Solid TumoursPhase 1NCT02923947
Study to Assess Osimertinib in Patients w/ Adv Solid Tumours & Normal Kidney Function or Severe Kidney Impairment
A Phase 1 study testing Osimertinib; AZD9291 in people with Solid Tumours, run by AstraZeneca at 11 sites in 3 countries.
Trial summary
The purpose of this study is to assess the effect of severe renal impairment on the levels of AZD9291 in the blood in patients with advanced solid tumours compared to patients with normal renal function Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Solid Tumours
- What is being tested?
- Osimertinib; AZD9291
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 4 May 2017to 28 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- For inclusion as a patient with severe renal impairment patient must have stable severe renal impairment (CrCl <30 mL/min at screening), for at least 2 months prior to the study.
- For inclusion as a patient with normal renal function, patient must have CrCl ≥90 mL/min at screening.
- >18 years old
- Histological or cytological confirmation of a solid, malignant tumour (excluding lymphoma) that is refractory to standard therapies or for which no standard therapies exist. Tumours in which inhibition of the EGFR pathway is considered relevant by the Investigator are not mandated but are encouraged.
- ECOG performance status ≤2
- Life expectancy of ≥12 weeks
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- BMI 18-35.
- Females should be using adequate contraceptive measures and must have a negative pregnancy test prior to dosing if of child-bearing potential or must have evidence of non-child bearing potential
- Males should use barrier contraception until 6 months after the last study drug is taken.
Who cannot join
- Participation in another clinical study with an IP during the last 14 days (or a longer period, depending on the agents used).
- Treatment with any of the following:
- Treatment with a 1st or 2nd generation EGFR-TKI within 8 days or approximately 5 half-lives, prior to the first dose of study drug.
- Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 14 days of the first dose of study drug.
- Osimertinib in the present study or has previously received a 3rd generation EGFR-TKI (eg, CO 1686).
- Major surgery within 4 weeks of the first dose of study drug.
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- Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment
- Currently receiving medications or herbal supplements known to be potent inducers of CYP3A4. Patients in Part B and continued access must avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known potent inducer effects on CYP3A4.
- Patients with severe renal impairment only: use of concurrent medication known to affect CrCl within 7 days of the first dose
- 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
- Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
- Absolute neutrophil count <1.5 x 109/L
- Platelet count <100 x 109/L
- Haemoglobin <90 g/L
- ALT >2.5 times the ULN if no demonstrable liver metastases or >5xULN in the presence of liver metastases
- AST >2.5xULN if no demonstrable liver metastases or > 5xULN in the presence of liver metastases
- Total bilirubin >1.5 times ULN if no liver metastases or >3xULN in the presence of liver metastases
- Any of the following cardiac criteria:
- Mean resting QT interval QTcF >470 msec, obtained from 3 ECGs.
- Abnormalities in rhythm, conduction or morphology of resting ECG
- 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
- Unable to swallow oral medication or patients with GI disorders or significant GI resection.
- Medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
- Severe portal hypertension or surgical porto-systemic shunts.
- Kidney transplant
- On dialysis
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
France5 sites
Research Site
Angers, 49055
Research Site
Bordeaux, 33000
Research Site
Dijon, 21079
Research Site
Lille, 59020
Research Site
Saint-Herblain, 44805
Spain4 sites
Research Site
Madrid, 28040
Research Site
Madrid, 28046
Research Site
Madrid, 28050
Research Site
Seville, 41013
About this study
Official title: Open-label,Non-randomised,Multicentre,Phase I Study to Assess the Pharmacokinetics, Safety & Tolerability of Osimertinib Following a Single Oral 80mg Dose to Patients w/ Adv Solid Tumours & Normal Renal Function or Severe Renal Impairment.
The purpose of this study is to assess the effect of severe renal impairment on the levels of AZD9291 in the blood in patients with advanced solid tumours compared to patients with normal renal function
Read the detailed description
This is a 3-part study (Part A, Part B and continued access) in patients with advanced solid tumours (excluding lymphoma) that are refractory to standard therapies or for which no standard therapies exist.
Part A will have a non-randomised, open-label, parallel group, multi-centre design to investigate the pharmacokinetics (PK) of a single dose of osimertinib in patients with severe renal impairment compared with patients with normal renal function. Patients with severe renal impairment will be recruited before those with normal renal function to allow the cohorts to be matched as closely as possible in terms of demographic characteristics (ie, age, body mass index [BMI] and sex).
