| Eligibility |
Inclusion Criteria:
- For inclusion in the study subjects should fulfil the following criteria:
1. Provision of informed consent prior to any study-specific procedure
2. Patients must be = 18 years old
3. Locally advanced /metastatic NSCLC not responsive to surgery or radiotherapy
4. Validated activating EGFR sensitising mutations with or without T790M resistance
mutation at the time of recruitment for patients who have no prior EGFR TKI
treatment.
5. Patients must be EGFR treatment naïve.
6. ECOG Performance status is 0-1 with no deterioration over the last 2 weeks prior
to study recruitment.
7. Normal organ and bone marrow function measured within 28 days before the study as
defined below:
- Haemoglobin = 9.0 g/dL and no blood transfusions in the 28 days prior to
entry
- Absolute neutrophil count (ANC) = 1.5 x 109/L
- No features suggestive of MDS/AML on peripheral blood smear
- White blood cells (WBC) > 3x109/L
- Platelet count = 100 x 109/L
- Total bilirubin = 1.5 x institutional upper limit of normal (ULN)
- AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless
liver metastases are present in which case it must be = 5x ULN
- Serum creatinine = 1.5 x institutional upper limit of normal (ULN)
- ECOG performance status 0-2
8. A life expectancy = 12 weeks in all patients.
9. Females in childbearing age should be using adequate contraceptive measures,
should not be breastfeeding and their pregnancy test prior to the start of
treatment must be negative. Evidence of non-child-bearing potential is fulfilled
by one of the following criteria at screening:
- The post-menopausal period defined as age =50 years and amenorrheic for at
least 12 months following cessation of all exogenous hormonal treatments
- Women <50 years old they have been amenorrheic for 12 months or more
following cessation of exogenous hormonal treatments and with LH and FSH
levels in the post-menopausal range.
- Documentation of irreversible surgical sterilisation by hysterectomy,
bilateral oophorectomy or bilateral salpingectomy but not a tubal ligation
10. Male patients should be willing to use barrier contraception
11. The patient is willing to comply with the protocol during the study including
undergoing treatment and scheduled visits and examinations including follow up.
12. At least one lesion, not previously irradiated, that can be accurately measured
at baseline as = 10 mm in the longest diameter (except lymph nodes which must
have short axis = 15 mm) with computed tomography (CT) or magnetic resonance
imaging (MRI) and is considered suitable for accurate repeated measurements.
Exclusion Criteria:
- Patients should not enter the study if any of the following exclusion criteria are
fulfilled:
1. Treatment with other EGFR-TKI within 8 days or within five half-lives of the
compound before study entry whichever is the longer; any cytotoxic chemotherapy,
or other anticancer drugs against NSCLC within 14 days of study entry
2. Previously treated with an immune checkpoint inhibitor
3. Patients with second primary cancer, except: adequately treated non-melanoma skin
cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
curatively treated with no evidence of disease for = 5 years
4. Radiotherapy to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks before the study entry
5. Any unresolved toxicities from prior therapy greater than Common Terminology
Criteria for Adverse Events (CTCAE) grade 1 at the time of study treatment with
the exception of alopecia grade 2 and platinum-related neuropathy.
6. Unstable spinal cord compression/brain metastases unless asymptomatic and not
requiring steroids for at least 2 weeks prior to the start of study treatment.
For patients with brain metastases, gamma knife or stereotactic brain surgery is
allowed prior to study treatment.
7. Major surgery within 4 weeks of starting study treatment and patients must have
recovered from any effects of any major surgery. Minor surgery is allowed.
8. Patients currently receiving or unable to stop use medications or herbal
supplements that are potent inhibitors of CYP3A4 (at least 1 week prior) and
potent inducers of CYP3A4 (at least 3 weeks prior). All patients must avoid
concomitant use of any medications, herbal supplements and/or foods with known
inducer/inhibitory effects on CYP3A4 unless part of protocol treatment.
9. Severe or uncontrolled systemic diseases, including uncontrolled hypertension and
active bleeding diatheses, which based on investigator's opinion makes it
undesirable for the patient to participate in the trial or which would jeopardise
compliance with the protocol, or having active infection including hepatitis B,
hepatitis C and human immunodeficiency virus (HIV). Screening for chronic
conditions is not required.
10. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring
steroid treatment, or any evidence of clinically active ILD
11. Any of the following cardiac criteria:
1. Mean resting corrected QT interval (QTc using Fredericia's formula) > 470
msec
2. Any clinically important abnormalities in rhythm, conduction or morphology
of resting ECG (e.g., complete left bundle branch block, third-degree heart
block, second-degree heart block)
3. Any factors increasing the risk of QTc prolongation or arrhythmias such as
heart failure, hypokalaemia, congenital long QT syndrome, family history of
long QT syndrome or unexplained sudden death under 40 years of age in first
degree relatives or any concomitant medication known to prolong the QT
interval
12. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
swallow the drug or previous significant bowel resection that would preclude
adequate absorption of Osimertinib
13. History of hypersensitivity to Osimertinib (or drugs with a similar chemical
structure or class to Osimertinib) or any excipients of these agents
14. Males and females of reproductive potential who are not using an effective method
of contraception and females who are pregnant or breastfeeding or have a positive
serum pregnancy test prior to study entry
15. Judgment by the Investigator that the patient should not participate in the study
if the patient is unlikely to comply with study procedures, restrictions and
requirements
16. Previous allogeneic bone marrow transplant.
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