Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Recurrence

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Amino Acids

Mitogens

Tyrosine Kinase Inhibitors

Dacomitinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

30mg of oral dacomitinib is administered daily for one cycle. After one cycle, a toxicity assessment will be conducted. Subjects will then continue dacomitinib at either 30mg or 45mg.

Daniel Tan, BSc, MBBS, PhD

This is a multi-national, multi-centre, single-arm, open-label, Phase 2 clinical study of the efficacy and safety of first-line treatment with dacomitinib, with or without dose titration, in subjects with newly diagnosed stage IIIB/IIIC/IV or recurrent EGFR-mutation-positive non-small cell lung cancer (NSCLC).

National Cancer Centre Singapore is the lead sponsor acting in a coordinating capacity and the rest of the participating sites are sponsors of their own individual sites.

Phase 2 Study of Dacomitinib in NSCLC

A Single-arm, Open-label, Phase 2 Study of Dacomitinib With or Without Dose Titration for the First-line Treatment of Locally Advanced or Metastatic Non-small Cell Lung Cancer in Subjects With an Epidermal Growth Factor Receptor (EGFR) Activation Mutation

Percentage of subjects with PFS at 12 months

Proportion of subjects with a best overall response of either complete response (CR) or partial response (PR)

Proportion of subjects with a best overall response of either CR or PR of intracranial disease

Pfizer

National Cancer Centre, Singapore

Antineoplastic Agents

Antibodies

Docetaxel

Antibodies, Bispecific

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Patients receive anlotinib 6mg/8mg/10mg qd 2W/3W and cadonilimab IV over 90 minutes on day 1. Patients also receive docetaxel 60-75 mg/m2 IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cadonilimab

Anlotinib

Baohui Han, M.D

Wei Zhang, M.D

lejie Cao, M.D

Jing Wang

Zhuang Yu, M.D

Jianya Zhou, M.D

Jing Wang, M.D

This phase Ib/II trial studies how well cadonilimab combined with anlotinib and docetaxel work in treating patients with non-small cell lung cancer that is stage IV or has come back. Cadonilimab, a PD-1/CTLA-4 bispecific antibody, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Anlotinib can regulate tumor microenvironment. Docetaxel was used in standard of care chemotherapy for non-small cell lung cancer, work to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cadonilimab, anlotinib and docetaxel together may work better in treating patients with non-small lung cancer compared to standard of care.

PRIMARY OBJECTIVES:

1. Dose discovery stage: evaluate the safety of cadonilimab combined with anlotinib and docetaxel in the treatment of locally advanced and metastatic NSCLC after failure of treatment with PD-L1/1 inhibitors and the recommended dose of anlotinib.
2. Dose expansion stage: evaluate the 6-month PFS rate of patients with locally advanced and metastatic NSCLC after failure of treatment with PD-L1/1 inhibitors by cadonilimab combined with anlotinib and docetaxel, which was evaluated by researchers based on RECIST v1.1.

SECONDARY OBJECTIVES:

1. evaluate the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), duration of response (DoR), time to response (TTR), and total survival (OS) of patients with locally advanced and metastatic NSCLC after failure of treatment with PD-L1/1 inhibitors with cadonilimab, anlotinib, and docetaxel.
2. evaluate the safety and tolerability of cadonilimab combined with arotinib and docetaxel in the treatment of locally advanced and metastatic NSCLC after failure of treatment with PD-L1/1 inhibitor.

OUTLINE:

This is a prospective, open, single-arm, multi-center, phase I b/II clinical study. All patients were confirmed Locally advanced (stage IIIB/IIIC) that cannot be resected by radical surgery and cannot accept radical synchronous/sequential radiotherapy and chemotherapy or metastatic (stage IV) NSCLC by histology or cytology. Patients must have progressed on at most a PD-1/L1 inhibitor and a platinum-based chemotherapy (combined or sequential, regardless of sequence), and at least two cycles of PD-1/L1 inhibitor (combined or non-combined chemotherapy) with clinical benefits (PFS ≥ 3 months). The study is divided into two parts. The first part is the dose discovery stage. The patients will receive a 21-day observation period of dose limiting toxicity (DLT). 3-6 subjects will be enrolled in each dose, and finally evaluate the safety and determine the recommended dose (RP2D) for phase II clinical study according to the "3+3" principle. We will continue to recruit 44 patients at the dose expansion stage.

Cadonilimab in Patients (Pts) With Advanced Non-small Cell Lung Cancer (NSCLC)

A Phase Ib/II Trial of Cadonilimab (PD-1/CTLA-4 Bispecific Antibody) in Combination With Anlotinib and Docetaxel in Patients (Pts) With Checkpoint Inhibitor (CPI)-Experienced Advanced Non-small Cell Lung Cancer (NSCLC)

Will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Overall toxicity incidence as well as toxicity profiles will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses. Proportion of acute and late toxicity will be reported, and 95% confidence intervals will be estimated using the Clopper-Pearson method.

