Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Daniela Wolkersdorfer

Bernd Lamprecht, MD

Georg Pall, MD

Richard Greil, MD

Lung cancer is the second most common cancer in Austria with 2.868 men and 2.009 women diagnosed in 2016. Reflecting the high mortality of this disease, 2.415 men and 1.534 women died from lung cancer. Therefore, lung cancer is the most common reason for cancer associated death in men and second most common reason in women.

This malignant disease can be divided into two main groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC is a paradigm for personalized medicine, with an increasing number of targetable gene alterations. Despite this growing diversity of molecular subtypes, in most patients no targetable mutation can be detected. For these patients check-point inhibitors with or without chemotherapy is the mainstay of the initial tumor therapy. Until recently, little progress has been made in the treatment of SCLC in last decades. Recently, an overall survival benefit by the addition of an immune-checkpoint inhibitor to first-line chemotherapy for advanced SCLC has been reported.

Despite the progress in the treatment of NSCLC, the performance of predictive biomarkers is weak. Therefore, the development of more precise prediction models is of great importance for the progress of personalized treatment strategies.

This registry is designed as multicenter observational cohort of patients with lung cancer. Patient medical, testing and treatment information will be obtained through extraction of data from existing patient medical charts. Longitudinal follow-up data, including survival and tumor progression, will also be extracted from patient medical charts. This patient follow-up data will be obtained until patient death or loss to follow-up.

For documentation in the registry, no further diagnostic or therapeutic measures are required than those already necessary in general. Participation in the registry must not interfere with treatment routines. Only routine data, which has already been recorded in the patient's medical chart, is transferred to the electronic Case Report Forms. To maintain patient confidentiality, each patient will be assigned a unique patient identifying number upon enrollment; this number will accompany the patient's medical and other registry information throughout the lifetime of the registry.

A written consent must be obtained prior to the input of data. No informed consent is required from deceased patients.

Data will be collected from all sites willing to participate.

Lung Cancer Registry

To describe the general characteristics of advanced or metastatic stage patients in Austria (Stage III A-C and IV A-B NSCLC, limited disease (LD) and extensive disease (ED) SCLC)

To describe molecular testing in patients with advanced or metastatic lung cancer

* number of patients with molecular testing
* methods for molecular testing
* number of patients with PD-L1 testing

  * PD-L1 % range per disease stage
  * PD-L1 test antibody used
* number of genes tested
* number of patients with at least one mutation identified
* number of patients with at least one druggable target identified

To describe and characterize subgroups

* Number of patients with NSCLC
* Number of patients that receive immune-checkpoint inhibitors
* Number of patients with targetable/druggable mutations

To describe degree of treatment response in %

To describe sequence of use of various treatments

To describe patient outcome by means of overall survival (OS) in %

To describe patient outcome by means of progression free survival (PFS) in %

To describe number of patients with toxicity of treatment with a focus on immune related adverse events

Arbeitsgemeinschaft medikamentoese Tumortherapie

Rare Diseases

Small Cell Lung Carcinoma

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Antibodies

Etoposide

Antibodies, Bispecific

Etoposide phosphate

Immunoglobulins

Enzyme Inhibitors

Subjects receive AK112 plus Etoposide and Carboplatin every 3- week cycle (Q3W) for 4 cycles followed by AK112 until progression.

AK112

Etoposide intravenous infusion was administered at a dose of 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4)

Shun Lu, Professor

Phase Ib open label, multicenter study to evaluate the efficacy and safety of anti-PD-1 and VEGF bispecific antibody (AK112) combined with chemotherapy in patients with ES-SCLC.

