Study to Determine the Effect of Food on the Blood Levels of AZD9291 Following Oral Dosing of a Tablet Formulation in Patients With Non-Small Cell Lung Cancer
Condition: Advanced Non Small Cell Lung Cancer; Advanced (Inoperable) Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: AZD9291 tablets; Pharmacokinetic sampling - AZD9291; Dietary Fasted; Dietary High Fat; Pharmacokinetic sampling - AZ5140 and AZ7550
Intervention description: AZD9291 tablets: Part A 80mg od, days 1 and 10 only. Part B 80mg od for 12 months.; Blood samples taken pre and post dosing of AZD9291 following either a period of fasting or consumption of a meal.; Fasted from 10 hours prior to dosing with 80mg AZD9291 tablet and 4 hours after dosing; Allocated breakfast prior to dosing with 80mg AZD9291 tablet; Blood samples taken pre and post dosing of AZD9291 following either a period of fasting or consumption of a meal.
Intervention MeSH terms: Osimertinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: oncology, cancer, non small cell lung cancer, anticancer drug, pharmacokinetics, AZD9291, EGFR sensitivity mutation, food effect

Summary:

      This is a 2-part study in patients with epidermal growth factor receptor mutation positive
      (EGFRm+) non-small cell lung cancer (NSCLC) whose disease has progressed on treatment with an
      epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI): Part A will
      determine the effect of food on the pharmacokinetics (PK) of AZD9291; Part B will allow
      patients further access to AZD9291 and will provide for additional safety data collection.

      Part A is a randomised, open-label, 2 treatment period crossover study in which patients will
      each receive a single oral dose of AZD9291 (1 x 80 mg tablet) at breakfast time
      (approximately 0800) in each of 2 treatment periods (once immediately following a high fat
      meal [fed], and once in the fasted state [fasted]), with a washout period of 9 days between
      doses.

      Approximately 38 patients are planned to be enrolled and dosed; at least 30 evaluable
      patients will be required to complete Part A (ie, the last PK sample in Treatment Period 2
      [TP 2] has been collected). Additional patients may be enrolled to allow for at least 30
      evaluable patients
    

Eligibility criteria:

        For inclusion in the study patients should fulfil the following criteria:

          1. Male or female, aged at least 18 years.

          2. Able to eat a high-fat meal within a 30-minute period, as provided by the study site.

          3. Histologically or, where appropriate, cytologically confirmed NSCLC.

          4. Radiological documentation of disease progression while on a previous continuous
             treatment with an EGFR TKI. In addition, other lines of therapy may have been given.
             All patients must have documented radiological progression on the last treatment
             administered prior to enrolling in the study.

          5. Confirmation that the tumour harbours an EGFR mutation known to be associated with
             EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).

          6. ECOG performance status 0-1 with no deterioration over the previous 2 weeks.

          7. Patients must have a life expectancy of ≥12 weeks, as estimated at the time of
             screening.

          8. Females should be using adequate contraceptive measures 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 amenorrhoeic for at
             least 12 months following cessation of all exogenous hormonal treatments; Women under
             50 years old would be considered post-menopausal if they have been amenorrhoeic for 12
             months or more following cessation of exogenous hormonal treatments and with
             luteinizing hormone and follicle stimulating hormone 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.

          9. Male patients should be willing to use barrier contraception, ie, condoms, until 6
             months after last study drug is taken.

        Patients should not enter the study if any of the following exclusion criteria are
        fulfilled:

          1. Participation in another clinical study with an IP during the last 14 days (or a
             longer period depending on the defined characteristics of the agents used).

          2. Treatment with any of the following: Treatment with an EGFR TKI w/in 8 days or
             approximately 5x half-life, whichever is the longer, of the first dose of study
             treatment; Any cytotoxic chemotherapy, investigational agents or other anticancer
             drugs w/in 14 days of the first dose of study treatment; Major surgery (excluding
             placement of vascular access) within 4 weeks of the first dose; Radiotherapy with a
             limited field of radiation for palliation within 1 week of the first dose of study
             treatment, with the exception of patients receiving radiation to more than 30% of the
             bone marrow or with a wide field of radiation which must be completed within 4 weeks
             of the first dose of study treatment; 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 CYP2C8 and of CYP3A4 (at least 1 week
             prior) and potent inducers of CYP3A4 (at least 3 week prior). 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, CYP2C8, and/ or CYP1A2.

          3. Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade,
             or other products containing grapefruit or Seville oranges within 7 days of the first
             administration of the IP until the end of Part A.

          4. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of
             starting study treatment with the exception of alopecia and Grade 2, prior platinum
             therapy related neuropathy.

          5. Patients unable to fast for up to 14 hours.

          6. Spinal cord compression or brain metastases unless asymptomatic, stable and not
             requiring steroids for at least 4 weeks prior to start of study treatment.

          7. 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 study or which would jeopardise
             compliance with the protocol, or active infection including hepatitis B, hepatitis C
             and human immunodeficiency virus. Screening for chronic conditions is not required.

          8. Patients with type I diabetes.

          9. Patients unable to swallow orally administered medication or patients with
             gastrointestinal disorders or significant gastrointestinal resection likely to
             interfere with the absorption of AZD9291.

         10. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required
             steroid treatment, or any evidence of clinically active ILD.

         11. Women who are breastfeeding.

         12. Patients with a known hypersensitivity to AZD9291

         13. Inadequate bone marrow reserve or organ function as demonstrated by any of the
             following laboratory values: Absolute neutrophil count (ANC) <1.5 x 109/L; Platelet
             count <100 x 109/L; Haemoglobin <90 g/L; ALT >2.5 x the institutional ULN if no
             demonstrable liver metastases or >5 x institutional ULN in the presence of liver
             metastases; AST >2.5 x institutional ULN if no demonstrable liver metastases or >5 x
             institutional ULN in the presence of liver metastases; Total bilirubin >1.5 x
             institutional ULN if no liver metastases or >3 x institutional ULN in the presence of
             documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases;
             Creatinine >1.5 x institutional ULN concurrent with creatinine clearance <50 mL/min
             (measured or calculated by Cockcroft-Gault formula); confirmation of creatinine
             clearance is only required when creatinine is >1.5 x institutional ULN.

         14. Any of the following cardiac criteria: Mean resting corrected QT interval corrected
             for heart rate using Fridericia's correction factor (QTcF) >470 msec obtained from 3
             ECGs; Any clinically important abnormalities in rhythm, conduction or morphology of
             resting ECG eg, complete left bundle branch block, third degree heart block, second
             degree heart block, PR interval >250 msec; Any factors that increase the risk of QTc
             prolongation or risk of arrhythmic events such as heart failure, hypokalaemia,
             congenital long QT syndrome, family history of long QT syndrome or unexplained sudden
             death under 40 years of age or any concomitant medication known to prolong the QT
             interval.

         15. For optional genetic research: Previous allogenic bone marrow transplant or
             non-leukocyte depleted whole blood transfusion within 120 days of the date of the
             genetic sample collection.