Study of Neoadjuvant Chemotherapy Versus Definite Concurrent Chemoradiotherapy for Locally Advanced Bulk Cervical Cancer

February 3, 2024 updated by: Chuangzhen Chen

Phase III Randomized Prospective Clinical Study of Neoadjuvant Chemotherapy With Gemcitabine and Cisplatin(GP) Versus Definite Cisplatin Combined Weekly Chemoradiotherapy for Locally Advanced Bulk Cervical Cancer

This phase III randomized prospective clinical study was conducted to compare the short-term and long-term outcomes of gemcitabine and cisplatin neoadjuvant chemotherapy versus definite cisplatin weekly concurrent chemoradiotherapy in patients with locally advanced bulk cervical cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Platinum-based concurrent chemoradiotherapy is the standard of care recommended by the NCCN for locally advanced cervical cancer of stage IB3, IIA2 and IIB-IVA (2018 FIGO stage) (cervical tumor ≥4cm). The 5-year survival rate of concurrent chemoradiotherapy for locally advanced cervical cancer has been reported in foreign literatures at 64.5-67%. The 3 - and 5-year survival rates of the concurrent chemoradiotherapy in our hospital were 78.6% and 70.5%, respectively, while the 3 - and 5-year survival rates of the concurrent chemoradiotherapy with cisplatin monotherapy were 66.4% and 63.1%, respectively. In the concurrent radiotherapy and chemotherapy, although many studies have tried paclitaxel, irinotecan, gemcitabine and other concurrent radiotherapy and chemotherapy with cisplatin, some encouraging results have been obtained, but at the same time, more obvious toxic and side effects have also appeared in the combination drug. At present, there is no evidence that the combined use of these radiotherapy sensitizers is superior to the single use of cisplatin. Adjuvant chemotherapy also did not show a survival advantage.

Neoadjuvant chemotherapy (NACT) is a systemic chemotherapy given before local treatment of malignant tumors (surgery or radiotherapy), mainly used for the treatment of breast cancer, cervical cancer, and solid head and neck tumors. Neoadjuvant chemotherapy plus surgery in locally advanced cervical cancer research more, but there is no specification of neoadjuvant chemotherapy plus radiation and chemotherapy research reports. Possible benefits of neoadjuvant chemotherapy: 1. Reduce tumor volume, reduce tumor displacement during radiation, and thus reduce the radiation dose to surrounding normal tissues (rectum, bladder, etc.); 2. Reduce the proportion of hypoxic cells and increase the radiotherapy sensitivity; 3. Suppression or elimination of micrometastatic lesions may exist in the whole body, and can prevent distant metastasis.

Rydzewska et al. conducted a large sample study showing that neoadjuvant chemotherapy can prolong overall survival and progression-free survival. For early and locally advanced cervical cancer, neoadjuvant chemotherapy combined with radical surgery is more meaningful than surgery alone. He et al. reported on 62 cases of Ⅰ b2 ~ Ⅱ b stage cervical cancer patients with paclitaxel plus cisplatin 2-3 courses of neoadjuvant chemotherapy, the total effective rate was 90.32%, among them the complete response rate was 30.65%, tumor after chemotherapy significantly smaller.

Gemcitabine (GEM) is a synthetic nucleoside derivative of cytosine, which mainly acts on S phase and has been used in solid tumors for more than 20 years. Duenas-Gonzalez et al. reported that gemcitabine combined with cisplatin induced chemotherapy in the primary treatment of locally advanced (IB2-IIIB) cervical cancer stage II study, the total response rate of induction chemotherapy plus surgery was 95% (7.5%CR and 87.5%PR), grade 3-4 granulocytopenia accounted for 13.8% and 3.4%, and non-hematological toxicity was slight. Therefore, the chemotherapy response rate of GP(gemcitabine/cisplatin) regimen was similar to that of PC (paclitaxel/cisplatin) regimen in cervical cancer, but the side effects were relatively small.

IMRT/VMAT modern precision radiotherapy technology is more and more popular in the radiotherapy of cervical cancer, precision radiotherapy has better conformal, can significantly reduce the external radiation dose of pelvis and small intestine; It is also possible to reduce the dose and volume of surrounding normal tissues (rectum, bladder, etc.) during target mapping and planning. However, the local tumor of the massive cervical cancer is huge, and the volume of the surrounding normal tissue decreases significantly during the radiotherapy and chemotherapy during irradiation, which results in increased displacement change of the surrounding normal tissue, so that the normal tissue outside the target area during the planning and design enters the irradiation field, and weakens the benefits of precise radiotherapy technology. Neoadjuvant chemotherapy reduces local cervical tumors in advance, improves tumor hypoxia and reduces tumor displacement during concurrent chemoradiotherapy. Theoretically, it has obvious benefits to reduce side effects in normal tissues around the week.