Small cell lung cancer (SCLC) is an aggressive type of neuroendocrine tumor with the majority of patients (about 60-70%) being diagnosed with metastatic disease and with a median survival ranging from 7 to 12 months. Combination chemotherapy , namely a platinum and etoposide-based regimen, represents the cornerstone of treatment for extensive stage SCLC(ES-SCLC). Despite this the duration of response is short and nearly all patients develop disease relapse or progression. The recent approval of atezolizumab in combination with carboplatin and etoposide as first line in patients with ES- SCLC is surely a step forward in the understanding the molecular landscape and treatment of this complex tumor, but new therapeutic approaches need to be explored.This trial aims to assess the safety and efficacy of a new therapeutic strategy that combines to carboplatin and etoposide, and a new drug AK112.The treatment will start with an induction phase during which eligible patients will receive, by intravenous way, a combination of the above mentioned drugs according to a specific administration regimen. This phase will last about 12 weeks. Thereafter the treatment will proceed with a maintenence phase lasting for a maximum of 24 months during which the patients will receive only AK112, by intravenous way. Treatment will be discontnued in case of until the toxicity became intolerable, the investigator determined that there was no further clinical benefit (based on a combination of RECIST V1.1 imaging assessment and clinical status), 24 months of treatment was completed, or the study was withdrawn for other reasons. During the study period the patients will undergo to periodic visits and laboratory, radiologic assessments to monitor the efficacy and the safety of the ongoing treatment.

Anti-PD-1 and VEGF Bispecific Antibody AK112 in Combination With Chemotherapy in Patients With ES-SCLC

Phase Ib Clinical Study of Anti-PD-1 and VEGF Bispecific Antibody AK112 in Combination With Etoposide and Carboplatin for the First-line Treatment of Patients With Extensive Stage Small Cell Lung Cancer

Frequency and severity of adverse events measured according to NCI Common Toxicity Criteria Adverse Event (CTCAE), version 5.0

ORR is proportion of subjects with complete response(CR) or partial response(PR). Tumor responses will be evaluated according to RECIST 1.1 criteria. Patients with no tumor assessment after baseline will be classified as non-responders.

DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST V1.1

PFS is defined as the time from the date of first dosing till the first documentation of disease progression (per RECIST v1.1) assessed by the investigator or death due to any cause (whichever occurs first)

OS is the time from the date of randomization or first dosing date to death due to any cause.

Akeso

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Patients of group A will be received 1x10\^7 DLL3-CAR-NK cells infusion treatment.

Patients of group B will be received 1x10\^8 DLL3-CAR-NK cells infusion treatment.

Patients of group C will be received 1x10\^9 DLL3-CAR-NK cells infusion treatment.

Patients of Group A will be received 1x10\^7 DLL3-CAR-NK cells infusion treatment，of group B will be received 1x10\^8 DLL3-CAR-NK cells infusion treatment，and of group C will be received 1x10\^9 DLL3-CAR-NK cells infusion treatment.

DLL3-CAR-NK cells

Liang Liu, M.D

Xiubao Ren, M.D, Ph.D

Liang Liu, MD.

Xiubao Ren, MD. PhD.

Dingzhi Huang, M.D

This is a multicenter, open-label, phase I clinical trial aimed to evaluate the safety and efficacy of DLL3-CAR-NK cells treatment for relapsed and refractory extensive small cell lung cancer (ES-SCLC).

This study is a multicenter, single arm, open-label, non randomized, single dose, dose escalation, phase I clinical trial on relapsed and refractory ES-SCLC. The phase I clinical trial will be conducted according to the principle of "3 + 3". Three dose groups will be set up, namely group A: 1.0 × 10\^7, group B: 1.0 × 10\^8, and group C: 1.0 × 10\^9 DLL3-CAR-NK cells. 9-18 subjects will be enrolled in the groups and given a single infusion of DLL3-CAR-NK cells injection in order to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), evaluate the safety and efficacy of the cell infusion. It well be recommend dose for phase II clinical study (recommended phase II dose, RP2D).

Study of DLL3-CAR-NK Cells in the Treatment of Extensive Stage Small Cell Lung Cancer

A Multicenter Phase I Trial on the Safety and Preliminary Efficacy of DLL3-CAR-NK Cells in the Treatment of Relapsed / Refractory Extensive Stage Small Cell Lung Cancer

Tianjin Medical University Cancer Institute and Hospital

Durvalumab

Antibodies, Monoclonal

Antineoplastic Agents, Immunological

Immunologic Factors

This trial is single-armed IIb stage clinical trial to study the efficacy and safety of Alotinib Plus Durvalumab-Platinum-Etoposide in First-line Treatment Extensive Small-cell Lung Cancer . We use the outcome of CASPIAN trial as control group. The primary endpoint is ORR according to the RECIST 1.1, and secondary endpoints are PFS, OS, satety and life quality.

