Phase 1
Completed N=44
Study to Assess the Effect of AZD9291 on the Blood Levels of Rosuvastatin, in Patients With EGFRm+ Non-small Cell Lung Cancer
Source: ClinicalTrials.gov NCT02317016 ↗Enrolled (actual)
44
Serious AEs
11.5%
Results posted
Jul 2016
Primary outcomePrimary: Assessment of Maximum Plasma Concentration (Cmax) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291 — 13.96; 24.03 nanogram per millilitre (ng/mL)
Summary
This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase inhibitor (TKI) agent.
Part A will assess the effect of AZD9291 on the pharmacokinetic (PK) parameters of rosuvastatin, following multiple oral dosing of AZD9291 in the fasted state.
Part B will allow patients further access to AZD9291 after the PK phase (Part A) and will provide for additional safety data collection. All patients from Part A who completed treatment may continue to receive AZD9291 80 mg once daily as a single agent until: disease progression; they are no longer deriving clinical benefit; or any other reason.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Assessment of Maximum Plasma Concentration (Cmax) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291 |
13.96; 24.03 | — |
| PRIMARY Assessment of AUC From Time Zero Extrapolated to Infinity for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291 |
139.1; 185.7 | — |
| SECONDARY Assessment of Time to Maximum Plasma Concentration (Tmax) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291 |
2.05; 2.07 | — |
| SECONDARY Assessment of Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration at Time "t" (AUC0-t) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291 |
130.6; 183.7 | — |
| SECONDARY Assessment of Apparent Plasma Clearance (CL/F) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291 |
143.8; 107.7 | — |
| SECONDARY Assessment of Apparent Volume of Distribution (Vz/F) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291 |
3890; 2874 | — |
| SECONDARY Assessment of Terminal Elimination Half-life (t1/2[lambda_z]) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291 |
18.75; 18.51 | — |
| SECONDARY Assessment of Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUCtau) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together |
15800; 1655; 1418 | — |
| SECONDARY Assessment of Maximum Plasma Concentration at Steady State (Css,Max) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together |
897.9; 86.20; 73.73 | — |
| SECONDARY Assessment of Time to Reach Maximum Plasma Concentration at Steady State (Tss,Max) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together |
5.00; 5.00; 5.05 | — |
| SECONDARY Assessment of Minimum Plasma Concentration at Steady State (Css,Min) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together |
485.6; 54.60; 46.46 | — |
| SECONDARY Assessment of Apparent Plasma Clearance at Steady State (CLss/F) for AZD9291 Following Administration of AZD9291 and Rosuvastatin Together |
10.14 | — |
| SECONDARY Assessment of the Metabolite to Parent Ratios of Css,Max (MRCss,Max) for AZ5104 and AZ7550 Following Administration of AZD9291 and Rosuvastatin Together |
0.09599; 0.08212 | — |
| SECONDARY Assessment of the Metabolite to Parent Ratios of AUCtau (MRAUCtau) for AZ5104 and AZ7550 Following Administration of AZD9291 and Rosuvastatin Together |
0.1048; 0.08971 | — |
Eligibility Criteria
For inclusion in the study patients must 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, erlotinib or afatinib. 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).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks (Appendix G).
- Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening.
- 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 luteinising hormone (LH) and follicle stimulating hormone (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.
- Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- Male patients should be willing to use barrier contraception, ie, condoms.
Exlusion Criteria:
- Participation in another clinical study with an IP in last 14 days (or longer depending on the defined characteristics of the agents used).
- Any patient of Asian ethnicity or has a parent who is of Asian ethnicity (eg, Chinese, Filipino, Japanese, Korean and Vietnamese). If only a grandparent is Asian, this is acceptable. Asian Indians are acceptable.
- Treatment w/ any of the following: an EGFR TKI (eg, erlotinib, gefitinib or afatinib) within 8 days or approx. 5 x half-life, whichever is the longer, of the first dose of study treatment; Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment; Major surgery (excluding placement of vascular access) w/in 4 weeks of the 1st dose of study treatment; Radiotherapy with a limited field of radiation for palliation w/in 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of bone marrow or with a wide field of radiation which must be completed w/in 4 weeks of the 1st 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 CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior). All patients must avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4.
- Unresolved toxicities from prior therapy > CTCAE Grade 1 at the study start besides 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 final PK sample collection on Day 35 of Part A.
- Spinal cord compres
Data sourced from ClinicalTrials.gov (NCT02317016). 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.