Immunopheresis Alone or in Combination With Paclitaxel or Atezolizumab in Non-small Cell Lung Cancer (NSCLC).
- Conditions
- Non Small Cell Lung Cancer
- Interventions
- Device: LW-02 device immunopheresis combined with atezolizumabDevice: LW-02 device immunopheresis combined with weekly paclitaxelDevice: LW-02 device immunopheresis
- Registration Number
- NCT04690686
- Lead Sponsor
- Immunicom Inc
- Brief Summary
This pilot study aims to evaluate the short-term and long-term safety, tolerability, and effectiveness of immunopheresis with the LW-02 column in removal of sTNFRs from plasma of patients with advanced, refractory NSCLC and to detect a potential disease control signal when employed in combination with low dose chemotherapy (ie, paclitaxel), immunotherapy (ie, atezolizumab) in patients who already failed first-line therapy, or as monotherapy in patients who already have failed second-line therapy.
- Detailed Description
This is an open-label, Phase 2a pilot study of Immunicom's LW-02 column- combined with low-dose chemotherapy or immunotherapy in patients who have failed first-line treatment or employed as monotherapy in patients who have failed second-line therapy-to evaluate the short-term and long-term safety, tolerability and effectiveness of these approaches in removing sTNF-Rs and the potential for disease control in advanced, refractory NSCLC patients. Along with LW-02 column immunopheresis, patients enrolled in Arm 1 will receive combination immunotherapy with atezolizumab and patients enrolled in Arm 2 also will receive combination chemotherapy with paclitaxel. Patients in Arm 3 will be treated with LW-02 column immunopheresis alone as a third-line treatment regimen, assuming the first-line treatment included a platinum salt. Following study qualification, patients will be assigned to the appropriate treatment. All patients may receive up to 48 LW-02 column-based immunopheresis treatments over a 16-week (4-month) period with up to 3 treatments per week). Importantly, each LW-02 immunopheresis treatment should last up to 3 hours and process, approximately, 2 times the patient's plasma volume (2PV).
Each patient assigned to the treatment with LW-02 column-based immunopheresis will require central vascular access for the procedure. In general, a cuffed, tunneled dual-lumen catheter will be inserted into a central vein and remain in situ throughout the 16-week treatment phase (or longer if additional treatment is clinically indicated). The catheter will be used to connect the inlet and return lines of the apheresis system to the patient. Immunopheresis treatments will be performed using the LW-02 column used inline with a centrifugal apheresis system that allows for secondary plasma processing system (eg, the Terumo BCT Spectra Optia Apheresis System® or alternate apheresis system). Proper anticoagulation of the centrifugal apheresis device is generally provided by utilizing acid citrate dextrose formula A (ACD-A).
Patients will be followed and clinically evaluated for two-years posttreatment. In Year 1, patients will be clinically evaluated at 3, 6, 9, and 12 months from the end-of-treatment (EOT) visit. In Year 2 quarterly (every 3 months) telephone contacts will be made to determine overall survival.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LW-02 device immunopheresis combined with atezolizumab LW-02 device immunopheresis combined with atezolizumab LW-02 column immunopheresis treatments \~3x/week for 16 weeks plus atezolizumab 1200 milligrams (mg) q3w until disease progression or loss of clinical benefit, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first \[N=8\] LW-02 device immunopheresis combined with weekly paclitaxel LW-02 device immunopheresis combined with weekly paclitaxel LW-02 column immunopheresis treatments \~3x/week for 16 weeks plus paclitaxel 80 mg/m2 /week × 6 followed by 2 weeks rest until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first. \[N=8\] LW-02 device immunopheresis LW-02 device immunopheresis LW-02 column immunopheresis treatments \~3x/week for 16 weeks alone until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first. \[N=8\]
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events 16 weeks Treatment-Emergent Adverse Events which will be analysed in study ill be:
1. Adverse Event (AE)
2. Serious Adverse Events (SAE)
3. Adverse Device Effect (ADE)
4. Serious Adverse Device Effect (SADE) Each of the Treatment-Emergent Adverse Events will be assessed for their seriousness, severity \[using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 v. 5.0\] and causality (relationship with the use of the investigated medical device).Column performance effectiveness 16 weeks Column efficiency and effectiveness in removal of sTNF-Rs from patient plasma without clinically-meaningful leaching of capture ligand (SC-TNF-α) - change in sTNF-R and TNF-α plasma levels from initiation to the end of each
LW-02 column perfornance effectiveness will be assessed to measure over 30 minutes (sTNF-Rs) and over the duration (leaching) of each procedure, respectively:
* Removal of soluble TNF receptor 1 (sTNF-R1)
* Removal of soluble TNF receptor 2 (sTNF-R2)
* Leaching of sc-TNF-α from the columnIncidence of Treatment-Emergent Adverse Events of special interest. 16 weeks Incidence of Treatment-Emergent Adverse Events of special interest assessment will include:
1. tumor lysis syndrome and
2. systemic inflammatory response syndrome. These events may or may not be serious and they may or may not be considered related to study treatment. Regardless of relationship or severity, these events will be recorded if they start after the first application of study treatment and will be followed until resolution.
