This study has been transitioned to CTIS with ID 2023-505981-26-00 check the CTIS register for the current data. Primary Efficacy ObjectiveThe primary efficacy objective of the study is as follows:• To evaluate the efficacy of 16 cycles of…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy outcome measure
DFS, defined as the time from randomization to the date of occurrence of any of
the following, whichever occurs first:
- First recurrence of NSCLC, as determined by the investigator after an
integrated assessment of radiographic data, biopsy sample results (if
available), and clinical status
- Occurrence of new primary NSCLC, as assessed by the investigator
- Death from any cause
This efficacy outcome measure will be assessed in PD-L1-selected subpopulations
(defined by the SP142 IHC assay) within the Stage II-IIIA subpopulation, in all
randomized patients with Stage II-IIIA NSCLC, and in the ITT population.
Secondary outcome
Secundary study parameters/outcome of the study
The secondary efficacy outcome measures for this study are as follows:
• Overal Survival, defined as the time from randomization to death from any
cause, in the ITT population
• Disease Free Survival rates at 3 years and 5 years in the PD-L1 subpopulation
and in the stage II-IIIA population and in the ITT population
• Disease Free Survival within the subpopulations within patient with Stage
II-IIIA NSCLC.
The safety outcome measures for this study are as follows:
• Incidence, nature, and severity of adverse events, serious adverse events,
and adverse events of special interest graded according to the NCI CTCAE v4.0
• Changes from baseline in vital signs, physical findings, and targeted
clinical laboratory results
• Incidence of ATA response to atezolizumab and potential correlation with PK,
pharmacodynamic, safety, and efficacy parameters
Pharmacokinetic Outcome Measures
The PK outcome measures for this study are as follows:
• Atezolizumab maximum serum concentration (Cmax) observed after infusion on
Day 1 of Cycle 1
• Atezolizumab minimum serum concentration under steady-state conditions within
a dosing interval (Cmin) prior to the infusion on Day 1 of Cycles 2, 3, 4, 8,
and 16 and at studytermination
Exploratory Outcome Measures
The exploratory outcome measures for this study are as follows:
• Status of PD-L1, immune- and NSCLC-related and other exploratory biomarkers
in tumor tissues, and blood collected before, during, or after treatment with
atezolizumab or at first evidence of radiographic disease recurrence or
confirmation of new primary NSCLC
• Status of ICs and exploratory biomarkers in biopsy specimens and blood
collected at the first evidence of radiographic disease recurrence or
confirmation of new primary NSCLC
Background summary
Adjuvant chemotherapy is the standard of care for fully resected (Stage
IB*IIIA) NSCLC. Additional studies are looking at the role of molecularly
targeted adjuvant studies in relatively uncommon molecular subsets (epidermal
growth factor receptor [EGFR], anaplastic lymphoma kinase) that account for
< 15% of NSCLC. There is currently no active adjuvant study for the general
NSCLC patient population. Atezolizumab targets human programmed death*ligand 1
(PD-L1) and inhibits its interaction with its receptors, programmed death*1
(PD-1) and B7.1 (CD80, B7-1). Both of these interactions are reported to
provide inhibitory signals to T cells. Given the evidence of the clinical
activity of atezolizumab in previously treated NSCLC, and the need to continue
to improve upon the survival for patients with resected NSCLC treated with
adjuvant cisplatin-based chemotherapy, the Sponsor proposes Study GO29527.
Study objective
This study has been transitioned to CTIS with ID 2023-505981-26-00 check the CTIS register for the current data.
Primary Efficacy Objective
The primary efficacy objective of the study is as follows:
• To evaluate the efficacy of 16 cycles of atezolizumab treatment compared with
best supportive care as measured by disease-free survival (DFS) as assessed by
the investigator in PD-L1-subpopulation within the Stage II-IIIA population, in
all randomized patients Stage II-IIIA NSCLC, and in the ITT population
Secondary Efficacy Objective
The secondary efficacy objective of the study are to evaluate the efficacy of
atezolizumab monotherapy treatment compared with BSC on the basis of the
following outcome measures
- OS in the ITT population
- 3-year and 5-year DFS rates in the PD-L1 subpopulation within the Stage
II-IIIA population, in all-randomized patients with Stage II-IIIA NSCLC, and in
the ITT population (i.e., all randomized patients in this study)
- DFS within the PD-L1-selected populations (defined by the SP263 IHC assay) in
the evaluable Stage II-IIIA subpopulation and within the evaluable ITT
population
Safety objectives
The safety objectives of the study are as follows:
• To evaluate the safety and tolerability of atezolizumab treatment after up to
four cycles of cisplatin-based chemotherapy in the adjuvant setting
• To evaluate the incidence and titers of ATAs against atezolizumab in the
adjuvant setting and to explore the potential relationship of the
immunogenicity response with pharmacokinetics, safety, and efficacy
pharmacokinetic objective
The PK objective of the study is as follows:
• To characterize the PK of atezolizumab treatment in the adjuvant setting
Exploratory Objectives
• To evaluate the relationship between tumor and blood based biomarkers
(including but not limited to PD-L1, PD-1, and others), as defined by IHC,
quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and/or
other methods
• To assess predictive, prognostic, and pharmacodynamic exploratory biomarkers
in archival and/or fresh tumor tissue and blood and their association with
disease status, mechanisms of resistance, and/or response to atezolizumab in
the adjuvant treatment setting
• To evaluate biomarkers at the time of apparent recurrence of primary disease
(i.e., NSCLC primary disease recurrence, occurrence of new primary NSCLCs) and
to distinguish any immunomodulatory activity of atezolizumab (i.e.,
pseudoprogression/tumor-immune infiltration) in patients with confirmed
recurrence of disease in patients assigned to atezolizumab.