Will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be reported and its 95% confidence intervals will be estimated using the Clopper-Pearson method. PFS rates of two patient groups stratified by binary biomarker (PD-L1 and KRAS status), respectively will be estimated with the Kaplan-Meier method and compared using the log-rank test, respectively. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of PD-L1 and KRAS status on the patients' PFS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.

Will be determined per RECIST 1.1 and immune-modified Response Evaluation Criteria in Solid Tumors.

OS and rates of two patient groups stratified by binary biomarker (PD-L1 and KRAS status), respectively will be estimated with the Kaplan-Meier method and compared using the log-rank test, respectively. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of PD-L1 and KRAS status on the patients' OS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.

Will be estimated using the method of Kaplan-Meier. Median and landmark time-point estimates will be based on the Kaplan-Meier estimates. The average hazard ratio (HR) will be estimated using a Cox proportional hazards model. An assessment of the proportional hazards assumption will be performed and an assessment of the time-dependent HR will be done.

The Affiliated Hospital of Qingdao University

Anhui Provincial Hospital

Zhejiang University

Shanghai Chest Hospital

chief physician

Frequency: 2 supervised exercise sessions per week.

Session Breakdown:

Duration: 60 minutes per session. Aerobic Endurance Training: 20 minutes. Strength Training: 40 minutes.

Aerobic Interval Training:

Set at 50% of maximal workload based on spiroergometry. Five sets of 2 minutes of exertion; 5 sets of 1 minute of recovery; Total exertion time: 20 minutes

Strength Training:

Muscle Groups Targeted: Major muscle groups. Sets and Repetitions: 2 sets with 8-12 repetitions.

Training Intensity:

Range: 50-80% of 1-RM (1-repetition maximum)

Frequency: 2 supervised exercise sessions per week.

Session Breakdown:

Duration: Approximately 30 minutes. Focus: Aerobic endurance training. Followed by 10 minutes of Respiratory therapy.

Endurance Training:

Method: Intervals for a balance between exertion and recovery. Intensity: Set at 50% of maximal workload based on spiroergometry.

The control group receives a one-time sports consultation with general information about daily activities and sports participation, as well as individual training recommendations. After the 12 weeks, the control group will be randomized into one of the exercise therapies.

Exercise intervention

Nico De Lazzari, M. Sc.

Mitra Tewes, PD. Dr.

Marcel Wiesweg, PD. Dr.

Miriam Götte, PD. Dr.

Eva-Maria Hüßler, Dr.

Andreas Stang, Prof. Dr.

Matthias Totzeck, Prof. Dr.

Lung cancer is one of the most common types of cancer in Germany, with 56,839 new cases and 45,072 deaths annually. Approximately 70% of patients with non-small cell lung cancer (NSCLC) are diagnosed at an advanced stage and suffer from comorbidities and symptoms such as fatigue, tiredness, and loss of strength. The standard first-line treatment for metastatic NSCLC includes platinum-based chemoimmunotherapy followed by immunotherapy maintenance. Exercise can have positive effects on symptoms such as shortness of breath, fatigue, quality of life, and physical fitness. However, there is a lack of current scientific evidence for the effectiveness of exercise in advanced lung cancer patients. No current trial investigated exercise in advanced NSCLC receiving immunotherapy so far.

The BREATH-study is a prospective 3-arm randomized controlled trial (RCT). In total, the investigators plan to recruit 104 patients. A 2:1:1 randomization will be performed with three study groups: a control group and two exercise therapy groups (strength+endurance exercise/only endurance exercise). One group receives individual endurance training and the other group a combination of individual endurance and strength training. Both treatment groups will be treated twice a week for 12 weeks. The control group will initially receive standard treatment without exercise for 12 weeks and will then be randomized into one of the other two study groups with exercise twice a week for 12 weeks. This approach allows for a sufficiently large sample for comparisons between exercise therapy and the control group, as well as between the two exercise therapy approaches.

The primary aim is to investigate the impact of exercise on V02peak. Secondarily endpoints aim to investigate changes in physical function, patient related outcomes and cardiac function before and after exercise.

BREATH is a prospective 3-arm 2:1:1 randomized controlled trial (RCT). The first arm represents the control group, which will receive the standard treatment for the first 12 weeks (recommendations for physical activity during cancer treatment). The other two arms represent the exercise groups, one group will receive individualized endurance training and the other group a combination of individualized endurance and strength training. All arms will be treated for 12 weeks. Afterwards, the patients in the control group are randomized to one of the other two study arms and then also treated twice for 12 weeks.

Exercise in Patients With Advanced Non-small Cell Lung Cancer

Better Symptom Control With Exercise in Patients With Advanced Non-small Cell Lung Cancer

We will publish a study protocol, including the statistical analysis plan, at an international peer-reviewed journal

The primary goal is to achieve an improvement in performance (VO2 peak\[ml/min/kg\]) from T0 (enrolment) to T1 (12 weeks) through exercise compared to the standard treatment. The one-sided alternative hypothesis of a larger improvement in the two treatment groups compared to the control group will be tested statistically as a confirmatory analysis.

