Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Adenocarcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Pemetrexed

Cisplatin

Nedaplatin

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

nedaplatin 90mg/m2 d1+pemetrexed 500mg/m2 d1 （Every three weeks for a treatment cycle）

cisplatin 25mg/m2 d1-3+pemetrexed 500mg/m2 d1 （Every three weeks for a treatment cycle）

cisplatin and pemetrexed

nedaplatin+pemetrexed

li-kun chen, Doctor

li-kun chen, doctor

li-kun Chen, Doctor

The purpose of this study is to investigate the PFS, ORR, OS and overall toxicity value（OTV）on advanced adenocarcinoma treated with nedaplatin or cisplatin combined with pemetrexed.

A Prospective Multi-center Phase III Randomized Controlled Trial

Nedaplatin or Cisplatin Combined With Pemetrexed in the First Line Treatment of Advanced Adenocarcinoma：A Prospective Multi-center Phase III Randomized Controlled Trial

Progression-free survival is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first

ORR is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR).

OS is defined as the time from the starting date of study drug to the date of death due to any cause

toxicity graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0

the proportion (%) of patients without disease progression at 18 weeks

Sun Yat-sen University

associate professor

Symptoms and General Pathology

Neoplasm Metastasis

Vinorelbine

Vitamin B 12

Hydroxocobalamin

Tubulin Modulators

Antimitotic Agents

Methylcobalamin

Vitamin B12

Cobalamin

Cyanocobalamin

Oral vinorelbine 60-80 mg/m2 on days 1 and 8 (first cycle 60 mg/m2) + Cisplatin 80 mg/m2 on day 1 every 3 weeks, for 4 cycles.

Maintenance with Metronomic Oral Vinorelbine 50 mg three times a week on Monday, Wednesday and Friday continuously until disease progression, patient refusal or excessive toxicity (1 cycle: 3 weeks).

Pemetrexed, 500 mg/m2, day 1 + Cisplatin, 75 mg/m2, day 1 every 3 weeks, for 4 cycles.

Maintenance with Pemetrexed 500 mg/m2 day1 q 21 until disease progression (1 cycle: 3 weeks).

7-10 days before treatment administration, premedication with vitamin B12 1000µg intramuscular injection (every 9 weeks) and folate 1mg every day should be commenced.

Oral vinorelbine 60-80 mg/m2 on days 1 and 8 (first cycle 60 mg/m2) every 3 weeks, for 4 cycles

Oral vinorelbine

Cisplatin 80 mg/m2 on day 1 every 3 weeks, for 4 cycles

Maintenance with Metronomic Oral Vinorelbine 50 mg three times a week on Monday, Wednesday and Friday continuously until disease progression, patient refusal or excessive toxicity (1 cycle: 3 weeks).

Maintenance with Metronomic Oral Vinorelbine

Pemetrexed, 500 mg/m2, day 1 every 3 weeks, for 4 cycles

Cisplatin 75 mg/m2, day 1 every 3 weeks, for 4 cycles

Maintenance with Pemetrexed 500 mg/m2 day1 q 21 until disease progression (1 cycle: 3 weeks)

Maintenance with Pemetrexed

Claudio Dazzi, MD

This is an open-label, multicentre, randomized phase II trial.

Eligible patients with Non Small Cell Lung Cancer (NSCLC) with high Thymidylate Synthase (TS) expression , will be randomly assigned with 1:1 ratio to the following treatment Arms:

A. 4 cycles of Cisplatin + Oral Vinorelbine followed by maintenance with Metronomic Oral Vinorelbine until disease progression

B. 4 cycles of Cisplatin + Pemetrexed followed by maintenance with Pemetrexed until disease progression

Treatment will be repeated every 21 days .

An Open-label, Multicenter, Randomized Phase II Trial of Treatment with Cisplatin and Pemetrexed or Cisplatin and Oral Vinorelbine in Chemotherapy Naïve Patients affected by stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer with high Thymidylate Synthase (TS)expression After signing the informed consent for TS expression evaluation (see Appendix A), patients will be tested for TS expression status of their tumor tissue.

If TS expression is more than 70 in the nucleus or ≥210 in nucleus and in the cytoplasm of tumor cell, they will be categorized as high TS expression patients, and if it is less, they will be considered as TS-negative.

Study Treatment:

Eligible patients will be randomly assigned to the following treatment Arms:

A. Oral vinorelbine 60-80 mg/m2 on days 1 and 8 (first cycle 60 mg/m2) + Cisplatin 80 mg/m2 on day 1 every 3 weeks, for 4 cycles.

Maintenance with Metronomic Oral Vinorelbine 50 mg three times a week on Monday, Wednesday and Friday continuously until disease progression, patient refusal or excessive toxicity (1 cycle: 3 weeks).

B. Pemetrexed, 500 mg/m2, day 1 + Cisplatin, 75 mg/m2, day 1 every 3 weeks, for 4 cycles.

Maintenance with Pemetrexed 500 mg/m2 day1 q 21 until disease progression (1 cycle: 3 weeks).

7-10 days before treatment administration, premedication with vitamin B12 1000µg intramuscular injection (every 9 weeks) and folate 1mg every day should be commenced.

The total duration of the study will be 3 years. The enrollment period wil be 2 years and 1 year of follow up. Treatment period: until disease progression, intolerable toxicity or patient refusal.

