has shown that combining radiotherapy with cisplatin chemotherapy is generally well-tolerated by patients with cervical cancer. Studies have found that this treatment can cause some side effects, but they are often manageable. Common side effects include nausea, tiredness, and mild skin reactions. Although long-term information on side effects is limited, most patients do not experience serious problems. This combination treatment is widely used and continues to undergo study for its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how biomarker testing can be paired with the standard treatment for cervical cancer, which typically includes radiotherapy and chemotherapy. Unlike traditional approaches that apply a one-size-fits-all treatment, this method aims to personalize therapy based on a patient’s unique biomarkers. This could lead to more effective treatments by targeting the specific characteristics of an individual's cancer, potentially improving outcomes and reducing side effects. By customizing treatment plans, the hope is to maximize the effectiveness of the standard radiochemotherapy and brachytherapy regimen.

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

Research has shown that combining chemotherapy (drugs that kill cancer cells) with radiotherapy (high-energy rays that kill cancer cells) is more effective for treating advanced cervical cancer than radiotherapy alone. Specifically, cisplatin, when used with radiotherapy, helps patients live longer and prevents the cancer from worsening. One study found that a higher dose of cisplatin improved survival rates in patients with more advanced cervical cancer. These findings support this treatment combination, which participants in this trial will receive, as a strong option for improving outcomes in women with advanced 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 untreated cervical cancer stages IB3 (>4cm), II, III, or IVA. It's not suitable for those who've had other invasive cancers in the last three years (except certain skin cancers and in situ cervical carcinoma) or prior pelvic radiotherapy that could harm normal tissue.

Inclusion Criteria

My cervical cancer is at a stage that cannot be cured by surgery alone.

Exclusion Criteria

I haven't had cancer in the last 3 years, except for skin cancer or cervical pre-cancer.

I have another active cancer besides the one being treated.

I have had pelvic radiotherapy that might affect my treatment now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiochemotherapy

Participants receive standard daily radiotherapy plus weekly cisplatin

6-8 weeks

Brachytherapy

Participants undergo brachytherapy following radiochemotherapy

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• NA

Trial Overview The study tests molecular biomarkers in women undergoing standard radiochemotherapy followed by brachytherapy for uterine cervix cancer. Researchers will analyze blood samples to detect specific DNA and tumor cells.

How Is the Trial Designed?

Group I: Radiochemotherapy followed by brachytherapy Experimental Treatment 1 Intervention

Standard daily radiotherapy plus weekly cisplatin followed by brachytherapy

Who Is Running the Clinical Trial?

Denise Fabian

Lead Sponsor

Trials

2

Recruited

50+

Charles Kunos

Lead Sponsor

Trials

2

Recruited

30+

UK Radiopharma Alliance

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study of 219 patients with locally advanced cervical cancer, platinum-based neoadjuvant chemotherapy (NACT) showed an overall response rate of 58.9%, with 8.7% achieving complete remission, indicating its efficacy in treating this condition.

Patients who responded to NACT had significantly better overall survival and progression-free survival rates, and those with earlier stage cancer and smaller tumors were more likely to respond positively to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Response Predictors of Platinum-Based Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer. Huang, Y., Liu, L., Cai, J., et al.[2022]

In a study analyzing 607 cervical cancer patients, several clinical factors such as aneuploidy score, histologic grade, and body weight were identified as significant predictors for disease-free survival (DFS) and overall survival (OS), highlighting their potential use in prognosis assessment.

For patients admitted to the hospital, age over 60, advanced TNM stage, and higher body weight were found to significantly influence long-term outcomes, suggesting that these factors should be considered in treatment planning and patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body Weight Is a Valid Predictor of the Long-Term Prognosis of Cervical Cancer. Lu, L., Ji, S., Jiang, J., et al.[2022]

In a study of 22 patients with locally advanced cervical cancer, dose-dense cisplatin-based neoadjuvant chemotherapy resulted in a 52.6% overall response rate, with 26.3% achieving a complete response and 26.3% a partial response.

While the treatment was generally well-tolerated, 18% of patients experienced significant hematological toxicity, and there were serious adverse events, including one case each of ototoxicity, transient ischemic attack, and myocardial infarction, indicating a need for further research to enhance safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Dense Neoadjuvant Chemotherapy plus Radical Surgery in Locally Advanced Cervical Cancer: A Phase II Study. Benedetti Panici, P., Palaia, I., Marchetti, C., et al.[2015]

In a study of 1997 women aged 35-45 in China, those with moderate to high HPV loads had significantly higher cumulative incidence rates of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), indicating that HPV load is a strong predictor of cervical cancer risk.

The findings suggest that a moderate or high HPV load could serve as an effective triage indicator for HPV-positive women, potentially streamlining cervical cancer screening and management, as it showed similar efficacy to cytologic findings in identifying women at risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Human Papillomavirus DNA Load in Predicting the Long-term Risk of Cervical Cancer: A 15-Year Prospective Cohort Study in China. Zhao, X., Zhao, S., Hu, S., et al.[2022]

In a study of 363 patients with stage IB2 or IIA cervical cancer, those who received neoadjuvant chemotherapy (NACT) showed a lower survival rate within the first year compared to those who did not receive NACT, although this difference was not present at the 3-year follow-up.

