Carcinoma, Non-Small-Cell Lung With EGFR Mutation PositivePhase 1AURAChinaPKNCT02529995
Phase I, Study in Chinese NSCLC Patients
A Phase 1 study testing AZD9291 40 mg and AZD9291 80 mg in people with Carcinoma, Non-Small-Cell Lung With EGFR Mutation Positive, run by AstraZeneca at 2 sites in China.
Trial summary
A Phase I, Open-Label, Two Parts Study to Assess the Safety, Tolerability,Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Chinese Patients with Advanced Non-Small Cell Lung Cancer who have Progressed Following Prior Therapy with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung With EGFR Mutation Positive
- What is being tested?
- AZD9291 40 mg and AZD9291 80 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesChina
- Study dates
- 24 Aug 2015to 27 Sep 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision informed consent
- Aged at least 18 years
- Histological or cytological confirmation diagnosis of NSCLC
- Locally advanced or metastatic NSCLC
- Radiological documentation of disease progression while on a previous continuous treatment with an approved EGFR TKI. In addition other lines of therapy may have been given
- Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q)
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- World Health Organisation (WHO) performance status 0-1
- At least one lesion suitable for accurate repeated measurements
- Females
- Child bearing potential : should not be breast feeding, use adequate contraceptive measures for female patients with child-bearing potential, OR
- Have evidence of non-child-bearing potential that meet 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 below 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing 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
- Male patients should be willing to use barrier contraception ie, condoms
Who cannot join
- Treatment with any of the following (prior to first dose of study treatment)
- Treatment with an EGFR TKI within 8 days
- Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days
- Previous treatment with AZD9291, or a Thr790Met (T790M) directed EGFR TKIs
- Major surgery (excluding placement of vascular access) within 4 weeks
- Radiotherapy :
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- Within 1 week if limited field of radiation for palliation of the first dose of study treatment
- Within 4 weeks if receiving radiation to more than 30% of the bone marrow or with a wide field of radiation
- Patients currently receiving (or unable to stop use at least 1 week) medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)
- Treatment with an investigational drug within five half-lives of the compound
- 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
- Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment
- 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
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derivedQTc value
- 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, P wave to R wave (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 (Q-T interval) 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
- Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease 7, Inadequate bone marrow reserve or organs function as demonstrated by any of the following laboratory values:
- Absolute neutrophil count <1.5x109/L
- Platelet count <100x109/L
- Hemoglobin <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
- 8, 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 Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9291 9, History of hypersensitivity to active or inactive excipients of AZD9291 or drugs with a similar chemical structure or class to AZD9291 10, Women who are breast feeding 11, Involvement in the planning and conduct of the study (applies to AstraZeneca staff or staff at the study site) 12, Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Phase I, Open-Label, Two Parts Study in Chinese Patients With Advanced NSCLC Who Have Progressed Following Prior Therapy With an EGFR Tyrosine Kinase Inhibitor Agent
A Phase I, Open-Label, Two Parts Study to Assess the Safety, Tolerability,Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Chinese Patients with Advanced Non-Small Cell Lung Cancer who have Progressed Following Prior Therapy with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent
Study Objective: 1, Primary Objective To characterise the pharmacokinetics (PK) of AZD9291 and its metabolites (AZ5104 and AZ7550) after single then multiple doses of AZD9291 administered orally once daily in Chinese patients with locally advanced or metastatic non small cell lung Cancer (NSCLC) who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) agent.
2, Secondary objective(s) To investigate the safety and tolerability of AZD9291 when given orally to Chinese patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an approved EGFR TKI agent. To obtain a preliminary assessment of the anti-tumour activity of AZD9291 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
Read the detailed description
This is a phase I, open-label, two parts (Part A and Part B) study to determine the pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg and 80 mg) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an approved EGFR TKI agent (+/- additional chemotherapy regimens).
Approximately 24 patients will enter into this study, with 12 patients at each dose level.
- Cohort 1 will investigate the pharmacokinetics of single then multiple dosing of AZD9291 at 40 mg once daily dose.
- Cohort 2 will investigate the pharmacokinetics of single then multiple dosing of AZD9291 at 80 mg once daily dose.
The enrollment of Cohort 2 will start after Cohort 1 finishes the enrollment. The first 12 patients enrolled in the study will be in 40 mg dose Cohort.