Number of Subjects :130 patients (65 patients per arm)

Statistical Methodology The primary variable of this study is Disease Control Rate (DCR). According to primary variable, assuming a DCR≥70% for patients with high TS expression treated with cisplatin and vinorelbine and a DCR=44% for patients with high TS expression treated with cisplatin and pemetrexed, considering a 2-tailed alpha=0.05 and beta=0.10, it is necessary to enroll 65 patients per arm (130 patients in total) in a 24-month period and the subsequent 12-month follow-up.

Open-label, Multicenter, Randomized Phase II Trial of Treatment With Cisplatin and Pemetrexed or Cisplatin and Oral Vinorelbine in Chemotherapy Naïve Patients Affected by Stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer With High Thymidylate Synthase Expression

Rate (DCR; complete response (CR) plus partial response (PR) plus stable disease (SD)). The response is assessed according to the RECIST 1.1 criteria.

Toxicity assessed after each cycle using the Common Toxicity Criteria AE (version 4.03)

Overall Survival (OS) is defined as the observed length of life from study entry to death for any cause or the date of last contact for patients lost to follow up

Progression free survival (PFS) is the time from the date of randomization to the date of the first observation of documented disease progression or death due to any cause. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation.

to define the optimal Thymidylate Synthase expression(TS) H-score cutpoint in cytoplasm and/or nucleus . TS nuclear and cytoplasmic staining will be evaluated by using an intensity scale (0-3) and the percentage of cells in each category, resulting in semiquantitative H scores ranging from 0 to 300 will be calculated. Total TS H-scores will be calculated posthoc as the sum of nuclear and cytoplasm TS H-scores (range 0-600).

Pierre Fabre Laboratories

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Pleural Neoplasms

Malignant Mesothelioma

Antibodies

Pembrolizumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Neoadjuvant pembrolizumab, followed by surgery, followed by adjuvant pemetrexed and cisplatin

Neoadjuvant pembrolizumab every 21 days for three cycles

Adjuvant chemotherapy with cisplatin and pemetrexed every 21 days for 4 cycles

Cisplatin and Pemetrexed

Buerkley Rose, RN

Bianca Hill

Hedy Kindler, M.D.

Hedy Kindler, MD

This is a single institution, single-arm, window of opportunity pilot trial of pembrolizumab in patients with resectable malignant pleural mesothelioma. All patients will undergo a pretreatment PET/CT scan for clinical staging and a VATS procedure to acquire pretreatment tissue.

Three cycles of pembrolizumab will then be administered (200 mg IV every 21 days). A PET/CT scan will then be repeated to assess response to pembrolizumab and then surgical resection will be performed at least 4 weeks after the third dose of pembrolizumab. Standard adjuvant chemotherapy consisting of cisplatin and pemetrexed for 4 cycles (every 21 days) will be given following surgery. After the completion of standard chemotherapy, optional adjuvant treatment with pembrolizumab will be given to eligible patients for 1 year post-surgery.

A Pilot Window-Of-Opportunity Study of the Anti-PD-1 Antibody Pembrolizumab in Patients With Resectable Malignant Pleural Mesothelioma

A Pilot Window-of-opportunity Study of the Anti-PD-1 Antibody Pembrolizumab in Patients With Resectable Malignant Pleural Mesothelioma

Determined using a CLIA Nanostring nCounter based profiling assay

Adverse events will be summarized by type, grade, and relationship to the study drug.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Prospective Multi-center Phase III Randomized Controlled Trial	NCT02607592	Carcinoma，Non-S...	cisplatin and p... nedaplatin+peme...	18 Years - 75 Years	Sun Yat-sen University
Open-label, Multicenter, Randomized Phase II Trial of Treatment With Cisplatin and Pemetrexed or Cisplatin and Oral Vinorelbine in Chemotherapy Naïve Patients Affected by Stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer With High Thymidylate Synthase Expression	NCT02919462	Carcinoma, Non-... Secondary Advanced Stage ... High Thymidylat...	Oral vinorelbin... Cisplatin Maintenance wit... Pemetrexed Cisplatin Maintenance wit...	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Open-label, Multicenter, Randomized Phase II Trial of Treatment With Cisplatin and Pemetrexed or Cisplatin and Oral Vinorelbine in Chemotherapy Naïve Patients Affected by Stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer With High Thymidylate Synthase Expression	NCT02919462	Carcinoma, Non-... Secondary Advanced Stage ... High Thymidylat...	Oral vinorelbin... Cisplatin Maintenance wit... Pemetrexed Cisplatin Maintenance wit...	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
A Prospective Multi-center Phase III Randomized Controlled Trial	NCT02607592	Carcinoma，Non-S...	cisplatin and p... nedaplatin+peme...	18 Years - 75 Years	Sun Yat-sen University
A Pilot Window-Of-Opportunity Study of the Anti-PD-1 Antibody Pembrolizumab in Patients With Resectable Malignant Pleural Mesothelioma	NCT02707666	Pleural Mesothe...	Pembrolizumab Cisplatin and P...	18 Years -	University of Chicago
A Pilot Window-Of-Opportunity Study of the Anti-PD-1 Antibody Pembrolizumab in Patients With Resectable Malignant Pleural Mesothelioma	NCT02707666	Pleural Mesothe...	Pembrolizumab Cisplatin and P...	18 Years -	University of Chicago

Spots Global Cancer Trial Database for cisplatin and pemetrexed