Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Hypoglycemic Agents

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Metformin

Gefitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Gefitinib and metformin. Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning TKI therapy, if possible, but TKI therapy will not be delayed for metformin loading.

Gefitinib and placebo. Placebo was given to patients in the same way as that of metformin in Arm A.

Gefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.

Gefitinib and Metformin

Gefitinib and placebo

Yong He, MD

The purpose of this study is to determine whether metformin in combination with gefitinib are effective in patients with previously untreated advanced or metastatic Non-Small-Cell Lung cancer with epidermal growth factor receptor (EGFR) mutations

Primary Objectives: To determine the 1 year progression-free survival (PFS) of the combination of metformin and gefitinib in patients who harbors EGFR-mutant with previously untreated advanced or metastatic pulmonary adenocarcinoma.

Secondary Objectives:

A. To evaluate the response to therapy and overall survival of the combination of metformin with gefitinib in patients who harbors EGFR-mutant with previously untreated advanced or metastatic pulmonary adenocarcinoma.

B. To acquire preliminary data regarding the effects of metformin on interleukin-6 (IL-6) levels in tumor and serum.

Treatment will be administered on an outpatient basis. Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning gefitinib, if possible, but gefitinib administration will not be delayed for metformin loading.

Gefitinib will be administered 250mg QD continuously. Metformin will be administered continuously, beginning one week before beginning gefitinib, if possible, but tyrosine kinase inhibitors (TKI) will not be delayed for metformin loading.

Maintenance Therapy Patients responding to this therapy will be maintained with metformin (1000 mg twice daily) and gefitinib.

Duration of Therapy

In the absence of treatment delays due to adverse events, treatment may continue until one of the following criteria applies:

1. Disease progression,
2. Intercurrent illness that prevents further administration of treatment,
3. Unacceptable adverse events(s),
4. Patient decides to withdraw from the study, or
5. General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.

Combination of Metformin With Gefitinib to Treat NSCLC

A Phase II, Randomized, Placebo Controlled Study to Evaluate the Efficacy of the Combination of Gefitinib and Metformin in Patients With Locally Advanced and Metastatic Non-Small-Cell-Lung-Cancer

IL-6 level in tumors and blood serum of patients.

One year progression-free survival (PFS) of the patients.

The response to therapy and overall survival of the patients.

Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Director of Department of Respiratory Diseases

Blood and Lymph Conditions

Thrombocytopenia

Blood Platelet Disorders

Hematologic Diseases

Cytopenia

Gemcitabine

Carboplatin

Cisplatin

Antimetabolites

Participants received a placebo subcutaneous injection on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice.

Participants received romiplostim 250 μg administered subcutaneously on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice.

Participants received romiplostim 500 μg administered subcutaneously on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice.

Participants received romiplostim 750 μg administered subcutaneously on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice.

Romiplostim is a thrombopoiesis recombinant protein that targets the thrombopoietin (TPO) receptor which results in increased platelet production.

Romiplostim

Placebo

The purpose of this study is to identify an effective, well tolerated dose and schedule of romiplostim that is appropriate for the treatment of chemotherapy induced thrombocytopenia (CIT) in patients with non-small cell lung cancer receiving gemcitabine and platinum.

Dose/ Schedule Finding Trial of Romiplostim for Chemotherapy-Induced Thrombocytopenia (CIT) in Non-Small Cell Lung Cancer (NSCLC)

Phase 2, Randomized, Double Blind, Placebo-Controlled Dose and Schedule Finding Trial to Evaluate the Safety and Efficacy of AMG 531 For Treatment of Chemotherapy-Induced Thrombocytopenia in Subjects With Advanced Non-Small Cell Lung Cancer Already Receiving Gemcitabine and Platinum.

This summary includes all treatment-emergent adverse events recorded from the start of investigational product on this study, or any worsening of adverse events initially experienced before initiation of this study.

The duration of grade 3 or 4 thrombocytopenia (defined as platelet count \<50 x 10\^9/L) experienced during the first on study chemotherapy cycle by treatment group.

