Single-drug Chemotherapy Plus Immunotherapy in Metastatic Non-small Cell Lung Cancer Elderly Patients

Prospective, Single-arm Phase II Clinical Study of Single-drug Chemotherapy Plus Immunotherapy in Metastatic Non-small Cell Lung Cancer Elderly Patients

Lung cancer is the cancer with the highest morbidity and mortality among men in the world. The proportion of elderly lung cancer patients in the global lung cancer population is steadily increasing, at the same time, it is also the age group with the highest lung cancer mortality, but there is little evidence for treatment of elderly lung cancer patients. In this study, the investigators set the definition of the elderly to 65 years and older.

The progression-free survival (PFS) and overall survival (OS) of immunotherapy plus chemotherapy were higher than those of chemotherapy alone, which established the dominant position of dual-drug chemotherapy combined with immunotherapy. Studies showed that elderly patients benefit from immunotherapy.

It is controversial whether elderly advanced non-small-cell-lung-cancer (NSCLC) patients should receive single-drug chemotherapy or dual-drug chemotherapy. MILES-3 and MILES-4 studies show that in the advanced NSCLC elderly patients, combined with cisplatin on the basis of single drug chemotherapy can not significantly prolong OS, and can not improve the overall health status of patients. Based on the results of this study, single drug chemotherapy is still the preferred first-line regimen. Another study showed that carboplatin combined with paclitaxel had longer OS than gemcitabine or vinorelbine alone in elderly patients with advanced NSCLC with a performance status (PS) score of less than 2. In the era of immunotherapy, it is not clear whether single-drug chemotherapy combined with immunotherapy can achieve the same therapeutic effect as dual-drug chemotherapy combined with immunotherapy. Therefore, the purpose of this study is to investigate the efficacy and safety of single-drug chemotherapy plus immunotherapy in elderly metastatic NSCLC patients.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Lung Cancer; Elderly Patients
• Intervention / Treatment: Drug: Single drug chemotherapy plus immunotherapy

Detailed Description

Lung cancer is the cancer with the highest morbidity and mortality among men in the world. The age range in which lung cancer is most commonly diagnosed is 65-74 years old. The proportion of elderly lung cancer patients in the global lung cancer population is steadily increasing, at the same time, it is also the age group with the highest lung cancer mortality, but there is little evidence for treatment of elderly lung cancer patients. The investigators pay special attention to elderly patients because they are a unique group.

With regard to the definition of "elderly", considering that more than half of cancer patients are aged 65 or above. Therefore, we set the definition of the elderly in this phase II clinical study to 65 years and older.

The results of Keynote-042 study, Keynote-189 study and Keynote-407 study all showed that the progression-free survival (PFS) and overall survival (OS) of immunotherapy plus chemotherapy were higher than those of chemotherapy alone, which established the dominant position of dual-drug chemotherapy combined with immunotherapy. Meta analysis showed that in patients with advanced NSCLC, immunotherapy prolonged OS and PFS compared with chemotherapy, and the prolongation of PFS was not related to age, while OS also benefited in patients aged 65 to 75 years. To sum up, elderly patients benefit from immunotherapy.

It is controversial whether elderly advanced NSCLC patients should receive single-drug chemotherapy or dual-drug chemotherapy. MILES-3 and MILES-4 studies show that in the advanced NSCLC elderly patients, combined with cisplatin on the basis of single drug chemotherapy can not significantly prolong OS, and can not improve the overall health status of patients. Based on the results of this study, single drug chemotherapy is still the preferred first-line regimen. Another study showed that carboplatin combined with paclitaxel had longer OS than gemcitabine or vinorelbine alone in elderly patients with advanced NSCLC with a PS score of less than 2. In the era of immunotherapy, it is not clear whether single-drug chemotherapy combined with immunotherapy can achieve the same therapeutic effect as dual-drug chemotherapy combined with immunotherapy. Therefore, the purpose of this study is to investigate the efficacy and safety of single-drug chemotherapy plus immunotherapy in elderly metastatic NSCLC patients, in order to reduce the adverse reactions without reducing the curative effect and improve their quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 49
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Guang Han; Phone Number: 13886048178; Email: hg7913@hotmail.com
• Study Contact Backup: Name: Lulu Shi; Phone Number: 027-87670318

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Recruiting
      • Hubei Cancer Hospital
      • Contact: Han Guang, MD
      • Principal Investigator: Han Guang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Regardless of sex, age ≥ 65, PS 0-2.
2. metastatic NSCLC of American Joint Committee on Cancer (AJCC) 8th edition confirmed by histology or cytology.

3. No mutation or fusion of common driving genes, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS-1).

   (adenocarcinoma requires genetic testing).

4. Positive expression of Programmed cell death 1 ligand 1（PD-L1） (TPS ≥ 1%).
5. First-line treatment (stable brain or bone metastasis, or stable symptoms after local treatment).
6. Before treatment, there were perfect enhanced CT images of chest and supraclavicular area, and measurable tumor lesions.
7. The estimated survival time is not less than 6 months.
8. The clinical laboratory criteria within 2 weeks before treatment are as follows: hemoglobin ≥ 110g / L, leukocytes ≥ 4x109 / L, platelet ≥ 100x109 / L, liver and kidney function indexes (such as glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, urea nitrogen, creatinine) were all within 1.25 times of the upper limit of the normal value.
9. Informed understanding and voluntary participation in this study, and informed consent has been signed.

Exclusion Criteria:

1. Mutation or fusion of common driving genes (EGFR,ALK or ROS1).
2. Have received systemic treatment before.
3. Previous suffering from other malignant tumors (except stage I non-melanotic skin cancer or cervical carcinoma in situ) or other malignant tumors at the same time.
4. Other drugs are being tested.
5. Patients with positive HIV and are receiving antiviral therapy .
6. Active pulmonary tuberculosis.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Metastatic NSCLC patients over 65 years old; In metastatic NSCLC patients over 65 years old, we employed gemcitabine or paclitaxel or vinorelbine plus immunotherapy for squamous cell carcinoma. Paclitaxel or pemetrexed plus immunotherapy are available for non-squamous and non-small cell lung cancer.

Drug: Single drug chemotherapy plus immunotherapy; The choice of chemotherapy plus immunotherapy for squamous cell carcinoma is gemcitabine or paclitaxel or vinorelbine. Paclitaxel or pemetrexed are available for monotherapy for non-squamous and non-small cell lung cancer. Immunotherapy drugs can be Pembrolizumab /Penpulimab/ Camrelizumab/ Tislelizumab / Sintilimab/ sulgarizumab and so on; Other Names: monochemotherapy plus immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival	up to 12 months
Objective response rate	up to 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	up to 18 months
Disease control rate	up to 6 months

Collaborators and Investigators

• Sponsor: Hubei Cancer Hospital
• Investigators: Principal Investigator: Guang Han, Hubei Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: August 22, 2023
• First Submitted That Met QC Criteria: September 1, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunomodulating Agents
• Other Study ID Numbers: Unicorn

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No