There are 12 clinical trials
This study will test if local therapies in addition to erlotinib can improve responses and delay the time until new treatment is required. This study will also collect blood samples for research blood tests.
At least five patients will need to complete local therapy within 2 years of the study being open to accrual for the primary endpoint to be met.. Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion): - all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology - all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion. --- L858R --- --- G719A ---
- Any medical co-morbidities that would preclude surgery or radiation therapy Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion): - all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology - all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion. --- L858R --- --- G719A ---
Description: At least five patients will need to complete local therapy within 2 years of the study being open to accrual for the primary endpoint to be met.
Measure: Feasibility as Measured by at Least Five Patients Will Need to Complete Local Therapy. Time: 2 yearsThe purpose of this study is to compare the frequency and abundance of T790M mutation among the different Clinical modes of EGFR-TKI failure.
- Investigator confirmed progression according RECIST 1.1 during EGFR-TKI treatment within 28 days of the enrollment - Activating mutation (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q) in the EGFR gene or have had at least partial response with EGFR TKI lasting ≥ 6 months - Patient must be able to comply with the protocol Exclusion Criteria: - Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined disease progression for more than 28 days while on previous EGFR-TKI treatment. --- G719A ---
Description: The investigators will describe the number of T790M mutation on ctDNA detected by ARMS assay in patients with non-small cell lung cancer (NSCLC) resistant to tyrosine kinase inhibitors (TKIs).
Measure: Number of Patients With T790M Mutation Detected by Amplification Refractory Mutation System (ARMS) Assay Time: up to 2 yearsDescription: The investigators will describe the abundance of T790M mutation on ctDNA detected by ddPCR assay in patients with NSCLC resistant to TKIs.
Measure: Abundance of T790M Mutation Detected by Digital Droplet PCR (ddPCR) Assay in Each Individual Patient Time: up to 2 yearsDescription: The investigators will describe the number of participants with T790M mutation in each different clinical mode of TKI failure by ARMS and ddPCR, and employ chi-square test to analyze the distribution of T790M mutation by ARMS and ddPCR in patients among the different Clinical modes of TKI failure.
Measure: Number of T790M Mutation by ARMS and ddPCR Assays in Each Different Clinical Modes of TKI Failure Time: up to 2 yearsDescription: The investigators will employ Analysis of Variance (ANOVA) method to analyze the differences of T790M mutation by ddPCR in patients among the different Clinical modes of TKI failure.
Measure: Differences of T790M Mutation by ddPCR Among the Different Clinical Modes of TKI Failure Time: up to 2 yearsLung cancer is the most common cancer in the world and the leading cause of cancer-related deaths in Western countries. Unfortunately, at the time of diagnosis, the majority of patients already have metastatic disease and a systemic, palliative treatment is the primary therapeutic option. Guidelines for PS 2 patients or older than 75 years old patients at the time of diagnosis recommend for fit patients a carboplatin doublet chemotherapy. Nivolumab has proven efficacy in 3rd line squamous cell lung carcinoma and is superior to chemotherapy in 2nd line treatment of squamous and non-squamous lung cancer in term of overall survival. In 1st line, nivolumab failed to show superiority compared to a platin based doublet in terms of progression free survival and overall survival in tumors ≥ 5% PD-L1 expression. The association Nivolumab plus Ipilimumab showed encouraging results in first line setting in phase 1 study. The investigators think that with regard to the manageable toxicity of nivolumab in lung cancer population and the possibility to obtain long responses, this association could be a valid option for this population of elderly and/or PS2 patients in term of overall survival.