This study attempted to administer gemcitabine and cisplatin (GP) regimen neoadjuvant chemotherapy in large locally advanced cervical cancer, with the expectation that the neoadjuvant chemotherapy group could improve the local control rate, reduce the distant metastasis rate, and reduce the side effects of radiotherapy in normal tissues, thus improving the overall survival rate, and providing a scientific basis for the development of a rational, effective, low-toxicity, individualized comprehensive treatment plan suitable for modern precise radiotherapy technology for locally advanced cervical cancer.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
290

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Chuangzhen Chen, MD
  • Phone Number: 86-13923995569
  • Email: stccz@139.com

Study Contact Backup

  • Name: Yizhou Zhan, MD
  • Phone Number: 86-13929699280
  • Email: 6780540@qq.com

Study Locations

  • China
    • Guangdong
      • Shantou, Guangdong, China, 515031
        • Recruiting
        • Cancer Hospital, Shantou University Medical College
        • Contact:
          • Chuangzhen Chen, MD
          • Phone Number: 86-13923995569
          • Email: stccz@139.com
        • Principal Investigator:
          • Chuangzhen Chen, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologic proof of primary cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma.
  • According to the 2018 International Federation of Cervical Cancer Obstetrics and Gynecology (FIGO) staging standard, the patient was diagnosed with local tumor ≥4cm in stage IB3, IIA2, IIB-IVA by at least one expert with associate high degree or above in the department of gynecology and gynecology.
  • Age≥18 & ≤70.
  • ECOG score 0-2.
  • WBC ≥4.0×109/L, hemoglobin ≥60g/L, platelet ≥100.0×109/L; Serum bilirubin ≤ upper limit of normal, ALT, AST, ALP ≤ upper limit of normal ×2.5; Urea nitrogen (BUN) ≤ upper limit of normal ×1.5, creatinine (Cr)≤ upper limit of normal ×1.5.
  • Patients with prior malignancy are eligible if disease-free ≥ 5 years.
  • Signed study-specific informed consent form prior to study entry.

Exclusion Criteria:

  • Line has anti-tumor treatment, including chemotherapy, radiotherapy, surgery).
  • Stage Ia1- IB2 and IVB cervical cancer.
  • Patients with uncontrolled serious medical or mental illnesses.
  • Women in pregnancy or lactation.
  • Psychological, family, social factors, such as lead to no informed consent.
  • Into the group of the first five years in addition to the cervical cancer merger other patients with a history of malignant tumor.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Locally advanced bulk cervical cancer neoadjuvant chemotherapy group(NACT)

Radiation: Radiotherapy with IMRT/VMAT+192Ir-HDR brachytherapy Radiotherapy: 46Gy/23F to external pelvic radiotherapy and 14Gy/7F boost to imaging diagnosis of positive lymph nodes 192Ir-HDR brachytherapy:A Point dose 6Gy*4-6F

Drug: gemcitabine plus cisplatin,cisplatin Neoadjuvant chemotherapy:gemcitabine and cisplatin (GP) regimen*2 cycles Concurrent Chemotherapy: Weekly cisplatin chemotherapy ≥5 cycles
Drug: gemcitabine and cisplatin
Neoadjuvant chemotherapy:gemcitabine and cisplatin
Active Comparator: Locally advanced bulk cervical cancer chemoradiotherapy group(CCRT)

Radiation: Radiotherapy with IMRT/VMAT+192Ir-HDR brachytherapy Radiotherapy: 46Gy/23F to external pelvic radiotherapy and 14Gy/7F boost to imaging diagnosis of positive lymph nodes 192Ir-HDR brachytherapy:APoint A dose 6Gy*4-6F

Drug: cisplatin Concurrent Chemotherapy: Weekly cisplatin chemotherapy ≥5 cycles
Drug: gemcitabine and cisplatin
Neoadjuvant chemotherapy:gemcitabine and cisplatin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Overall survival
Time Frame: 2 years
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Local-regional control
Time Frame: 2 years
2 years
Distant metastasis-free survival
Time Frame: 2 years
2 years
Disease-free survival
Time Frame: 2 years after randomization
2 years after randomization
Acute and late toxicities using CTCAE v4.0
Time Frame: 2 years
The probabilities of grade ≥ 3 acute toxicities and 2-year late toxicities of bladder and rectum.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chuangzhen Chen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Chuangzhen Chen, MD, Cancer Hospital, Shantou University Medical College

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 27, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 27, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 12, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 6, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 3, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NACT-CC-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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