Combined Relapse Prediction Model for Resectable Non-Small Cell Patients - a Prospective Clinical Feasibility Trial

February 7, 2024 updated by: Chang Gung Memorial Hospital

Utilizing Perioperative Variation Trends of Circulating Tumor Cells and Tumor Pathological Characteristics as a Combined Relapse Prediction Model for Resectable Non-Small Cell Patients - a Prospective Clinical Feasibility Trial

For patients with lung cancer who have undergone tumor resection, early relapse significantly impacts survival. However, there are currently no reliable screening or imaging tools available to identify patients at risk of early relapse. To address this clinical challenge, many studies have focused on understanding the clinicopathologic characteristics associated with an increased risk of early relapse. Despite these efforts, we can identify patients at risk but cannot pinpoint which individuals will actually experience early relapse. Studies on adjuvant therapy have shown improved survival in cases of more advanced disease but have not demonstrated a reduction in early relapse rates.

In our preliminary analysis of previous study data, we observed that patients with a smaller reduction in circulating tumor cells (CTCs) within the first three days after surgery, followed by an increase on the third-day post-operation, are more likely to experience early relapse during regular monitoring. This pattern may be indicative of minimal residual disease. By combining trends in circulating tumor cell variations with pathologic characteristics, we aim to select patients for adjuvant therapy who are at high risk of developing early relapse.

The objective of our study is to employ screening based on circulating tumor cell dynamics and pathologic features to identify patients likely to experience early relapse and to assess the effectiveness of adjuvant therapy in these cases.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

For patients with resectable lung cancer, anatomic resection alongside mediastinal lymph node dissection is pivotal in removing all tumor tissue visible on imaging from the patient's body. Despite these efforts, early relapse remains a significant issue. Literature review shows that the early relapse rate varies between 8 to 10%, potentially due to undetectable occult metastasis by imaging modalities, suggesting the presence of minimal residual disease or tumor cells evading the primary site. Limitations in imaging, such as the slice thickness in computed tomography (CT) scans, which range from 0.375 to 0.5 centimeters, can render tumors smaller than the slice thickness invisible. Similarly, tumors smaller than 0.5 cm may not accumulate sufficient F18-Deoxyglucose to be detectable in positron emission tomography (PET) scans. Additionally, tumor cells may migrate to extrapulmonary sites via lymphatic drainage or circulation.

Survival studies have predominantly focused on the pathologic TNM stage, which aggregates different disease presentations with similar survival outcomes. However, the heterogeneity inherent in pathology may help in identifying patients prone to relapse. From a tumor biology perspective, tumor cells may detach from surrounding tissues, becoming more invasive and entering the bloodstream. Circulating tumor cells (CTCs) have been recognized early in cancer stages and are correlated with treatment response, tumor genetic alterations, and survival. Research has combined CT tumor size and CTCs in a malignancy prediction model for suspicious pulmonary lesions, highlighting that CTCs can rebound in patients experiencing early relapse, indicating occult metastases or minimal residual disease.

Systemic adjuvant therapy is considered the best approach to minimize disease relapse in resectable lung cancer patients. Although many studies have sought to identify patients at risk of relapse to improve survival, the presence of intrapulmonary (N1) or mediastinal (N2) lymph node invasion significantly affects survival in non-small cell lung cancer patients. Even tumors smaller than 1 cm carry a risk of lymph node metastases, with respective risks for cT1a, cT1b, and cT1c tumors reported as 3.8%, 16.3%, and 19.6%. Therefore, patients with tumors larger than 1 cm are recommended adjuvant therapy due to the high risk of lymph node involvement. Adjuvant chemotherapy is advised for patients with stages 1b to 3a, showing a 5.4% survival benefit by the fifth postoperative year, although this benefit diminishes in subsequent years. This could be due to adjuvant therapy being administered based on the pathologic stage rather than the likelihood of relapse. Tumor heterogeneity might also influence the response to different therapeutic regimens. Molecular profiling of tumors has identified mutations predicting responses to targeted therapies and elucidated drug resistance mechanisms, offering more precise treatments and improving survival. Targeted and immune therapies have shown improved survival in specific tumor subgroups.

This study aims to utilize trends in CTC variations as a screening tool to identify patients at risk of relapse and prescribe adjuvant therapy to evaluate the therapeutic efficacy and survival impact of CTCs.

Study Type

Interventional

Enrollment (Estimated)

358

Phase

  • Not Applicable

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 Backup

Study Locations

  • Taiwan
      • Taoyuan City, Taiwan, 333
        • Recruiting
        • Ching-Yang Wu
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Jui-Ying Fu
        • Sub-Investigator:
          • Ching-Feng Wu

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients who presented with resectable disease ( Clinical stage 1a to 3a)
  2. Patients who received tumor resection

Exclusion Criteria:

  1. Pathologic stage greater than stage 3b or 4
  2. Pathologic stage less than stage 1a1
  3. Could not complete treatment course
  4. Could not receive blood sampling for CTC (circulating tumor cell) or regular surveillance

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: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patient at risk for disease relapse after surgery

  1. we utilized a relapse prediction model that combined perioperative variation trends of circulating tumor cells and pathologic characteristics that were collated with relapse

    1. circulating tumor cell variation trend: difference between the CTC count on post-operation day 3 and day 1; difference between the CTC count on post-operation day 3 and post-operation
    2. pathologic staging 0-1a/ 1b-4

  2. patient with high relapse for relapse

    • Adjuvant was recommended as NCCN guidelines recommended
Drug: Cisplatin based chemottherapy
adjuvant therapy for high risk patient

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Accuracy of proposed relapse prediction model
Time Frame: follow up in 3 month-interval
  1. Utilized the enrolled patients to testify proposed relapse prediction model
  2. Calculated Positive prediction rate, Negative prediction rate, accuracy
  3. Goal: high positive prediction rate, lower negative prediction rate, high accuracy
follow up in 3 month-interval
early relapse rate
Time Frame: follow up in 3 month-interval

  1. adjuvant therapy based on proposed relapse prediction model

    • calculate the early relapse rate (relapse within 3 years)

  2. utilized historical cohort as historical control (cohort that utilized to establish proposed relapse prediction model

    • adjuvant therapy based on TNM stage
    • calculate the early relapse rate (relapse within 3 years)
    • follow up Chest CT/ CTC in 3-month interval
follow up in 3 month-interval

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall surveival
Time Frame: follow up in 3 month-interval

Goal: difference of overall survival among patients with relapse risk

  1. treatment based on proposed relapse prediction model
  2. calculate the overall survival

  3. utilized historical cohort as historical control ( cohort that utilized to establish proposed relapse prediction model

    • treatment based on TNM stage
    • calculate the overall survival rate
follow up in 3 month-interval

Collaborators and Investigators

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

Sponsor

Chang Gung Memorial Hospital

Collaborators

National Science and Technology Council

Investigators

  • Principal Investigator: Ching-Yang Wu, Chang Gung Memorial Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

August 1, 2023

Primary Completion (Estimated)

July 31, 2028

Study Completion (Estimated)

July 31, 2028

Study Registration Dates

First Submitted

September 22, 2023

First Submitted That Met QC Criteria

February 7, 2024

First Posted (Actual)

February 16, 2024

Study Record Updates

Last Update Posted (Actual)

February 16, 2024

Last Update Submitted That Met QC Criteria

February 7, 2024

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202202172B0

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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