Patients will be administered a single dose of AZD9291 on Day 1, Cycle 0 at the beginning of Part A period. From Day 2 to Day 6, no treatment will be given, but PK samples will be obtained; on Day 7 (Cycle1, Day1), the patients will be administered AZD9291 once daily on a continuous schedule, ie, no break in AZD9291 dosing. Part A will complete after Cycle 4 treatment and Part B will start without treatment interruption.
Patients in both cohorts should continue on treatment with AZD9291 until a treatment discontinuation criterion is met. There is no maximum duration of treatment as patients may continue to receive AZD9291 beyond RECIST 1.1 defined progression as long as they are continuing to receive clinical benefit, as judged by the investigator.
The whole study will be divided nominally into two parts: Part A will assess the pharmacokinetics and preliminary efficacy and safety of AZD9291 at 40 mg and 80 mg respectively, and Part B will assess only the safety and efficacy data of AZD9291.
Following completion of the Part A, patients will automatically continue to Part B.
- Being tested
- AZD9291 40 mg, AZD9291 80 mg
- Medical subject headings
- Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9291 40 mgDrug
This is a two parts (Part A and Part B) study to determine the pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg Cohort 1 and 80 mg Cohort 2) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens).
AZD9291 80 mgDrug
This is a two parts (Part A and Part B) study to determine the pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg Cohort 1 and 80 mg Cohort 2) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens).
| Study group | Role | What they receive |
|---|---|---|
| AZD9291 40 mg | Experimental | Cohort 1: 40 mg once daily Receives: Drug: AZD9291 40 mg |
| AZD9291 80 mg | Experimental | Cohort 2: 80 mg once daily Receives: Drug: AZD9291 80 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax of AZD9291 After Single Dosing
Pharmacokinetics of AZD9291 after single dosing by assessment of maximum plasma AZD9291 concentration
Measured: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
Cmax of AZ5104 After Single Dosing
Pharmacokinetics of AZD9291 metabolites (AZ5104) after single dosing by assessment of maximum plasma concentration
Measured: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
Cmax of AZ7550 After Single Dosing
Pharmacokinetics of AZD9291 metabolites (AZ7550) after single dosing by assessment of maximum plasma concentration
Measured: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
AUC of AZD9291 After Single Dosing
Pharmacokinetics of AZD9291 after single dosing by assessment of area under the plasma concentration time curve from zero to infinity
Measured: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
AUC of AZ5104 After Single Dosing
Pharmacokinetics of AZD9291 metabolites (AZ5104) after single dosing by assessment of area under the plasma concentration time curve from zero to infinity
Measured: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
AUC of AZ7550 After Single Dosing
Pharmacokinetics of AZD9291 metabolites (AZ7550) after single dosing by assessment of area under the plasma concentration time curve from zero to infinity
Measured: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
CL/F of AZD9291 After Single Dosing
Rate and extent of absorption of single dose AZD9291 by assessment of apparent clearance following oral administration
Measured: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
C(ss, Max) of AZD9291 After Multiple Dosing
Pharmacokinetics of AZD9291 after multiple dosing by assessment of maximum plasma concentration at steady state
Measured: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
C(ss, Max) of AZ5104 After Multiple Dosing
Pharmacokinetics of AZD9291 metabolites (AZ5104) after multiple dosing by assessment of maximum plasma concentration at steady state
Measured: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
C(ss, Max) of AZ7550 After Multiple Dosing
Pharmacokinetics of AZD9291 metabolites (AZ7550) after multiple dosing by assessment of maximum plasma concentration at steady state
Measured: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
AUC(ss) of AZD9291 After Multiple Dosing
Pharmacokinetics of AZD9291 after multiple dosing by assessment of area under the plasma concentration curve from time zero to the end of the dosing interval
Measured: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
AUC(ss) of AZ5104 After Multiple Dosing
Pharmacokinetics of AZD9291 metabolites (AZ5104) after multiple dosing by assessment of area under the plasma concentration curve from time zero to the end of the dosing interval
Measured: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
AUC(ss) of AZ7550 After Multiple Dosing
Pharmacokinetics of AZD9291 metabolites (AZ7550) after multiple dosing by assessment of area under the plasma concentration curve from time zero to the end of the dosing interval
Measured: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
CL(ss)/F of AZD9291 After Multiple Dosing
Pharmacokinetics of AZD9291 after multiple dosing by assessment of apparent plasma clearance at steady state
Measured: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
Secondary outcomes (1)
Objective Response Rate (ORR)
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (according to independent review) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.