The number of participants in each treatment group with grade 3 or 4 thrombocytopenia during the first on study treatment cycle. Per the Common Terminology Criteria for Adverse Events (CTCAE) v3.0, participants with a platelet count \< 50 x 10\^9/L, but ≥ 25 x 10\^9/L are considered to have Grade 3 thrombocytopenia and participants with a platelet count \< 25 x 10\^9/L are considered to have Grade 4 thrombocytopenia. Additionally, participants with a platelet transfusion during the first on-study treatment cycle were classified as having Grade 3/4 thrombocytopenia.

Number of participants who were administered platelet transfusions during first on study treatment cycle.

Platelet count on Day 22 of the first on study chemotherapy treatment cycle (planned Day 1 of next cycle) by treatment group

Number of participants who required a gemcitabine dose reduction on Day 8 of the first on study chemotherapy cycle.

Amgen

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Romiplostim 250 µg

Romiplostim 500 µg

Romiplostim 750 µg

Total

Age Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Race/Ethnicity, Customized

Study Director

Safety Analysis Set, composed of all randomized participants who received at least one dose of study medication.

Number of Participants With Adverse Events

Efficacy Analysis Set, composed of all randomized participants except those who were replaced (participants who discontinued prior to the completion of at least 1 romiplostim treatment cycle for non-platelet-related reasons).

Duration of Grade 3 or 4 Thrombocytopenia

Efficacy Analysis Set, composed of all randomized participants except those who were replaced.

Number of Participants Experiencing Grade 3 or 4 Thrombocytopenia During the First Treatment Cycle.

Number of Participants With Platelet Transfusions

Efficacy Analysis Set, composed of all randomized participants except those who were replaced

Platelet Count on Day 22

Gemcitabine Dose Reduction on Day 8 of the First Chemotherapy Cycle

Overall Study

Antipyretics

Anti-Inflammatory Agents

Antirheumatic Agents

Fibrinolytic Agents

Analgesics

Platelet Aggregation Inhibitors

Aspirin

Trametinib

Dabrafenib

Primary IIIB-IV BRAF V600E mutated advanced non-small cell lung cancer in a population of patients with advanced lung cancer proposed to be treated with Trametinib， Dabrafenib and Asprin

Treatment drug: Dabrafenib 150 mg BID, Trametinib 2 mg QD, Aspirin 100 mg/tablet, 1 tablet/time, QD

Combind asprin with Trametinib and Dabrafenib

He Yong, MD

The purpose of this study is to observe the safety and efficacy of Aspirin combined with Trametinib and Dalafenib in the treatment of advanced BRAF V600E mutated non-small cell lung cancer (NSCLC)

