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

30 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 this with the trial coordinators or your doctor.

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

Research shows that neoadjuvant chemotherapy (NACT), which is a treatment given before the main treatment, can be effective for patients with locally advanced cervical cancer. Studies have found that platinum-based NACT can help shrink tumors before surgery, improving outcomes for some patients. ^{1 2 3 4 5}

Is the treatment safe for humans?

The safety of dose-dense cisplatin-based neoadjuvant chemotherapy (NACT) followed by surgery has been studied, and its toxicity profile (side effects) has been assessed in patients with locally advanced cervical cancer. ^{1 2 6 7 8}

How does biomarker testing with standard treatment differ from other treatments for cervical cancer?

This treatment is unique because it involves biomarker testing to better predict which patients will benefit from standard treatments like chemoradiotherapy (a combination of chemotherapy and radiation therapy). This approach aims to personalize treatment plans based on individual patient characteristics, potentially improving outcomes compared to traditional methods that do not use such predictive testing. ^{2 3 9 10 11}

What is the purpose of this trial?

This is a phase 0 clinical trial of molecular biomarkers in women with uterine cervix cancer. Women receive standard-of-care radiochemotherapy followed by brachytherapy. Blood samples are obtained to detect circulating levels of deoxyribonucleotides, human papillomavirus DNA, and circulating tumor cells.

Research Team

Denise Fabian, MD

Principal Investigator

University of Kentucky

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

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]

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]

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]

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]

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]

References

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

The Efficacy and Response Predictors of Platinum-Based Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Prognostic significance of p-STAT3 in patients with bulky cervical carcinoma undergoing neoadjuvant chemotherapy. [2012]

3. United States 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. [2022]

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

Body Weight Is a Valid Predictor of the Long-Term Prognosis of Cervical Cancer. [2022]

5. China pubmed.ncbi.nlm.nih.gov

Outcome evaluation of neoadjuvant chemotherapy in patients with stage IB2 or IIA cervical cancer: a retrospective comparative study. [2022]

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

CD44 isoform 6 (CD44v6) is a prognostic indicator of the response to neoadjuvant chemotherapy in cervical carcinoma. [2017]

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

Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Dose-Dense Neoadjuvant Chemotherapy plus Radical Surgery in Locally Advanced Cervical Cancer: A Phase II Study. [2015]

9. Japan pubmed.ncbi.nlm.nih.gov

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

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

Identification of a novel six-gene signature with potential prognostic and therapeutic value in cervical cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Predicting response to neoadjuvant chemotherapy in patients with cervical carcinoma: can we do without any longer? [2019]