Measured: Treatment discontinuation plus 28 days or 12 months after last subject first dose (LSFD). Results are based on data cut off of 2 Nov 2016.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2015 (estimated)
- Study start24 Aug 2015
- Primary completion28 Jan 2016
- Study completion27 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell Lung With EGFR Mutation PositiveStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02529995
- Sponsor's protocol ID
- D5160C00018
- Acronym
- AURAChinaPK
- Status last verified
- Feb 2020
- First submitted
- 6 Aug 2015
- Last updated
- 11 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Zhao H, Cao J, Chang J, Zhang Z, Yang L, Wang J, Cantarini M, Zhang L. Pharmacokinetics of Osimertinib in Chinese Patients With Advanced NSCLC: A Phase 1 Study. J Clin Pharmacol. 2018 Apr;58(4):504-513. doi: 10.1002/jcph.1042. Epub 2017 Dec 14.
PubMed 29239002
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Open-Label, Two Parts Study in Chinese Patients With Advanced NSCLC Who Have Progressed Following Prior Therapy With an EGFR Tyrosine Kinase Inhibitor Agent
- ClinicalTrials.gov ID
- NCT02529995
- Acronym / sponsor ID
- AURAChinaPK / D5160C00018
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 24 Aug 2015 (actual)
- Primary completion
- 28 Jan 2016 (actual)
- Study completion
- 27 Sep 2019 (actual)
- First posted
- 20 Aug 2015 (estimated)
- Results
- Posted 6 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase I, Open-Label, Two Parts Study to Assess the Safety, Tolerability,Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Chinese Patients with Advanced Non-Small Cell Lung Cancer who have Progressed Following Prior Therapy with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent
Study Objective: 1, Primary Objective To characterise the pharmacokinetics (PK) of AZD9291 and its metabolites (AZ5104 and AZ7550) after single then multiple doses of AZD9291 administered orally once daily in Chinese patients with locally advanced or metastatic non small cell lung Cancer (NSCLC) who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) agent.
2, Secondary objective(s) To investigate the safety and tolerability of AZD9291 when given orally to Chinese patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an approved EGFR TKI agent. To obtain a preliminary assessment of the anti-tumour activity of AZD9291 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
Detailed description
This is a phase I, open-label, two parts (Part A and Part B) study to determine the pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg and 80 mg) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an approved EGFR TKI agent (+/- additional chemotherapy regimens).
Approximately 24 patients will enter into this study, with 12 patients at each dose level.
- Cohort 1 will investigate the pharmacokinetics of single then multiple dosing of AZD9291 at 40 mg once daily dose.
- Cohort 2 will investigate the pharmacokinetics of single then multiple dosing of AZD9291 at 80 mg once daily dose.
The enrollment of Cohort 2 will start after Cohort 1 finishes the enrollment. The first 12 patients enrolled in the study will be in 40 mg dose Cohort.
Patients will be administered a single dose of AZD9291 on Day 1, Cycle 0 at the beginning of Part A period. From Day 2 to Day 6, no treatment will be given, but PK samples will be obtained; on Day 7 (Cycle1, Day1), the patients will be administered AZD9291 once daily on a continuous schedule, ie, no break in AZD9291 dosing. Part A will complete after Cycle 4 treatment and Part B will start without treatment interruption.
Patients in both cohorts should continue on treatment with AZD9291 until a treatment discontinuation criterion is met. There is no maximum duration of treatment as patients may continue to receive AZD9291 beyond RECIST 1.1 defined progression as long as they are continuing to receive clinical benefit, as judged by the investigator.
The whole study will be divided nominally into two parts: Part A will assess the pharmacokinetics and preliminary efficacy and safety of AZD9291 at 40 mg and 80 mg respectively, and Part B will assess only the safety and efficacy data of AZD9291.
