Patients on osimertinib with EGFR mutation exon 20, non-T790M in lung cancer. The position-20 trial.

Phase 1

Conditions: Patients on osimertinib with EGFR mutation exon 20, non-T790M in lung cancer. The position-20 trial.
MedDRA version: 20.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-004734-28-NL

Lead Sponsor: niversity Medical Center Groningen

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

1.Provision of informed consent prior to any study specific procedures
2.Patients must be = 18 years of age.
3.Locally advanced or metastatic non-small cell lung cancer, not amenable to curative surgery or radiotherapy
4.Presence of an EGFR exon 20, non-T790M, mutation, deletions and/or insertion only,
5.ECOG performance score of 0-2
6.Patients must have a life expectancy = 12 weeks.
7.Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria two weeks before screening:
oPost-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
oWomen under 50 years old would be consider postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
oDocumentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
•Male patients should be willing to use barrier contraception.
8.Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
9.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 which is suitable for accurate repeated measurements.
10.Brain metastasis, if asymptomatic, are allowed. In case of symptomatic brain metastasis, patient must have had radiotherapy and stable for at least 2 weeks.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1.Presence of a T790M mutation or other tumour driven mutations, translocations or amplifications (e.g. common EGFR mutations, KRAS, BRAF V600E, ALK, ROS1)
2.Patient is unwilling and unable to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
3.Previous treatment with EGFR-TKI
4.Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
5. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy or immune mediated pneumonitis or hepatitis previously treated with IO therapy.
6. 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.
7.Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable
8.Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
9. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
a.absolute neutrophil count <1.5 x 109/L; platelet count <100 x 109/L; haemoglobin <90 g/L
b.Alanine aminotransferase >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
c.Aspartate aminotransferase >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
d.Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases
e.Creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation)
16. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) > 470 msec obtained from 1 electrocardiograms, using the screening clinic ECG machine derived QTc value
- 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)
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in fir

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the efficacy (as assessed by best response) of osimertinib in patients with locally advanced or metastatic NSCLC and only an EGFR exon 20 mutation, deletion and/or insertion, which are T790M-ve.;<br> Secondary Objective: -Treatment efficacy<br> -Safety endpoints<br> ;Primary end point(s): Best response defined by RECIST 1.1 ;Timepoint(s) of evaluation of this end point: Until progression of disease

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): -Progression free survival (PFS) is defined by RECIST 1.1 <br> -Duration of response<br> -Overall survival<br> -Treatment- related adverse events (CTC-AE, Vs4.0)<br> ;<br> Timepoint(s) of evaluation of this end point: RECIST 1.1 assessments every 6 weeks (relative to first dose of multiple dosing), until week 24; then every 12 weeks. <br> Safety follow-up will be done continuously during treatment until 28 +/-7 days following the discontinuation of osimertinib<br>

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