- Secondary Outcome Measures
Name Time Method Patient functioninig with Eastern Cooperative Oncology Group (ECOG) 16 weeks Eastern Cooperative Oncology Group (ECOG) scale describes patient's functioning in terms of ability to care for themselves, daily activity, and physical ability (walking, working). The scale grades 0 to 5 (0=fully active while and 5=dead).
Quality of life assessment with EQ-5D-5L scale 16 weeks EQ-5D-5L scale to assess: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels:
from no problems to extreme problems.Quality of life assessment with EORTC-QLQ-C30 scale 16 weeks EORTC-QLQ-C30 scale measures cancer patients' physical, psychological and social functions. The EORTC QLQ-C30 comprises 30 items (i.e. single questions), 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).
Quality of life assessment with EORTC-QLQ-LC29 scale 16 weeks EORTC-QLQ-LC29 measuring the quality of life in patients with lung cancer. Each dimension in the scale has four response levels from not at all (1) to very much (4).
Clinical endpoint - overall survival 16 weeks A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the first study treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameters will be:
Overall Survival (OS). Overall survival ( OS ) is defined as the time from randomization to death from any cause, is a direct measure of clinical benefit to a patient.Clinical endpoint - progression free survival 16 weeks A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the first study treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameters will be:
Progression Free Survival (PFS) Progression-free survival ( pfs ) is defined as time from randomization until first evidence of tumour progression or until death from any cause, whichever comes first.Clinical endpoint - disease control rate 16 weeks A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the first study treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameters will be:
Disease Control Rate (DCR) Overall response rate (ORR) is defined as the proportion of patients who have a partial or complete response to therapy; it does not include stable disease and is a direct measure of drug tumoricidal activity. In contrast, disease control rate is a composite of ORR and stable disease and is useful to measure the efficacy of therapies that have tumoristatic effects rather than tumoricidal effects.Nutritional status assessment 16 weeks The Scored Patient-Generated Subjective Global Assessment (PG-SGA©) scale will be used. The Scored PG-SGA© includes the four patient-generated historical components (Weight History, Food Intake, Symptoms and Activities and Function - also known as the PG-SGA Short Form©), the professional part (Diagnosis, Age, Metabolic stress, and Physical Exam), the Global Assessment (A = well nourished, B = moderately malnourished or suspected malnutrition, C = severely malnourished) and the total numerical score.
Physical performance status assessment with 6 minute walk test (6MWT) 16 weeks The physical performance assessment will be measured with 6-minute walk test (6MWT).
6MWT meassures the distance patient covers when walking in a regular pace in standardized condition. The longer distance is expected in patients who improve while the poor patient performance and capability, the shorter distance will be measured.Muscle performance assessment with a hand grip test 16 weeks The muscle performance assessment will be measured hand grip test. The purpose of this test is to measure the maximum isometric strength of the hand and forearm muscles. The participant will be asked to squeeze the dynamometer as hard as possible with each of his or her hands in a standing position. The subject squeezes the dynamometer with maximum isometric effort, which is maintained for about 5 seconds. Results for left and right hand separately are recorded in kilograms.
Trial Locations
- Locations (3)
Acibadem Maslak Hospital, Medical Oncology Department - coordinating site
🇹🇷Istanbul, Sariyer, Turkey
Acibadem Atakent Hospital, Medical Oncology Department
🇹🇷Istanbul, Kucukcekmece, Turkey
Acibadem Altunizade Hospital, Mecical Oncology Department
🇹🇷Istanbul, Uskudar, Turkey