Study design
This study is a Phase III, global, multicenter, open-label, randomized study.
Intervention
Eligible patients will go on to be randomized in a 1:1 ratio to receive either
atezolizumab (Arm A) or BSC (Arm B). In Arm A, atezolizumab will be
administered intravenously on Day 1 of each 21-day cycle. Patients randomized
to Arm B will be continually followed starting on Day 1 of each 21-day cycle.
No crossover will be allowed from Arm B to Arm A.
Study burden and risks
Many of the tests and procedures done during the study are part of the regular
medical care and would also be done if the subject was not taking part in the
study. Additional blood and urine samples will be taken for study purposes.
Electrocardiograms (ECG) will be done. CT or MRI scans will be performed more
frequent than would normally be done.
The subjects may experience side effects of the medication or experience risks
or discomforts of the study procedures (e.g. blood drawing, scans and biopsies)
The most common side effects reported with atezolizumab (occurring in 10% or
more of patients) are:
• Back pain
• Fatigue
• Joint pain (arthralgia)
• Lack of energy (asthenia)
• Decreased appetite
• Diarrhea
• Muscle and bone pain (myalgia, musculoskeletal pain and bone pain)
• Urinary tract infection
• Shortness of breath (dyspnea)
• Itching of the skin
• Nausea
• Fever
• Rash
• Vomiting
• Cough
• Headache
Grenzacherstrasse 124
Basel 4070
CH
Grenzacherstrasse 124
Basel 4070
CH
Listed location countries
Age
Inclusion criteria
- A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in
paraffin block (preferred) or 15 (or more) unstained, freshly cut, serial
sections (on slides) from an FFPE resected tumor specimen is required for
participation in this study. This specimen must be accompanied by the
associated pathology report - ECOG performance status of 0 or 1 - Histological
or cytological diagnosis of Stage IB (tumors >= 4 cm)*IIIA (T2*3 N0, T1*3 N1,
T1-3 N2, T4-N0 1) non-small cell lung cancer (NSCLC) - Eligible to receive a
cisplatin-based chemotherapy regimen - For female patients of childbearing
potential and male patients with partners of childbearing potential, agreement
(by patient and/or partner) to use a highly effective form(s) of contraception
during study treatment that results in a low failure rate of < 1% per year
when used consistently and correctly. Female and male patients should continue
contraceptive use for 6 months after the last dose of cisplatin-based
chemotherapy (cisplatin plus vinorelbine, docetaxel, gemcitabine, or
pemetrexed). Female patients treated with atezolizumab should continue
contraception use for 5 months after the last dose. Women must refrain from
donating eggs during this same period.
Exclusion criteria
- Illness or condition that may interfere with a patient's capacity to
understand, follow, and/or comply with study procedures
- Pregnant and lactating women
- Treatment with prior systemic chemotherapy, with the following exceptions:
•Chemotherapy for early stage of malignancy with curative intent, provided that
the last dose received was more than 5 years prior to enrollment, is allowed
•Low-dose chemotherapy for non-malignant conditions is allowed
- Hormonal cancer therapy or radiation therapy as prior cancer treatment within
5 years before enrollment
- Treatment with any other investigational agent with therapeutic intent within
28 days prior to enrollment
- Known sensitivity to any component of the chemotherapy regimen the patient
will be assigned to, or to mannitol
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Patients who have had prior anti-CTLA-4 treatment may be enrolled, provided
the following requirements are met:
•Last dose of anti-CTLA-4 at least 6 weeks prior to randomization
•No history of severe immune-mediated adverse effects from anti-CTLA- 4 (NCI
CTCAE Grades 3 and 4)
- Known tumor PD-L1 expression status as determined by an IHC assay from other
clinical studies (e.g., patients whose PD-L1 expression status was determined
during screening for entry into a study with anti-PD-1 or anti-PD-L1 antibodies
but were not eligible are excluded)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-505981-26-00 |
| EudraCT | EUCTR2014-003205-15-NL |
| CCMO | NL54046.100.15 |