- Known activating mutation of EGFR (del LREA exon 19, mutation L858R or L861X of exon 21, mutation G719A/S in exon 18) or EML4-ALK or ROS-1 translocation - Superior at caval syndrome - Uncontrolled infectious status - All concurrent radiotherapy - Concurrent administration of one or several other anti-tumor therapies. --- L858R --- --- G719A ---
Description: according to RECIST 1.1
Measure: Objective response rate Time: 2 yearsDescription: according to CTCAE version 4.0
Measure: Safety Time: 2 yearsDescription: according to CTCAE version 4.0
Measure: Tolerability Time: 2 yearsDescription: according to EQ-5D questionnaire
Measure: Quality of life Time: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years maximumDescription: according to EORTC QLQ-ELD14 questionnaire
Measure: Quality of life Time: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years maximumDescription: testing by immunochemistry
Measure: PD-L1 Time: 2 yearsDescription: according to geriatric mini data set
Measure: Geriatric evaluation Time: inclusion and 2 monthsPhase II trial to evaluate trametinib in patients with locally advanced non-squamous, non-small cell lung cancer (NSCLC) whose tumors harbor a non-synonymous NF-1 mutation, with progressive disease on at least one prior line of therapy.
bevacizumab, ipilumimab) 4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). --- G719A ---
Description: The ORR is defined as the best overall response recorded from the start of the treatment until disease progression or recurrence from the start of treatment.
Measure: Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. Time: From start of treatment up to 4 years, or until disease progression, whichever comes firstDescription: The DR for Complete Response (CR) and Partial Response (PR) will be measured from the date that the best response is first recorded until the date that PD is documented. For patients who continue treatment post progression, the date of Disease Progression (PD) documentation will be used for analysis.
Measure: Duration of Response (DR) according to RECIST Version 1.1 criteria. Time: From start of treatment up to 4 years, or until disease progression, whichever comes firstDescription: DCR will be defined as the percentage of patients who have achieved CR, PR, or Stable Disease (SD) for at least 12 weeks.
Measure: Disease Control Rate (DCR) according to RECIST Version 1.1 criteria. Time: From start of treatment up to 4 years, or until disease progression, whichever comes firstDescription: PFS will be calculated as 1+ the number of days from the first dose of study drugs to documented radiographic progression or death due to any cause over a period of 1 year. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis.
Measure: Progression Free Survival (PFS) according to RECIST Version 1.1 criteria. Time: From start of treatment up to 4 years, or until disease progression, whichever comes firstDescription: OS will be calculated as 1+ the number of days from the first dose of study drugs to death due to any cause over a period of 1 year.
Measure: Overall Survival (OS) according to RECIST Version 1.1 criteria. Time: From start of treatment up to 4 years, or until disease progression, whichever comes firstA multi-centre observational, non-interventional study is to dynamically monitor the changes of circulating tumor DNA (ctDNA) in late stage NSCLC patients under Gefitinib treatment.
- Activating EGFR mutations (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q) - Able to comply with the required protocol and followed-up procedures, and able to receive oral medications Exclusion Criteria: - Histologically confirmed small cell lung cancer or other metastatic tumors - Patient had received prior chemotherapy or EGFR-TKIs treatment - Patients who harbor Exon20 T790M mutation Inclusion Criteria: - Provision of informed consent - Histologically confirmed stage IIIB/IV NSCLC. --- G719A ---
- Activating EGFR mutations (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q) - Able to comply with the required protocol and followed-up procedures, and able to receive oral medications Exclusion Criteria: - Histologically confirmed small cell lung cancer or other metastatic tumors - Patient had received prior chemotherapy or EGFR-TKIs treatment - Patients who harbor Exon20 T790M mutation Carcinoma, Non-Small-Cell Lung Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases Lung Neoplasms Carcinoma Neoplasms Lung Diseases Carcinoma, Non-Small-Cell Lung Lung Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic null --- G719A ---
Non Small Cell lung cancer (NSCLC) remains the first cause of death by cancer in the World. For the patients presenting a NSCLC stage IV, the median of survival is about 15 months today. The chemotherapy with platinum is the standard treatment for these patients but immunotherapy showed these efficacy in 1st line for patients PD-L1 positive. On the other hand, the duration of treatment by immunotherapy is not clear. Indeed, prolonged responses and long survivals have been described in patients having interrupted the treatment. In the melanoma, a treatment of 6 months of ipilimumab demonstrated its efficacy. The objective of the study is to demonstrate that a treatment of 6 months followed by an observation (stop and go) is not less effective than a treatment given until progression or toxicity. This strategy would allow to decrease the accumulated toxicities, to improve the quality of life of the patients and to decrease the costs.