The FACT-F is a 13-item questionnaire to assess fatigue in cancer patients. Subscale are physical well-being, social/family well-being, emotional well-being, functional well-being and the fatigue subscale. Based on the subscale the FACIT-F trial outcome index (TOI) Score range 0-108, FACT-G total score (Score range 0-108) and FACIT-F total score (Score range 0-160) can be calculated. The higher the score, the better the Quality of Life.

The EORTC QLQ Core Questionnaire is a 30-item instrument meant to assess some of the different aspects that define the quality of life of cancer patients (e.g., physical function, emotional function, symptom scales, and Quality of Life). High scores for functional scales (score 0-100) represent a high level of functioning, high scores for the global health status represent a high quality of life (score 0-100), high scores for symptom scales (score 0-100) represent a high level of symptomatology.

The LC13 is a modular supplement to the EORTC-C30 for assessment of symptoms in clinical lung. cancer trials. The scoring range is between 0 to 100, a high score indicating a high level of symptomatology.

Changes in 12-lead resting ECG, including PQ \[ms\], QRS \[ms\], and QT \[ms\] intervals

The exercise physiologist monitored adherence to the supervised sessions. Based on the absolute numbers of scheduled exercise sessions, both absolute and percentage-based adherence can be calculated and compared between study arms.

All withdrawals will be considered as dropouts, with reasons noted. Compare the total number of dropouts in each study arm. This provides a straightforward comparison of the raw dropout counts between groups. Also, calculate the percentage of participants who dropped out in each study arm relative to the total number of participants initially assigned to that arm. This allows for a comparison of dropout rates relative to the initial sample size and compared between study arms.

The recruitment rate quantifies the speed of participant enrollment for a study.

Safety analyses will be based on Adverse Events (AEs), Serious Adverse Events (SAEs) after the Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Therapy response in the next computer tomography (analogous to RECIST v1.1)

Treatment toxicity encompasses the adverse effects experienced by individuals undergoing chemotherapy and exercise regimens concurrently. These effects may manifest as physical symptoms such as fatigue, nausea, muscle weakness, and decreased immune function, which can impact overall well-being and treatment adherence. Monitoring and managing toxicity levels are crucial to ensure patient safety and optimize treatment outcomes. Additionally, integrating exercise interventions alongside chemotherapy may pose unique challenges, as physical activity can exacerbate certain side effects or interact with treatment efficacy. Therefore, careful monitoring and personalized exercise prescriptions are essential to mitigate toxicity risks and enhance the overall tolerability and effectiveness of combined therapy approaches. Toxicity will be reported with CTCAE v5.0

Change in dose or frequency during trial participation

Concentration of N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP), measured in picograms per milliliter (pg/mL) of blood

Concentration of troponin I in nanograms per milliliter \[ng/mL\] of blood.

The amount of Erythrocytes per liter \[/pl\]

Concentration of hemoglobin in the blood, measured in grams per deciliter (g/dL)

Count of leukocytes per nanoliter \[ /nl\]

Count of lymphocytes per nanoliter \[ /nl\]

Count of neutrophils per nanoliter \[ /nl\]

Concentration of C-reactive protein (CRP) in the blood, measured in milligrams per deciliter \[mg/dL\]

Concentration of cytokeratin-19 fragment (CYFRA 21-1) in nanograms per milliliter \[ng/mL\] of blood

Leg press \[kg.\], Latissimus pulldown \[kg.\], bench press \[kg.\], Crunch \[kg.\], Leg curl \[kg.\], Back extension \[kg.\]

Partial pressure of oxygen in arterial blood (PAO2 \[mmHg\])

Arterial oxygen saturation, measured as a percentage (SaO2 \[%\])

Partial pressure of carbon dioxide in arterial blood PCO2 \[mmHg\]

Base excess (BE) represents the amount of excess or deficit of base (primarily bicarbonate, HCO3-) in the blood \[mmol/l\]

Bicarbonate concentration in the blood HCO3 \[mmol/l\]

Bicarbonate Concentration in the extracellular fluid SBCe \[mmol/l\]

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 2 Study of Dacomitinib in NSCLC	NCT04027647	NSCLC Stage III... NSCLC Stage III... NSCLC Stage IV Recurrent NSCLC EGFR Positive N...	Dacomitinib	18 Years -	National Cancer Centre, Singapore
Cadonilimab in Patients (Pts) With Advanced Non-small Cell Lung Cancer (NSCLC)	NCT05816499	NSCLC Stage IV NSCLC Stage III... NSCLC Stage III...	Cadonilimab Anlotinib Docetaxel	18 Years -	Shanghai Chest Hospital
Exercise in Patients With Advanced Non-small Cell Lung Cancer	NCT06374160	Advanced Lung C... First Line Trea... Second Line Tre... NSCLC Stage IV NSCLC Stage III... Palliative Trea... NSCLC Stage III...	Exercise interv...	18 Years -	University Hospital, Essen
Cadonilimab in Patients (Pts) With Advanced Non-small Cell Lung Cancer (NSCLC)	NCT05816499	NSCLC Stage IV NSCLC Stage III... NSCLC Stage III...	Cadonilimab Anlotinib Docetaxel	18 Years -	Shanghai Chest Hospital

Spots Global Cancer Trial Database for nsclc stage iiic