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

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

NCT ID: NCT06262386

Condition: Lung Cancer
Relapse/Recurrence

Conditions: Official terms:
Recurrence
Cisplatin

Conditions: Keywords:
Circulating tumor cell
resectable non-small cell lung cancer
Early relapse

Study type: Interventional

Study phase: N/A

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Other

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Cisplatin based chemottherapy
Description: adjuvant therapy for high risk patient
Arm group label: Patient at risk for disease relapse after surgery

Summary: 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.

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.

Criteria for eligibility:
Criteria:
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

Gender: All

Minimum age: 20 Years

Maximum age: 90 Years

Healthy volunteers: No

Locations:

Facility:
Name: Ching-Yang Wu

Address:
City: Taoyuan City
Zip: 333
Country: Taiwan

Status: Recruiting

Contact:
Last name: Ching-Yang Wu

Phone: +886975368204
Email: wu.chingyang@gmail.com

Contact backup:
Last name: Jason CH Hsieh

Phone: +886975366137
Email: wisdom5000@gmail.com

Investigator:
Last name: Jui-Ying Fu
Email: Sub-Investigator

Investigator:
Last name: Ching-Feng Wu
Email: Sub-Investigator

Start date: August 1, 2023

Completion date: July 31, 2028

Lead sponsor:
Agency: Chang Gung Memorial Hospital
Agency class: Other

Collaborator:
Agency: National Science and Technology Council
Agency class: U.S. Fed

Source: Chang Gung Memorial Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06262386