Exclusion Criteria: 1. Small cell lung cancer or tumors with mixt histology including a SCLC component 2. Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18) or HER exon 20 insertion (either tissue or plasma cfDNA mutation). --- L858R --- --- G719A ---
Description: Time between the date of randomization and the first date of documented progression, as determined by BICR (Blinded Independent Central Review), or death due to any cause, whichever occurs first.
Measure: Progression Free Survival (PFS1) Time: 24 months after randomization of the last subjectDescription: Time between the start date of the second line and the second date of documented progression, as determined by BICR, or death due to any cause, whichever occurs first.
Measure: Progression Free Survival (PFS2) Time: 24 months after randomization of the last subjectDescription: Time until definitive deterioration (TUDD) from the randomization time in the experimental arm B.
Measure: Quality of life Time: 24 months after randomization of the last subjectDescription: PD-L1-stained % of tumor cells will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (PD-L1) Time: 6 monthsDescription: PD-L1 H-score will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (PD-L1 H score) Time: 6 monthsDescription: CD3/CD8 tumor infiltration will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (CD3/CD8) Time: 6 monthsDescription: neutrophil tumor infiltration will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (neutrophil) Time: 6 monthsDescription: plasma concentration of different cytokines at baseline or at the randomization point, will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (cytokines) Time: 6 monthsDescription: plasma concentration of different chemokines at baseline or at the randomization point, will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (chemokines) Time: 6 monthsNon Small Cell Lung Cancer (NSCLC) remains the leading cause of death by cancer in the world. Because of the increase in lung cancer incidence with age and the increase of life expectancy, about half of the patients are patients aged 70 or older. Several clinical trials have shown the interest of adding immunotherapy to standard 1st line chemotherapy in NSCLC. Although in these studies there was not necessarily a higher age limit, in fact the proportion of included patients aged 75 or older remains low (between 7 and 10%). It is therefore necessary to conduct a trial dedicated to these patients in order to determine whether immunotherapy is as effective and tolerated as in the general population.
Exclusion Criteria: 1. Small cell lung cancer or tumors with mixt histology including a SCLC component 2. Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18) or HER2 exon 20 insertion (either tissue or plasma cfDNA mutation). --- L858R --- --- G719A ---
Description: Time from randomization until death due to any cause
Measure: Overall Survival Time: 11 months after randomization of the last subjectDescription: Time from randomization to first observation of progression (according to RECIST v1.1) or date of death (from any cause).
Measure: Progression-free survival Time: 11 months after randomization of the last subjectDescription: Best response according to RECIST v1.1 from start to end of study treatment
Measure: Best overall response rate Time: 11 months after randomization of the last subjectDescription: Time from documentation of tumor response to disease progression
Measure: Duration of response Time: 11 months after randomization of the last subjectThe purpose of this study is to determine whether continuing erlotinib beyond disease progression in combination with chemotherapy is beneficial for NSCLC patients who have EGFR mutant disease or who have responded to EGFR TKI.