Alotinib Plus Durvalumab-Platinum-Etoposide in First-line Treatment Extensive Small-cell Lung Cancer

Yanqiu Zhao, MS

Baoxia He, MS

Small Cell Lung cancer (SCLC) is a highly aggressive tumor that accounts for about 15 percent of all lung cancer cases. SCLC disease progresses rapidly, and about 2/3 of the patients have extensive stage (ES-SCLC) at the time of diagnosis, with extremely poor prognosis. However, the overall survival (OS) of ES-SCLC patients was not significantly prolonged, with platinum combined with etoposide chemotherapy as the standard treatment. In recent years, the emergence of Immune checkpoint inhibitor (ICI) has made the treatment of ES-SCLC appear at the dawn. In Impower133 study, Atezolizumab combined with chemotherapy significantly prolonged OS(median OS 12.3 months vs 10.3 months, HR=0.70, 95%CI 0.54-0.91, P = 0.007). Durvalumab combined with chemotherapy (CASPIAN study) is the first study in 20 years in which the total survival time of ES-SCLC treated by first-line therapy is 13 months, and there is no significant increase in adverse reactions compared with chemotherapy. Therefore, in 2019, NCCN also recommended Atezolizumab or Durvalumab+ EC regimens as a category 1 preferred option for first-line treatment of ES-SCLC.

Small Cell Lung cancer (SCLC) is a highly aggressive tumor that accounts for about 15 percent of all lung cancer cases. SCLC disease progresses rapidly, and about 2/3 of the patients have extensive stage (ES-SCLC) at the time of diagnosis, with extremely poor prognosis. However, the overall survival (OS) of ES-SCLC patients was not significantly prolonged, with platinum combined with etoposide chemotherapy as the standard treatment. In recent years, the emergence of Immune checkpoint inhibitor (ICI) has made the treatment of ES-SCLC appear at the dawn. In Impower133 study, Atezolizumab combined with chemotherapy significantly prolonged OS(median OS 12.3 months vs 10.3 months, HR=0.70, 95%CI 0.54-0.91, P = 0.007). Durvalumab combined with chemotherapy (CASPIAN study) is the first study in 20 years in which the total survival time of ES-SCLC treated by first-line therapy is 13 months, and there is no significant increase in adverse reactions compared with chemotherapy. Therefore, in 2019, NCCN also recommended Atezolizumab or Durvalumab+ EC regimens as a category 1 preferred option for first-line treatment of ES-SCLC.

Although THE TMB of SCLC is higher in solid tumors, the objective remission rate (ORR) of SCLC using PD-1 or PD-L1 inhibitors is slightly lower than that of non-small cell lung cancer, and frequent drug resistance becomes the bottleneck of treatment. Some recent studies have shown that anti-angiogenesis drugs can also reverse the immunosuppressive state of tumor microenvironment while anti-tumor therapy, and improve the efficacy of ICI, so as to play a synergistic role. Therefore, anti-angiogenesis therapy combined with immunotherapy is expected to be a new strategy for the treatment of SCLC. Amlotinib is a multi-target anti-angiogenic drug, which has been approved for third-line treatment of SCLC with mild adverse reactions. Anlotinib combined with Durvalumab may have a synergistic antitumor effect, but no studies have been reported so far. Therefore, on the basis of the CASPIAN research study, we designed the Durvalumab + chemotherapy + ernesto, first-line treatment for extensive stage small cell lung cancer with single arm, open, multicenter, phase II clinical research, expected in domestic five cancer center, into the group of 120 ES - SCLC patients with untreated, research Durvalumab + chemotherapy + ROM for efficacy and safety of Ann, and further explore the curative effect of predictive biomarkers.

Durvalumab+ Anlotinib + Standard Chemotherapy in First-line Treatment of Extensive Small-cell Lung Cancer: a Single-arm, Single-center, Phase II Clinical Study

The primary Objective of this observational study was to evaluate the Overall Survival(OS) of Durvalumab+ chemotherapy + anlotinib regimen in first-line treatment of ES-SCLC

Henan Cancer Hospital

Head of Oncology

Cisplatin

Toripalimab 240mg,d1,q3w+Anlotinib 12mg/d,d1-14,q3w+Etoposide 100mg/m2,d1-3,q3w+Cisplatin 75mg/m2 or Carboplatin AUC=5, d1, q3w,4-6 cycles in total. After the end of the first-line treatment, patients with CR, PR, and SD can continue to maintenance treatment with Toripalimab 240mg,d1,q3w+Anlotinib 12mg/d, was taken orally for 2 weeks and stopped for 1 week until the disease progressed.