NACT did not provide significant benefits in reducing mortality or clinical deterioration over time, suggesting that it may not be advantageous for patients undergoing surgical resection and postoperative chemoradiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome evaluation of neoadjuvant chemotherapy in patients with stage IB2 or IIA cervical cancer: a retrospective comparative study. Yan, W., Qiu, S., Si, L., et al.[2022]

A novel six-gene prognostic signature (APOC1, GLTP, ISG20, SPP1, SLC24A3, and UPP1) was identified that effectively predicts overall survival in cervical cancer patients and is associated with the immune response and tumor microenvironment.

This six-gene signature may also indicate the effectiveness of immune checkpoint inhibitors (ICIs) in treatment, with three of the genes (UPP1, ISG20, and GLTP) showing potential as new drug targets for cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a novel six-gene signature with potential prognostic and therapeutic value in cervical cancer. Qu, X., Shi, Z., Guo, J., et al.[2022]

In a study of 55 patients with stage IIB cervical cancer undergoing neoadjuvant chemotherapy (NACT), the clinical response rate was 80%, indicating that this treatment can be effective for many patients.

However, the study found that none of the evaluated clinico-pathologic variables could predict which patients would respond to NACT, suggesting that only women with primarily resectable tumors should be considered for this treatment to avoid potential harm from nonresponse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting response to neoadjuvant chemotherapy in patients with cervical carcinoma: can we do without any longer? De Jonge, ET., Lindeque, BG., Burger, W., et al.[2019]

In a study of 21 women with stage Ib and IIa bulky cervical carcinomas treated with neoadjuvant chemotherapy (NAC), CD44v6 expression was identified as a significant predictor of response to treatment, suggesting that lower levels of CD44v6 before NAC may indicate a better chance of responding to the therapy.

Despite some patients responding to NAC, the study found that the response did not correlate with improved disease outcomes, highlighting the complexity of treatment efficacy and the need for further research into other factors influencing survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD44 isoform 6 (CD44v6) is a prognostic indicator of the response to neoadjuvant chemotherapy in cervical carcinoma. Costa, S., Terzano, P., Bovicelli, A., et al.[2017]

In a study of 29 patients with bulky cervical carcinoma undergoing neoadjuvant chemotherapy, 69% were found to be p-STAT3-positive, which was associated with longer disease-free survival rates (P = 0.03).

Patients with p-STAT3 positivity had a higher likelihood of clinical nodal involvement (P = 0.046), suggesting that while p-STAT3 can indicate a favorable prognosis, it may also correlate with more advanced disease features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of p-STAT3 in patients with bulky cervical carcinoma undergoing neoadjuvant chemotherapy. Choi, CH., Song, SY., Kang, H., et al.[2012]

High levels of Lumican (LUM) mRNA in cervical squamous cell carcinoma (CESC) patients are associated with poor response to concurrent chemoradiotherapy (CCRT), indicating it could serve as a novel biomarker for predicting treatment efficacy.

LUM overexpression may contribute to CCRT resistance by altering the immune microenvironment, with potential mechanisms involving the PARs and IL1 signaling pathways, as revealed by gene expression analyses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma. Hu, G., Xiao, Y., Ma, C., et al.[2023]

Neoadjuvant chemotherapy (NAC) before surgery may improve survival for cervical cancer patients with stage Ib2, while concurrent chemoradiotherapy (CCRT) has shown a significant survival benefit in advanced stages (III/IVA) with a 28%-50% reduction in death risk based on five large randomized clinical trials.

A meta-analysis of 19 RCTs involving 4580 patients indicated that CCRT significantly improves overall survival and progression-free survival, leading to its recommendation as the standard therapy for advanced cervical cancer in the U.S., although further research is needed to optimize treatment protocols for different patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy for uterine cancer: current status and perspectives. Kuzuya, K.[2012]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4538167/

Efficacy of concurrent single-agent chemotherapy using ... Concurrent chemoradiotherapy has proven to be more effective on patients with advanced cervical cancer than radiotherapy alone. Although cisplatin has been ...

2. ejgo.org ejgo.org/pdf/10.3802/jgo.2025.36.e10

Efficacy and safety of cisplatin combined with paclitaxel ... Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10547408/

Ten years survival results of randomized study comparing ... The current standard of treatment for locally advanced cervical cancer is concurrent chemo-radiation with improved overall survival (OS) by 6% with manageable ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24035540

Efficacy of cumulative cisplatin dose on survival in patients ... Our study indicated that a cumulative cisplatin dose of ≥200mg improved overall survival in patients with FIGO stage III cervical cancer. Advanced age, poorer ...

5. nejm.org nejm.org/doi/full/10.1056/NEJM199904153401502

Concurrent Cisplatin-Based Radiotherapy and ... Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11790991/

Efficacy and safety of cisplatin combined with paclitaxel ... This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) ...

7. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)01438-7/fulltext

an international, multicentre, randomised phase 3 trial In conclusion, this short-course induction chemotherapy regimen followed within 7 days by chemoradiotherapy improves survival of patients with ...

8. nrgoncology.org nrgoncology.org/Home/News/Post/nrg-oncology-trial-supports-radiotherapy-alone-following-radical-hysterectomy-should-remain-the-standard-of-care-for-early-stage-intermediate-risk-cervical-cancer

News Post Template The outcomes of this trial help confirm that cisplatin chemotherapy given adjuvantly with radiotherapy is not a superior alternative. Future ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38745137/

Efficacy and safety of different chemotherapy regimens ... The two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0305737203001178

Acute and long-term toxicity following radiotherapy alone ... This paragraph summarises the scarce available data on long-term toxicity for the combined radiotherapy and chemotherapy treatment for cervical cancer (Table 5) ...