- Investigator confirmed progression according RECIST 1.1 during EGFR TKI treatment within 28 days of the randomization - Activating mutation (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q) in the EGFR gene or have had at least partial response with EGFR TKI lasting ≥ 6 months - Performance status: WHO 0-2 - Measurable disease according to RECIST 1.1 - Patients must be able to comply with study treatments - Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study - Neutrophils ≥ 1'000/μl, Platelets ≥ 100'000/μl, Alanine amino transferase ≤ 2.5 × Upper limit of normal (ULN) (< 5 × ULN if liver metastases), Alkaline phosphatase ≤ 2.5 × ULN (< 5 × ULN if liver metastases), Serum bilirubin ≤ 1.5 × ULN, Serum Creatinine ≤ 1.5 × ULN. - Patient must be able to comply with the protocol Exclusion Criteria: - RECIST 1.1 defined disease progression for more than 28 days while on previous EGFR TKI treatment. --- G719A ---
Description: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Measure: Safety and toxicity Time: An expected average of 52 weeks after last subject enrolled into our studyPreclinical data in lung cancer cell lines showed that EGFR mutation can potentially be a positive predictor for sensitivity to BKM120. Furthermore, when the erlotinib-resistant model H1975 (LR858 and T790M mutation) was treated with BKM120, significant tumor control was observed (Novartis internal data). Therefore, combining BKM120 with erlotinib could potentially down-modulate PI3K-Akt activity resulting in a synergistic effect on cell growth inhibition and enhancing the response to erlotinib.
These include, but are not limited to mutations in L858R (Exon 21); Exon 19 deletion; G719S, G719A, G719C mutations (Exon 19);or L861Q (laboratory report required at enrollment). --- L858R --- --- G719S --- --- G719A ---
Description: Percentage of patients who are alive and progression-free at 3 months (APF3) from first treatment.
Measure: Progression Free Survival at 3 Months Time: 3 monthsDescription: Defined as the time from first treatment until death from any cause.
Measure: Overall Survival Time: every 3 months after study treatment, projected 24 monthsDescription: Defined as the time from complete or partial response (CR or PR) until objective tumor progression. Tumor measurements will be obtained using CT scans of chest, abdomen and pelvis and assessed per RECIST v 1.1. Complete response (CR) is defined as a disappearance of all lesions; partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for progressive disease, taking as reference the smallest (nadir) sum LD since start of treatment.
Measure: Duration of Response Time: every 8 weeks for 12 months, then every 12 weeks thereafter, estimated 18 monthsDescription: Defined as the percentage of complete and partial responses (CR + PR) among all patients. Complete response (CR) is defined as a disappearance of all lesions; partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for progressive disease, taking as reference the smallest (nadir) sum LD since start of treatment.
Measure: Objective Response Rate Time: every 8 weeks for 12 months, then every 12 weeks thereafter, estimated 18 monthsDescription: Adverse events will be graded using CTCAE v4.3. and will be collected until 30 days after the discontinuation of study treatment for each participant. A non-serious adverse event is any untoward medical occurrence. A serious adverse event (SAE) is an event that meets one or more of the following: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; requires intervention to prevent permanent impairment or damage. Specific AE and SAE terms are provided in the Adverse event module.
Measure: Number of Participants With Serious and Non-serious Adverse Events as a Measure of Safety. Time: Every 2 weeks for 8 weeks, then every 8 weeks thereafter, estimated 24 monthsThis study is: - A multicenter, prospective, randomized, phase 3 trial. - To prove non-inferiority of Taxotere/Cisplatin compared to Pemetrexed/Cisplatin as a front line treatment of patients with non-squamous cell lung cancer. - 276 patients will be recruited.
