NSCLC Stage IV
Conditions
Brief summary
Multicentre, phase II, open-label, single-arm study evaluating the preliminary efficacy, safety and tolerability of atezolizumab in association with palliative radiotherapy in adult patients diagnosed with advanced (stage IV) NSCLC, irrespective of PD-L1 status, and who have oligoprogressed to both immunotherapy with an anti PD-1 agent (e.g., pembrolizumab or nivolumab) and 1 line of chemotherapy.
Detailed description
Atezolizumab will be administered at a fixed dose of 1,200 mg by intravenous infusion every 21 days on an outpatient basis according to the its approved prescribing information. Palliative radiation therapy will be delivered concomitant to the 2nd dose of atezolizumab as a single fraction of 8 Gy to all eligible metastatic and primary sites.
Interventions
DRUGAtezolizumab
Intravenous infusion every 21 days, until disease progression, intolerance or loss of clinical benefit.
Sponsors
Ente Ospedaliero Cantonale, Bellinzona
Istituto Cantonale di Patologia
Clinical Trial Unit Ente Ospedaliero Cantonale
Oncology Institute of Southern Switzerland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed Informed Consent Form 2. Male or female aged ≥ 18 years 3. Ability to comply with the procedures of the study protocol, in the investigator's judgment 4. Histologically or cytologically confirmed diagnosis of metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 8th edition 5. No sensitizing EGFR mutation (L858R or exon 19 deletions), ALK fusion oncogene or ROS1 rearrangement detected 6. Progressing to one line of chemotherapy defined as follows:a) A platinum-doublet. b) In case of patients being ineligible for platinum-containing regimens but otherwise compliant with the other inclusion-
Exclusion criteria
of the present study, at least one line of mono-chemotherapy is required. c) As an exception, patients with oligoprogression to anti PD-1 agents alone for whom the investigator considers local treatment of metastases and continuation of immunotherapy appropriate (i.e. would not be eligible for 2nd line treatment) may be enrolled without a previous line of chemotherapy. In this case, approval by the Project Leader is necessary. 7. Progressing to an anti-PD-1 agent, either associated to chemotherapy or as monotherapy (e.g., pembrolizumab or nivolumab) 8. Life expectancy ≥ 8 weeks 9. Patients with treated, asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: 1. Measurable disease outside CNS. 2. Only supratentorial and cerebellar metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord). 3. No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed. 4. No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to initiating study treatment. 5. No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study. 6. Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to initiating study treatment, if all other criteria are met, including clinical confirmation of no evidence of interim disease progression 10. Measurable disease by RECIST v1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation and the previously irradiated lesion is not the only site of disease. 11. Oligoprogressive disease defined as follows: 1. A minimum of 1 and a maximum of 4 progressing lesions (with up to 3 total organs and 3 lesions per organ, except skeletal lesions) as assessed by a Positron Emission Tomography-Computed Tomography (PET-CT) scan (contrast enhanced). 2. Definition of progression is made by RECIST 1.1 criteria (new lesions or increased pre-existing ones). 12. Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to initiating study treatment: a) Absolute neutrophil count ≥ 1,500 cells/μL without granulocyte colony-stimulating factor support b) White blood cell (WBC) counts \> 2,500/μL c) Lymphocyte count \> 500/μL d) Serum albumin \> 2.5 g/dL e) Platelet count ≥ 100,000/μL without transfusion within 2 weeks of laboratory test used to determine eligibility f) Hemoglobin ≥ 9.0 g/dL, patients may be transfused or receive erythropoietic treatment to meet this criterion g) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALK) ≤ 2.5 × ULN with the following exceptions: patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN; patients with documented liver or bone metastases: ALK ≤ 5 × ULN. h) Serum bilirubin ≤ 1.5 × ULN. Patients with known Gilbert's syndrome who have serum bilirubin level ≤ 3 × ULN may be enrolled i) Serum creatinine ≤ 1.5 × ULN 13. For female patients of childbearing potential agreement to remain abstinent (refrain from heterosexual intercourse) or to use highly effective form(s) of contraceptive methods that result in a failure rate of \< 1% per year when used consistently and correctly during the treatment period and for at least 5 months after the last dose of atezolizumab. 1. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus) 2. Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, and established, proper use of hormonal contraceptives that inhibit ovulation (combined estrogen and progestogen containing hormonal contraception, or progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide), hormone-releasing intrauterine devices, and copper intrauterine devices 3. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. 4. Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drug. 5. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 3 months | Percentage of patients with a complete response or partial response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 12 months | Time in months from the first day of study treatment to the date of death |
| Progression Free-Survival | 12 months | Time in months from the first day of study treatment until the first evidence of tumour progression |
Countries
Switzerland
Outcome results
None listed