lung cancer is the leading cause of morbidity and mortality in China, and non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. The incidence of V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in NSCLC is 1.5% to 3.5%, and BRAF V600 accounts for about 30-50% of all BRAF mutations, among them, V600E mutation is the most common . NSCLC patients with BRAF V600 mutation have poor prognosis and shorter overall survival (OS). In terms of drug therapy for these patients didn't get a better clinical benefits of chemotherapy and immunotherapy, and the progression free survival (PFS) of chemotherapy is only 1.5\~4.2 months . The PFS of patients with BRAF-mutated NSCLC treated with immune checkpoint inhibitors was only 3.1 to 5.3 months . In recent years, the application of targeted therapy has brought new hope for patients with lung cancer BRAF mutation. In three cohorts of the Phase II clinical trial BRF113928, the BRAF inhibitor darafenib, was demonstrated has a significant efficacy as a single agent in treated patients with BRAF V600E mutation (cohort A), combined with mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor trametinib in treated patients (cohort B), and combined with trametinib in treated patients (cohort C), respectively. Objective response rates (ORR) were 33.0%, 63.2%, and 64.0%, and PFS were 5.5, 9.7, and 14.6 months, respectively. BRF113928 research shows that Dabrafenib combined with Trametinib had good efficacy in the treatment of BRAFV600 mutant NSCLC patients, regardless of whether it was used as first-line therapy or back-line therapy, and was superior to BRAF single-agent targeted therapy. In terms of safety, the most common adverse event (AE) of Dabrafenib combined with Trametinib was fever. In cohort B and cohort C, the incidence of fever of all grades was 46% and 64%, respectively, but most of them were grade , while the incidence of grade 3-4 AE was relatively low, 2% and 11%. In general, it is safe and controllable . The main management methods for fever AE caused by Dabrafenib combined with Trametinib as follows: after the first occurrence of fever syndrome, the patient should stop taking both drugs and immediately start oral antipyretic therapy. After the fever, it is still recommended to continue the drug for 3 days before stopping the fever treatment. The selection and usage of related antipyretic drugs should be comprehensively evaluated by doctors, and the options include non-steroidal anti-inflammatory drugs, acetaminophen, and anethene. At present, the latest NCCN and CSCO both regard Dabrafenib combined with Trametinib as the preferred first-line treatment for BRAF V600E mutated advanced NSCLC patients . In March 2023, Dabrafenib combined with Trametinib entered the national medical insurance directory, reducing the economic burden of patients. However, drug resistance to targeted drugs is inevitable. Studies have shown that the resistance mechanism of BRAF/MEK inhibitors is mainly mediated by the PI3K-Akt-mtor and RAS-RAF-MEK pathways, such as cell cycle related gene changes, PI3K-AKT pathway activation, NRAS/KRAS mutations, etc. Drug resistance mechanism of Dabrafenib combined with Trametinib is complicated, there are few opportunities to use targeted drugs, also lack of clear recommendation for follow-up treatment guidelines, usually systemic treatment such as immunotherapy and chemotherapy are adopted. How to overcome the resistance mechanism, delay drug resistance, and further prolong the PFS and OS of patients of Dabrafenib combined with Trametinib still need more exploration.

Previous epidemiological studies have suggested that aspirin may reduce the incidence of certain cancers, including lung cancer. A study from the United States included 365 patients with advanced non-small cell lung cancer treated with Osimertinib, 77 of whom were taking aspirin while taking Osimertinib. The results showed that the median PFS of patients treated with aspirin was 21.3 months, which was significantly longer than the median PFS of 11.6 months of patients treated with Osimertinib alone. However, the median OS of patients treated with aspirin was lower than that of patients treated with Osimertinib alone, which was 32.3 months. Combined with aspirin could significantly reduce the risk of death of patients by 44%, suggesting that EGFR-TKI combined with aspirin could improve the patients' PFS and reduce the risk of death and bleeding events. And the same as the targeted drugs, Dabrafenib who joint Trametinib whether can combine with aspirin? How safe is it? Can the combination of aspirin with Dabrafenib and Trametinib improve the PFS and OS of patients? Aspirin has antipyretic and analgesic effects, while one of the most common adverse reactions of Dabrafenib combined with Trametinib is fever. Can the combination of Dabrafenib combined with Trametinib reduce the occurrence of adverse events of fever? At present, in the field of lung cancer, there is no literature report on aspirin combined with Dabrafenib and Trametinib in the treatment of BRAF V600E mutated advanced NSCLC. In order to solve the above problem, further improve the BRAF V600E mutations in NSCLC patients with long-term survival, we proposed the observational phase II study to evaluate the efficacy and safety of aspirin combined with Dabrafenib and Trametinib in advanced NSCLC with BRAF V600E mutation.

Primary Objectives: To determine the progression-free survival time (PFS) of aspirin combined with Dabrafenib and Trametinib;

Secondary Objectives:

A, To determine the 3 year Overall Survival (OS) in the aspirin combined with Dabrafenib and Trametinib; B, To observe the Objective Response Rate (ORR) of aspirin combined with Dabrafenib and Trametinib; C, To observe the Disease Control Rate (DCR) in aspirin combined with Dabrafenib and Trametinib; D, To observe the fever-reducing rate of aspirin combined with Dabrafenib and DabrafenibTrametinib E, To observe the risk of coronary events in patients with aspirin combined with Dabrafenib and Trametinib.

Subjects were treated with aspirin in combination with trametinib and dalafenib. The subject will be observed on the drug for 36 months, unless the subject develops tumor progression (deterioration) or a toxic reaction that is difficult to tolerate.