Toripalimab

Anlotinib 12 mg/d,d1-14,q3w,4-6 cycles in total. In maintenance treatment period, Anlotinib 12 mg/d,d1,Oral for 2 weeks and stop for 1 week.

Anlotinib

Dong Wang, PH.D

To evaluates the effectiveness and safety of Toripalimab combined with Anlotinib and chemotherapy for the first-line treatment of ES-SCLC, and maintenance therapy are Toripalimab combined with Anlotinib.

Toripalimab Combined With Anlotinib, Etoposide and Platinum in the Treatment of Extensive-stage Small Cell Lung Cancer

Clinical Study of Toripalimab Combined With Anlotinib, Etoposide and Platinum in the Treatment of Extensive-stage Small Cell Lung Cancer

Any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment

Defined as the time interval from randomization to death. If the patient continues to survive or his life or death is unknown, the date of death will be reviewed using the latest point in time when the patient is still alive.

It is defined as the number of cases achieving CR, or PR, as a percentage of patients with evaluable efficacy. Disease remission and progress will be evaluated based on RECIST standards.

The percentage of cases that achieved remission (PR+CR) and stable disease (SD) after treatment accounted for the number of evaluable cases. In short, DCR=CR+PR+SD. And the RECIST standard is to maintain at least 4 weeks.

It is defined as the time interval from randomization of patients to disease progression or death, whichever comes first. There was no progress or the time of disease progression was not recorded when the trial was withdrawn, and the date of the last examination was used as the end date.

Third Military Medical University

Atezolizumab

Immune Checkpoint Inhibitors

Four 21-day cycles of induction therapy with atezolizumab+carboplatin+etoposide followed by 21-day cycles of maintenance therapy with atezolizumab.

Martin Reck, Prof. Dr.

Small cell lung cancer (SCLC) is a rapidly proliferating, neuroendocrine tumor that accounts for about 15% of all lung cancers. Most patients have metastases at primary diagnosis involving sites like bone, adrenal glands, liver and brain.

Compared with non-small-cell lung cancer (NSCLC) SCLC has a unique natural history with a shorter doubling time, higher growth fraction, earlier development of widespread metastases, and uniform initial response to chemo- or radiotherapy.

The combination of cis- or carboplatin and etoposide is the standard of care in the first-line treatment of stage IV (extensive-disease) SCLC (ED-SCLC). Despite response rates of 50-80%, most patients relapse within six months and the median survival time is less than 10 months. Between 14 and 23% of SCLC patients develop brain metastases.

New cytotoxic agents as well as targeted therapies have not been able to show any improvement of survival in this group of patients.

Early phase trials of PD 1/PD L1-blocking immunotherapeutic agents in patients with recurrent or ED SCLC have shown promising response rates and good tolerability. Immunotherapy may also contribute to the efficacy of systemic treatment by maintaining initial responses to chemotherapy. A double-blind, placebo-controlled phase 3 trial indicates that the addition of atezolizumab to standard chemotherapy significantly improves overall survival and progression-free survival compared with chemotherapy alone in treatment-naïve patients with ED-SCLC who are in good general condition (ECOG 0 or 1). However, about one in three SCLC patients has a poor performance status (ECOG≥2), which is associated with even shorter survival times of under eight months. At present, there is little information regarding the feasibility, safety and efficacy of adding atezolizumab to standard chemotherapy for this considerable fraction of patients.

The investigators expect, that atezolizumab in addition to chemotherapy is feasible in patients with stage IV SCLC and reduced performance status and therefore crucial efficacy data can be acquired in this trial to evaluate a putative Phase III transition in this particular patient population.

Patients With ES-SCLC and ECOG PS=2 Receiving Atezolizumab-Carboplatin-Etoposide

Single-Arm Phase II-Study in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) With Poor Performance Status Receiving Atezolizumab-Carboplatin-Etoposide

OS is defined as the length of time from first dose of experimental IMP (or first dose of chemotherapy, whichever occurs first) to the date of death. A subject who has not died will be censored at last known date alive.

