A study comparing the efficacy and safety of osimertinib when given in combination with chemotherapy versus osimertinib alone in patients with locally advanced or metastatic Non-Small Cell Lung Cancer
- Conditions
- Patients with locally-advanced or metastatic EGFRm (Ex19del and/or L858R) Non-Small Cell Lung Cancer.Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-508800-39-00
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 544
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol., WHO PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks., Life expectancy >12 weeks at Day 1., At least 1 lesion, not previously irradiated that can be accurately measured at baseline as =10 mm in the longest diameter (except lymph nodes, which must have a short axis of =15 mm) with CT or MRI, and that is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumor assessment scans., Female patients who are not abstinent (in line with the preferred and usual lifestyle choice of the patient) and intend to be sexually active with a male partner must be using highly effective contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of IP or must have evidence of nonchild-bearing potential by fulfilling 1 of the following criteria at screening: a. Post-menopausal, defined as more than 50 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments b. Women under 50 years old would be considered as postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution c. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation., Male patients must be willing to use barrier contraception., Provision of signed and dated, written informed consent form prior to any mandatory study-specific procedures, sampling, and analyses., For patients who agree to the optional genetic testing, provision of signed and dated genetic testing section of the written Main ICF prior to collection of a sample for genetic analysis for inclusion in the optional genetic research as allowed by local regulations., Male or female, at least 18 years of age; patients from Japan at least 20 years of age., Pathologically confirmed nonsquamous NSCLC. NSCLC of mixed histology is allowed., Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC (per Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology), not amenable to curative surgery or radiotherapy., The tumor harbors 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations, which may include T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing., Mandatory provision of a baseline plasma sample and an unstained, archival tumor tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status., Patients must have untreated advanced NSCLC not amenable to curative surgery or radiotherapy. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agen
Spinal cord compression and unstable brain metastases. Patients with stable brain metastases who have completed definitive therapy, are not on steroids, and have a stable neurological status for at least 2 weeks after completion of the definitive therapy and steroids can be enrolled. Patients with asymptomatic brain metastases can be eligible for inclusion if in the opinion of the Investigator immediate definitive treatment is not indicated., Prior treatment with an EGFR-TKI, Major surgery within 4 wks of the 1st dose of IP. Procedures such as placement of vascular access, biopsy via mediastinoscopy or biopsy via video assisted thoracoscopic surgery are permitted, Radiotherapy treatment to more than 30% of the bone marrow/with a wide field of radiation within 4 wks of the 1st dose of IP, Current use of (or unable to stop use prior to receiving the 1st dose of study treatment) medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4 (at least 3 wks prior), Participation in another clinical study with an investigational product during the 4 wks prior to Day 1. Patients in the follow-up period of an interventional study are permitted, Involvement in the planning &/or conduct of the study (applies to both AZ staff & staff at the study site), Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions & requirements, Previous treatment allocation (safety run in)/randomization (randomization period) in the present study, Currently pregnant (confirmed with positive preg. test)/breastfeeding, History of hypersensitivity to active or inactive excipients of IP or drugs with a similar chemical structure/class to IP, Past medical history of ILD, drug induced ILD, radiation pneumonitis that required steroid treatment/any evidence of clinically active ILD, In addition, the following are considered criteria for exclusion from the exploratory genetic research: Prior allogeneic bone marrow transplant, Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection, In addition, the following are considered criteria for exclusion from the exploratory genetic research: Prior allogeneic bone marrow transplant, Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection, Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. Active infection will include any patients receiving treatment for infection., Any of the ff: cardiac criteria a.Mean resting corrected QT interval >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value b.Any clinically important abnormalities in rhythm, conduction/morphology of resting ECG; eg, complete left bundle branch block, 3rd degree heart block, 2nd degree heart block c.Any factors that increase the risk of QTc prolongation/risk of arrhythmic events such as electrolyte abnormalities including serum/plasma potassium, magnesium & calcium below the LLN, heart failure, congenital long QT syndrome, family history of long QT syndrome/unexplained su
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method