- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04865250
Predicting Response to Neoadjuvant ATEZOLIZUMAB Plus Carboplatin/Nab Paclitaxel in Resectable Non-squamous NSCLC (iReP)
Exploratory Study Evaluating the Potential of Immune Signature Profiling for Predicting Response in Patients With Resectable Stage II, IIIA and Select IIIB (T3N2 Only) Non-squamous Non-Small Cell Lung Cancer (NSCLC) to Neoadjuvant ATEZOLIZUMAB Plus Carboplatin/Nab Paclitaxel
Exploratory study evaluating the potential of immune signature profiling for predicting response in patients with resectable Stage II, IIIA and select IIIB (T3N2 only) non-squamous Non-Small Cell Lung Cancer (NSCLC) to neoadjuvant ATEZOLIZUMAB plus Carboplatin/nab Paclitaxel
Atezolizumab is given as intravenous infusion at a fixed dose of 1200 mg, day 1 of each 21-day cycle (every 3 weeks) for 3 cycles during the neoadjuvant treatment phase, Carboplatin at an initial dose of AUC 5 mg/mL/min, intravenously day 1 of each 21-day cycle for 3 cycles during the neoadjuvant treatment Phase, and Nab-Paclitaxel (Abraxane) at 100 mg/m2, intravenously day 1, 8 and 15 of each 21-day cycle for 3 cycles during the neoadjuvant treatment phase. Surgery after the 3rd cycle Atezolizumab / Carboplatin / Nab-Paclitaxel is standard procedure.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
In early stages of non-small cell lung cancer (NSCLC), surgical treatment with curative intent is the treatment of choice. Adjuvant chemotherapy is standard of care for fully resected stage II, IIIA, or select IIIB [T3N2] NSCLC to improve survival outcome as compared to surgery alone. Neoadjuvant platinum-based chemotherapy has become a widely accepted alternative therapy. Chemotherapy regimens used in the adjuvant and neoadjuvant settings consist of platinum-based doublets. With the successful development of cancer immunotherapy in advanced NSCLC, several (neo)adjuvant studies of anti-PD-1/PD-L1 inhibitors are currently being conducted in resectable early-stage NSCLC.
The IREP study explores neoadjuvant immunochemotherapy with three cycles of atezolizumab, carboplatin and nab-paclitaxel in patients with histologically confirmed and resectable non-squamous NSCLC Stage II, IIIA or select IIIB (T3N2 only). The primary endpoint of the study is the Major Pathologic Response (MPR) rate (≤10% residual viable tumor cells) at surgery. Secondary endpoints include EFS and OS, safety endpoints as well as analyses of molecular and immunological biomarkers that are predictive of response to the neoadjuvant immunochemotherapy treatment.
Atezolizumab is given as intravenous infusion at a fixed dose of 1200 mg day 1, carboplatin at an initial dose of AUC 5 mg/mL/min intravenously day 1 and nab-paclitaxel at 100 mg/m2 intravenously day 1, 8 and 15 of each 21-day cycle (every 3 weeks) for 3 cycles during the neoadjuvant treatment phase. Subsequent surgery is standard procedure with standard lobectomy / bi-lobectomy with systematic lymph node dissection.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Dirk Jäger, Prof. med.
- Phone Number: +49 6221 56 7229
- Email: Dirk.Jaeger@med.uni-heidelberg.de
Study Contact Backup
- Name: Martin Eichhorn, PD Dr. med.
- Phone Number: +496221 396 1101
- Email: Martin.Eichhorn@med.uni-heidelberg.de
Study Locations
-
-
BaWü
-
Heidelberg, BaWü, Germany, 69126
- Recruiting
- Thoraxklinik Heidelberg gGmbH
-
Principal Investigator:
- Martin Eichhorn, PD Dr. med.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Informed consent, patients age ≥ 18-year-old including, signed and dated
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Histologically confirmed NSCLC of non-squamous histology, cStage II, IIIA or select IIIB (T3N2 only); for T-status ≤ T3 allowed; for N2 patients only IIIa1-3 Robinson classification allowed
- Deemed surgically resectable with curative intent by an attending thoracic surgeon after adequate staging including PET-CT
- Adequate lung and cardiac function for intended lung resection according to German S3 regulation
- Radiologically measurable disease as defined by response evaluation criteria in solid tumors RECIST v1.1
- Sufficient availability of the tissue sample from primary tumor before start of neoadjuvant treatment
- Females of child-bearing potential must agree to use, and be able to comply with, effective contraception (</=1% failure rate annually) without interruption, 28 days prior to starting therapy (including dose interruptions), and while on study medication or for a period of 120 days after the last dose of study medication
- Females must have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy.
- Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following treatment discontinuation, even if he has undergone a successful vasectomy.
adequate renal, hepatic, and bone marrow function as defined below
- Absolute neutrophil count (ANC) > 1500/μl
- Platelet count ≥ 100000/μl
- Hemoglobin ≥ 9 g/dl (can be post-transfusion)
- International normalized ratio (INR) ≤ 1.4 in patients not receiving anticoagulation; for patients receiving respective anticoagulation an INR ≤3.0 allowed
- Activated partial thromboplastin time (aPTT) ≤ 1.5 times upper limit of normal (ULN) in patients not receiving anticoagulation; for patients receiving respective anticoagulation a PTT ≤2.5 ULN allowed
- Bilirubin < 1.5 times ULN (for patients with known Gilbert disease Bilirubin ≤ 3 times ULN allowed)
- ALT and AST < 2.5 times ULN
- Creatinine ≤ 1.5 ULN or calculated creatinine clearance > 60 ml/min for subjects with creatinine levels > 1.5 ULN; for patients meeting the criterion of creatinine ≤ 1.5 ULN also a calculated creatinine clearance of > 30 ml/min is mandatory
Exclusion Criteria:
- Illness or condition that may interfere with a patient's capacity to understand, follow, and/or comply with study procedures
- Treatment in any other clinical trial within 30 days before screening.
