11C-osimertinib-PET/CT to identify T790M positive tumor lesions in patients that are T790M negative in a single tumor biopsy and a circulating tumor DNA sample

Completed

Conditions: lung cancer
non-small cell lung carcinoma
10027476
10029107

Registration Number: NL-OMON48936

Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

For inclusion in the study subjects should fulfil the following criteria:;1. Have a histologically or cytologically confirmed diagnosis of stage IV NSCLC, characterized by a sensitizing EGFR mutation ;2. Have progressive disease according to RECIST 1.1 on a first or second generation EGFR TKI and still receiving the drug. ;3. For phase I of the study patients should be T790M double negative (n<=4) or double positive (n<=8). For phase II of the study patients should be T790M double negative (n<=36).;4. Provision of informed consent prior to any study specific procedures;5. Patients must be > 18 years of age.;6. World Health Organization (WHO) performance status 0-2.;7. Patients must have a life expectancy * 12 weeks.;8. For phase II of the study patients must be willing to undergo a (11C-osimertinib PET/CT guided) second biopsy. ;9. Females should be using adequate contraceptive measures, should not be breastfeeding 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 at screening:;* Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments;* Women under 50 years old would be considered postmenopausal if 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 for the institution;* Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation;10. Male patients should be willing to use barrier contraception (see Restrictions, Section 3.5).;11. 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.;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 which is suitable for accurate repeated measurements.

Exclusion Criteria

1. Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site);2. Previous treatment with osimertinib;3. Treatment with an investigational drug within five half-lives of the compound;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 inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior) (Appendix A). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4. For detailed information, see section 5.1.4 of the IB for drug interaction potential. In vitro studies have demonstrated that the phase 1 metabolism of AZD9291 is predominantly via CYP3A4/5. ;5. Any unresolved toxicities from prior therapy greater than CTC AE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.;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 jeopardise 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 CNS metastases who are neurologically unstable;8. Past medical history of 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:;* Absolute neutrophil count <1.5 x 10^9/L. ;* Platelet count <100 x 10^9/L.;* Haemoglobin <90 g/L.;* 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.;* Aspartate aminotransferase >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases.;* 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.;* Creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.;10. Any of the following cardiac criteria:;* Mean resting corrected QT interval (QTc using Fredericia*s formula) >470 mSec.;* 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 first degree relatives or any concomitant medication known to prolong the QT interval. ;11. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate resorption o

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Quantitative PET derived uptake parameters in tumor lesions.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>PET-data fitting by kinetic modelling<br /><br>Objective response rate assessed with RECIST 1.1, disease control rate after 3<br /><br>months, progression-free survival, overall survival.<br /><br>Safety of 11C-osimertinib as a PET-tracer and osimertinib treatment: (S)AEs<br /><br>according to CTC AE 4.03</p><br>