Platelet >=100,000/uL, neutrophil >=1,500 /uL Creatinine <=1.5 x upper normal limit or creatinine clearance >=60 mL/min Bilirubin <=1.5 x upper normal limit, Transaminases <=2 x upper normal limit Alkaline phosphatase <=2 x upper normal limit - Written informed consent Exclusion Criteria: - Pregnancy, Lactating woman - Woman in child bearing age who refuses to do pregnancy test - Moderate or greater than grade 1 motor or sensory neurotoxicity - Hypersensitivity to taxane - Comorbidity or poor medical conditions - Other malignancy (except cured basal cell carcinoma or uterine cervical carcinoma in situ) - Concurrent treatment with other investigational drugs within 30 days before randomization - Active treatment with other anticancer chemotherapy - EGFR mutation (exon 19 deletion, L858R, L861Q, G719A/C/S) Inclusion Criteria: - Age >= 18 years old - ECOG performance status 0-2 - Non-squamous cell type non-small cell lung cancer (NSCLC) - Stage IV, Stage IIIB cannot be treated with curative intent or Relapsed after surgery or radiation therapy - No prior chemotherapy except adjuvant chemotherapy and concurrent chemoradiation treatment. --- L858R --- --- L861Q --- --- G719A ---
Platelet >=100,000/uL, neutrophil >=1,500 /uL Creatinine <=1.5 x upper normal limit or creatinine clearance >=60 mL/min Bilirubin <=1.5 x upper normal limit, Transaminases <=2 x upper normal limit Alkaline phosphatase <=2 x upper normal limit - Written informed consent Exclusion Criteria: - Pregnancy, Lactating woman - Woman in child bearing age who refuses to do pregnancy test - Moderate or greater than grade 1 motor or sensory neurotoxicity - Hypersensitivity to taxane - Comorbidity or poor medical conditions - Other malignancy (except cured basal cell carcinoma or uterine cervical carcinoma in situ) - Concurrent treatment with other investigational drugs within 30 days before randomization - Active treatment with other anticancer chemotherapy - EGFR mutation (exon 19 deletion, L858R, L861Q, G719A/C/S) Carcinoma, Non Small Cell Lung Carcinoma, Non-Small-Cell Lung Docetaxel is being used in 60mg/m2 3 weekly dosage in Japan and several east Asian institutions. --- L858R --- --- L861Q --- --- G719A ---
Description: months after beginning of first cycle chemotherapy
Measure: Progression Free Survival Time: one yearDescription: months from the beginning of first cycle chemotherapy
Measure: Overall Survival (months from the beginning of first cycle chemotherapy) Time: three yearsDescription: Toxicity using CTCAE version 4.0
Measure: Safety Profile Time: four monthsDescription: Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measure: Response rate Time: 6-7th weekTo tested if the adding of consolidative SBRT to TKI in EGFR mutated patients with less than or equal to 5 metastatic sites (primary + 5) will improve progression free survival (PFS) compared to TKI alone.
To evaluate overall survival after SBRT followed by maintenance chemotherapy in comparison to maintenance chemotherapy alone.. Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion): - all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology - all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion. --- L858R --- --- G719A ---
- Any medical co-morbidities that would preclude surgery or radiation therapy Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion): - all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology - all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion. --- L858R --- --- G719A ---
Description: Evaluate the effect of TKI with or without SBRT on progression free survival
Measure: Progression free survival Time: 4 yearsDescription: To describe local control and out-of-field disease progression
Measure: local control Time: 4 yearsDescription: To evaluate overall survival after SBRT followed by maintenance chemotherapy in comparison to maintenance chemotherapy alone.
Measure: Overall survival Time: 4 yearsThe purpose of this study is to test whether the combination of bevacizumab and erlotinib can prolong progression free survival as compared with erlotinib alone as first-line treatment in patients with non small cell lung cancer (NSCLC) with activating mutation of EGFR.
Inclusion Criteria: 1. Age ≥18 years 2. Histological documentation of primary non squamous lung carcinoma 3. Stage IV or IIIB disease with supraclavicular metastatic nodes (according to TNM 7th edition) 4. Activating epidermal growth factor receptor mutation (exon19 deletion or exon 21 L858R mutation or other activating/sensitizing mutations, such as exon 21 L861Q, exon 18 G719S, G719A and G719C, exon 20 S768I and V769L). --- L858R --- --- L861Q --- --- G719S --- --- G719A ---
Description: as determined by investigator
Measure: progression free survival Time: up to 2 yearsDescription: as determined by an independent central review board blinded to study treatment
Measure: progression free survival Time: up to 2 yearsDescription: samples taken at baseline, 6 weeks, 6 months, and at progression
Measure: number and type of EGFR mutations in plasma samples Time: up to 2 years