- NSCLC Stage cT4
- NSCLC stage cN3 or cN2 IIIA4 (bulky or fixed multi-station N2 disease) according to Robinson classification
- NSCLC of squamous cell histology
- Any prior therapy for lung cancer (including systemic therapy, radiotherapy or major surgery)
- Malignancies other than NSCLC within 5 years prior to study inclusion with the exception of malignancies with a negligible risk of metastasis or death (5-year OS > 90%) like localized prostate cancer, ductal carcinoma in situ, adequately treated carcinoma in situ of the cervix, Stage I uterine cancer or non-melanoma skin carcinoma
- History of allogeneic tissue / solid organ transplant or allogeneic stem cell transplantation
- Patients with active hepatitis B or C infections or a history of HIV infection
- Pregnant or lactating women
- Active autoimmune disease or history of severe autoimmune disease or immunodeficiency or a syndrome that requires systemic steroids or immunosuppressive agents
The following exceptions are granted:
- patients with vitiligo, eczema, lichen simplex or resolved childhood asthma/atopy
- subjects requiring intermittent use of bronchodilatators or local steroid injections
- patients with hypothyroidism stable on hormone replacement
- Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to Cycle 1, Day 1 (except low-dose steroids for adrenal failure or emesis prophylaxis)
- History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia, drug-induced pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan
- Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
- Live vaccine within 30 days prior to first dose of trial treatment
- Cerebrovascular accident within the past 6 months
- Severe infection or significant traumatic injury within the past 4 weeks
Clinically significant history of cardiovascular disease, including any of the following:
- Myocardial infarction or unstable angina within the past 6 months
- New York Heart Association class II, III-IV congestive heart failure
- Poorly controlled cardiac arrhythmia despite medication, except rate-controlled atrial fibrillation
- Known allergy or hypersensitivity to any component of the chemotherapy regimen Patients who have been incarcerated or involuntarily institutionalized by court order or by the authorities, as well as patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: treatment
ATEZOLIZUMAB; Carboplatin; Nab-Paclitaxel
|
Immune checkpoint blockade antibody ATEZOLIZUMAB directed against PD-L1 (Programmed death-ligand 1); Carboplatin; Nab-Paclitaxel
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response to neoadjuvant immunochemotherapy with ATEZOLIZUMAB, Carboplatin and nab-Paclitaxel
Time Frame: up to 5 months (after 9 weeks of neoadjuvant immunochemotherapy (3 cycles with 21 days per cycle) + surgery (4-8 additional weeks after completion of neoadjuvant immunochemotherapy)
|
determined by Major Pathologic Response (MPR) (≤10% residual viable tumor cells) (pathologic regression grading according to Junker criteria) rate
|
up to 5 months (after 9 weeks of neoadjuvant immunochemotherapy (3 cycles with 21 days per cycle) + surgery (4-8 additional weeks after completion of neoadjuvant immunochemotherapy)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rate according to RECIST 1.1 criteria
Time Frame: pre-surgery after completion of neoadjuvant immunochemotherapy
|
determined by Δ tumor size and Δ lymph node size
|
pre-surgery after completion of neoadjuvant immunochemotherapy
|
Response rate as determined by Δ PETactivity
Time Frame: pre-surgery after completion of neoadjuvant immunochemotherapy
|
determined by standardized uptake value [SUV]
|
pre-surgery after completion of neoadjuvant immunochemotherapy
|
Event-free survival (EFS)
Time Frame: up to 29 months after study inclusion; calculated from start of 1st cycle of neoadjuvant treatment, thus including three 21 day cycles+surgery, follow-up for 24 months after end of treatment visit; end of treatment visit takes place 6 weeks after surgery
|
time to any of the following events, whichever occurs first: progression of disease prior to surgery as defined by RECIST v1.1, local or distant disease recurrence, or death due to any cause
|
up to 29 months after study inclusion; calculated from start of 1st cycle of neoadjuvant treatment, thus including three 21 day cycles+surgery, follow-up for 24 months after end of treatment visit; end of treatment visit takes place 6 weeks after surgery
|
Overall survival (OS)
Time Frame: up to 29 months after study inclusion; calculated from start of 1st cycle of neoadjuvant treatment, thus including three 21 day cycles+surgery, follow-up for 24 months after end of treatment visit; end of treatment visit takes place 6 weeks after surgery
|
time to death due to any cause
|
up to 29 months after study inclusion; calculated from start of 1st cycle of neoadjuvant treatment, thus including three 21 day cycles+surgery, follow-up for 24 months after end of treatment visit; end of treatment visit takes place 6 weeks after surgery
|
Number of patients attaining surgery as planned
Time Frame: up to 5 months
|
number of patients attaining surgery divided by the total number of patients included
|
up to 5 months
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Carboplatin
- Paclitaxel
- Atezolizumab
Other Study ID Numbers
- iReP
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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