Following completion of the Part A, patients will automatically continue to Part B.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD9291 40 mg | Experimental | Drug: AZD9291 40 mgCohort 1: 40 mg once daily |
| AZD9291 80 mg | Experimental | Drug: AZD9291 80 mgCohort 2: 80 mg once daily |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Provision informed consent
- Aged at least 18 years
- Histological or cytological confirmation diagnosis of NSCLC
- Locally advanced or metastatic NSCLC
- Radiological documentation of disease progression while on a previous continuous treatment with an approved EGFR TKI. In addition other lines of therapy may have been given
Key exclusion criteria (26 listed)
- Treatment with any of the following (prior to first dose of study treatment)
- 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
- Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment
- 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
- Any of the following cardiac criteria:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD9291 40 mgThis is a two parts (Part A and Part B) study to determine the pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg Cohort 1 and 80 mg Cohort 2) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens). | Drug | AZD9291 40 mg |
| AZD9291 80 mgThis is a two parts (Part A and Part B) study to determine the pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg Cohort 1 and 80 mg Cohort 2) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens). | Drug | AZD9291 80 mg |
Primary outcome
Cmax of AZD9291 After Single Dosing
Time frame: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 after single dosing by assessment of maximum plasma AZD9291 concentration
Cmax of AZ5104 After Single Dosing
Time frame: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 metabolites (AZ5104) after single dosing by assessment of maximum plasma concentration
Cmax of AZ7550 After Single Dosing
Time frame: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 metabolites (AZ7550) after single dosing by assessment of maximum plasma concentration
AUC of AZD9291 After Single Dosing
Time frame: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 after single dosing by assessment of area under the plasma concentration time curve from zero to infinity
AUC of AZ5104 After Single Dosing
Time frame: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 metabolites (AZ5104) after single dosing by assessment of area under the plasma concentration time curve from zero to infinity
AUC of AZ7550 After Single Dosing
Time frame: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 metabolites (AZ7550) after single dosing by assessment of area under the plasma concentration time curve from zero to infinity
CL/F of AZD9291 After Single Dosing
Time frame: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.
Rate and extent of absorption of single dose AZD9291 by assessment of apparent clearance following oral administration
C(ss, Max) of AZD9291 After Multiple Dosing
Time frame: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 after multiple dosing by assessment of maximum plasma concentration at steady state
C(ss, Max) of AZ5104 After Multiple Dosing
Time frame: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 metabolites (AZ5104) after multiple dosing by assessment of maximum plasma concentration at steady state
C(ss, Max) of AZ7550 After Multiple Dosing
Time frame: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 metabolites (AZ7550) after multiple dosing by assessment of maximum plasma concentration at steady state
AUC(ss) of AZD9291 After Multiple Dosing
Time frame: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 after multiple dosing by assessment of area under the plasma concentration curve from time zero to the end of the dosing interval
AUC(ss) of AZ5104 After Multiple Dosing
Time frame: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 metabolites (AZ5104) after multiple dosing by assessment of area under the plasma concentration curve from time zero to the end of the dosing interval
AUC(ss) of AZ7550 After Multiple Dosing
Time frame: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 metabolites (AZ7550) after multiple dosing by assessment of area under the plasma concentration curve from time zero to the end of the dosing interval
CL(ss)/F of AZD9291 After Multiple Dosing
Time frame: PK blood samples are collected multiple times on Cycle 1 Day 8 and Cycle 2 Day 1. Results are based on data cut off of 28 Jan 2016.
Pharmacokinetics of AZD9291 after multiple dosing by assessment of apparent plasma clearance at steady state
1 secondary outcome
Objective Response Rate (ORR)
Time frame: Treatment discontinuation plus 28 days or 12 months after last subject first dose (LSFD). Results are based on data cut off of 2 Nov 2016.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29239002Zhao H, Cao J, Chang J, Zhang Z, Yang L, Wang J, Cantarini M, Zhang L. Pharmacokinetics of Osimertinib in Chinese Patients With Advanced NSCLC: A Phase 1 Study. J Clin Pharmacol. 2018 Apr;58(4):504-513. doi: 10.1002/jcph.1042. Epub 2017 Dec 14.
- AURA18\_RedactedLink provided by the sponsor.
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Lung Adenocarcinoma, Stage III Lung Cancer
RecruitingPhase 1/2
Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)
High Grade Epithelial Ovarian Cancer, High Grade Serous Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD9291 40 mg and AZD9291 80 mg in people with Carcinoma, Non-Small-Cell Lung With EGFR Mutation Positive, run by AstraZeneca at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax of AZD9291 After Single Dosing (time frame: PK blood samples are collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post-dose. Results are based on data cut off of 28 Jan 2016.). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02529995, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2020.