ORR is defined as the proportion of All Treated Subjects whose best overall response (BOR) from baseline is either a CR or PR per RECIST 1.1 criteria. BOR is determined by the best response designation recorded between the base-line assessment (must precede the date of first dose of IMP) and the date of objectively documented progression. For subjects without documented progression, all available response designations will contribute to the BOR determination. Among All Treated Subjects the ORR (based on investigator assessments according to RECIST 1.1) will be summarized by binomial response rates and their corresponding two-sided 95% exact CIs using Clopper-Pearson method.

PFS is defined as the time from first dose of IMP to the date of the first documented tumor progression, based on investigator assessments (per RECIST 1.1), or death due to any cause.

The incidence of treatment-emergent adverse events, serious adverse events and laboratory abnormalities leading to treatment discontinuation will be used as an indicator for safety and tolerability of the IMP. Toxicities in these incidents will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

QoL questionnaires (EORTC-QLQ-C30, i.e. European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire with 30 questions for patients with cancer) will be analyzed according to the respective recommendations and manuals (scoring and interpretation materials) issued by the creators of the instruments.

Patients have to answer 28 questions from "not at all" (1) to "very much" (4), where lower scores mean a better outcome. The last two questions range from "very poor" (1) to "excellent" (7), where higher scores mean a better outcome.

QoL questionnaires (PRO-CTCAE, i.e. Patient Reported Outcome - Common Terminology Criteria for Adverse Events) will be analyzed according to the respective recommendations and manuals (scoring and interpretation materials) issued by the creators of the instruments.

Patients have to answer 22 questions either ranging from "none", "mild", "moderate", "severe" to "very severe" or from "not at all", "a little bit", "somewhat", "quite a bit" to "very much". Lower values mean a better outcome.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lung Cancer Registry	NCT04654364	Lung Cancer NSCLC Stage IV NSCLC, Stage II... SCLC, Extensive... SCLC, Limited S...		18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie
Lung Cancer Registry	NCT04654364	Lung Cancer NSCLC Stage IV NSCLC, Stage II... SCLC, Extensive... SCLC, Limited S...		18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie
Anti-PD-1 and VEGF Bispecific Antibody AK112 in Combination With Chemotherapy in Patients With ES-SCLC	NCT05116007	SCLC, Extensive...	AK112 Etoposide Carboplatin	18 Years - 75 Years	Akeso
Study of DLL3-CAR-NK Cells in the Treatment of Extensive Stage Small Cell Lung Cancer	NCT05507593	SCLC, Extensive...	DLL3-CAR-NK cel...	18 Years - 75 Years	Tianjin Medical University Cancer Institute and Hospital
Alotinib Plus Durvalumab-Platinum-Etoposide in First-line Treatment Extensive Small-cell Lung Cancer	NCT04660097	SCLC, Extensive...	Alotinib Plus D...	18 Years - 75 Years	Henan Cancer Hospital
Toripalimab Combined With Anlotinib, Etoposide and Platinum in the Treatment of Extensive-stage Small Cell Lung Cancer	NCT04731909	SCLC, Extensive... Lung Cancer Small Cell Lung...	Toripalimab Anlotinib Cisplatin Carboplatin	18 Years - 75 Years	Third Military Medical University
Patients With ES-SCLC and ECOG PS=2 Receiving Atezolizumab-Carboplatin-Etoposide	NCT04221529	SCLC, Extensive...	Atezolizumab	18 Years -	AIO-Studien-gGmbH
Study of DLL3-CAR-NK Cells in the Treatment of Extensive Stage Small Cell Lung Cancer	NCT05507593	SCLC, Extensive...	DLL3-CAR-NK cel...	18 Years - 75 Years	Tianjin Medical University Cancer Institute and Hospital
Patients With ES-SCLC and ECOG PS=2 Receiving Atezolizumab-Carboplatin-Etoposide	NCT04221529	SCLC, Extensive...	Atezolizumab	18 Years -	AIO-Studien-gGmbH

Spots Global Cancer Trial Database for sclc, extensive stage