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Phase 1 Completed N=39 Other

Study to Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of AZD9291, in Patients With EGFR Positive Non-small Cell Lung Cancer. Patients Will be Chosen From Those Who Have Already Been Prescribed an EGFR TKI Medicine (Such as Iressa or Tarceva)

Non-Small Cell Lung Cancer · Advanced (Inoperable) Non Small Cell Lung Cancer
Source: ClinicalTrials.gov NCT02157883 ↗
Enrolled (actual)
39
Serious AEs
20.7%
Results posted
Apr 2016
Primary outcomePrimary: Cmax of AZD9291 — 242.5; 201.7 nM

Summary

This is a 2 part study in patients with EGFRm+ non small cell lung cancer (NSCLC), whose disease has progressed on an EGFRm TKI, who are refractory or resistant to standard therapy. Part A will assess the effect of multiple oral doses of itraconazole on the single dose pharmacokinetic (PK) parameters of AZD9291. On completion of Part A, patients may continue to take AZD9291 tablets (Part B) following the collection of the 216 hour sample on Day 19 if they and the Investigator deem it appropriate, until such time as their disease progresses, the Investigator believes they are no longer deriving clinical benefit, or they stop taking AZD9291 for any other reason

Outcome Measures

OutcomeResultp-value
PRIMARY
Cmax of AZD9291
242.5; 201.7
PRIMARY
AUC of AZD9291
13520; 17090
SECONDARY
AUC(0-120) of AZD9291
10280; 11370
SECONDARY
AUC(0-t) of AZD9291
12260; 14520
SECONDARY
Tmax of AZD9291
4.00; 6.04
SECONDARY
t1/2 of AZD9291
61.05; 78.36
SECONDARY
CL/F of AZD9291
11.84; 9.368
SECONDARY
Vz/F of AZD9291
1019; 1059
SECONDARY
Cmax of AZ5104
8.568; 5.746
SECONDARY
AUC of AZ5104
1155; 941.4
SECONDARY
Cmax of AZ7550
4.321; 1.897
SECONDARY
AUC of AZ7550
624.1; 292.1

Eligibility Criteria

For inclusion in the study, patients should fulfil the following criteria:

  • Male or female, aged at least 18 years.
  • Histological or cytological confirmation diagnosis of NSCLC.
  • Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI, eg, gefitinib or erlotinib. 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.
  • Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).
  • ECOG performance status 0-1 with no deterioration over the previous 2 weeks.
  • Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening.
  • Evidence of non-childbearing status for women of childbearing potential, or post-menopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on Day 1 of Part A, or post menopausal status. 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 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; documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
  • 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:

  • 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).
  • 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.
  • 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.
  • 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.
  • Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of stud
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02157883). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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