Treatment drug: Dabrafenib 150 mg BID, Trametinib 2 mg QD, Aspirin 100 mg/tablet, 1 tablet/time, QD.

Dabrafenib or trametinib should be interrupted or adjusted in time if a participant developed toxicity during treatment. In case of severe drug toxicity, the participant must discontinue the drug.. If the subject develops therapeutic toxicity of Asprin during the administration, the investigator shall interrupt or adjust the dose of aspirin in a timely manner. If serious drug toxicity occurs, the subject must stop taking the drug.

Evaluate the Efficacy and Safety of Aspirin in Combination With Trametinib and Dabrafenib

An Observational Phase II Study to Evaluate the Efficacy and Safety of Aspirin in Combination With Trametinib and Dabrafenib in Advanced Non-small Cell Lung Cancer Patients With BRAF V600E Mutation

Univariate analysis of the relationship between lung cancer and treatment regimens: DFS and OS were used to compare whether there was a statistical difference (P-value less than or equal to 0.05) in the overall survival curve between the experimental and control groups by log-rank test; Multifactor analysis: PFS and OS will use a COX-proportional hazard model to estimate the hazards ratio and explore other factors that influence efficacy.

Security analysis data sets will be used for analysis. descriptive statistics, adverse events (AE), laboratory test results (blood biochemistry, liver and kidney function, coagulation and stool routine, etc.) and important vital signs (such as blood pressure) were mainly used to summarize and analyze the list.

Progression-free survival (PFS) was calculated in 36 patients treated with aspirin combined with Dabrafenib and Trametinib

Refers to the proportion of patients with fever from the beginning of treatment to the end of follow-up.

3 year Overall Survival (OS) was calculated in 36 patients treated with aspirin combined with Dabrafenib and Trametinib

The Objective Response Rate (ORR) was calculated in 36 patients treated with aspirin combined with Dabrafenib and Trametinib. ORR will be analyzed using tests, and logistic regression methods will be used to explore other factors that influence the outcome.

The Disease Control Rate (DCR) was calculated in 36 patients treated with aspirin combined with Dabrafenib and Trametinib. DCR will be analyzed using tests, and logistic regression methods will be used to explore other factors that influence the outcome.

Risk of coronary events was calculated in 36 patients treated with aspirin combined with Dabrafenib and TrametinibTrametinib

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination of Metformin With Gefitinib to Treat NSCLC	NCT01864681	NSCLC EGFR Gene Ampli... Advanced Cancer Stage IIIB NSCL... Stage IV NSCLC	Gefitinib and M... Gefitinib and p...	18 Years - 75 Years	Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Dose/ Schedule Finding Trial of Romiplostim for Chemotherapy-Induced Thrombocytopenia (CIT) in Non-Small Cell Lung Cancer (NSCLC)	NCT00413283	Lung Cancer Chemotherapy-In... Non-Small Cell ... Cancer Lung Neoplasms Oncology Solid Tumors Thrombocytopeni...	Romiplostim Placebo Gemcitabine Carboplatin Cisplatin	18 Years -	Amgen
Combination of Metformin With Gefitinib to Treat NSCLC	NCT01864681	NSCLC EGFR Gene Ampli... Advanced Cancer Stage IIIB NSCL... Stage IV NSCLC	Gefitinib and M... Gefitinib and p...	18 Years - 75 Years	Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Evaluate the Efficacy and Safety of Aspirin in Combination With Trametinib and Dabrafenib	NCT05988697	NSCLC BRAF V600E Muta... Advanced Cancer Stage IIIB NSCL... Stage IV NSCLC	Combind asprin ...	18 Years - 75 Years	Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Dose/ Schedule Finding Trial of Romiplostim for Chemotherapy-Induced Thrombocytopenia (CIT) in Non-Small Cell Lung Cancer (NSCLC)	NCT00413283	Lung Cancer Chemotherapy-In... Non-Small Cell ... Cancer Lung Neoplasms Oncology Solid Tumors Thrombocytopeni...	Romiplostim Placebo Gemcitabine Carboplatin Cisplatin	18 Years -	Amgen

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