Approximately 16 patients (8 with severe renal impairment and 8 with normal renal function) are planned to be enrolled to obtain at least 12 evaluable patients (6 with severe renal impairment and 6 with normal renal function) in Part A. A patient with severe renal impairment (as measured by the Cockcroft-Gault equation) is defined as having a creatinine clearance (CrCl) of <30 mL/min whilst a patient with normal renal function has a CrCl of ≥90 mL/min. Both the severe renal impairment and normal renal function patients will be recruited such that both groups will be matched for age, sex, and BMI to the maximum extent possible.
In Part A, each patient will receive a single oral dose of osimertinib 80 mg (given as a tablet). Where possible, patients will check into the clinic on Day -1, the evening prior to dosing (Day 1), and remain resident until 24 hours after the dose of osimertinib (Day 2) for collection of blood samples and 24-hour pooled urine for PK analysis during this time. Samples will be analysed to determine the concentrations of osimertinib and metabolites (AZ5104 and AZ7550) in plasma, urine, and plasma ultrafiltrate (PUF). Patients will then return to the clinic as outpatients for assessments on Day 3 (48 hours), Day 4 (72 hours), Day 6 (120 hours), Day 8 (168 hours) and Day 10 (216 hours).
Part B will allow patients with severe renal impairment, who complete Part A, to continue to receive osimertinib 80 mg once daily for 12 weeks and will provide additional safety data. Patients should start Part B after the last PK sample collected in Part A (ie, 216 hours after receiving the single dose of osimertinib in Part A).
If a patient does not immediately continue into Part B, this should be discussed on a case by case basis with the AstraZeneca physician or representative. Patients who enter Part B, will have weekly clinic visits for the first 3 weeks; thereafter visits will be every 3 weeks until Week 12. Safety assessments will be collected and there will be no formal evaluation of efficacy.
At the end of Part B, those patients with severe renal impairment who are deemed to be gaining clinical benefit from osimertinib will enter the continued access phase. Patients with normal renal function can enter the continued access phase immediately after completing Part A (ie, collection of the last PK sample scheduled on Day 10 of Part A). During the continued access phase, patients may continue to take osimertinib 80 mg once daily, if patients and the Investigator deem it appropriate, or until such time as their disease progresses, the Investigator believes the patients are no longer deriving clinical benefit, or patients stop taking osimertinib for any other reason. No clinical data, other than serious adverse events (SAEs) that may be related to the investigational product (IP), will be collected during this phase.
- Conditions
- Solid Tumours
- Being tested
- Osimertinib; AZD9291
- Keywords
- Pharmacokinetics,, Renal impairment,, Safety assessments,, Solid tumours,, EGFRm+, EGFRm+/T790M+ inhibitor
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Osimertinib; AZD9291Drug
Also called TAGRISSO™
80mg tablet dose to be taken orally - single dose in part A, daily dosing in Part B and continued access until progression or no longer receiving benefit
| Study group | Role | What they receive |
|---|---|---|
| Normal renal function | Experimental | For inclusion in the study as a patient with normal renal function, patients must have creatinine clearance ≥90 mL/min. Receives: Drug: Osimertinib; AZD9291 |
| Severe renal impairment | Experimental | For inclusion in the study as a patient with severe renal impairment, patients must have stable severe renal impairment (creatinine clearance <30 mL/min), as defined by the Cockcroft Gault equation, for at least 2 months prior to Day 1. Receives: Drug: Osimertinib; AZD9291 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration-time curve from zero to infinity for osimertinib
Part A: To investigate the PK of osimertinib after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs post-dose
Maximum plasma concentration for osimertinib
Part A: To investigate the PK of osimertinib after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs post-dose
Secondary outcomes (38)
Area under the plasma concentration-time curve from zero to the last quantifiable time point for osimertinib
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Area under the plasma concentration-time curve from zero to 24 hours post-dose for osimertinib
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24hrs for osimertinib post-dose
Time to maximum plasma concentration for osimertinib
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Apparent clearance following oral administration for osimertinib
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Apparent volume of distribution for osimertinib
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Terminal rate constant for osimertinib
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Terminal half-life for osimertinib
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Amount excreted in urine from time zero to 24 hours post-dose for osimertinib
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24hrs for osimertinib post-dose
Renal clearance for osimertinib
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24hrs post-dose for osimertinib plasma and 24 hour urine collection.
Maximum plasma concentration for AZ5104
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Maximum plasma concentration for AZ7550
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Time to maximum plasma concentration for AZ5104
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Time to maximum plasma concentration for AZ7550
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Area under the plasma concentration time curve from zero to infinity for AZ5104
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Area under the plasma concentration time curve from zero to infinity for AZ7550
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Area under the plasma concentration-time curve from zero to the last quantifiable time point for AZ5104
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Area under the plasma concentration-time curve from zero to the last quantifiable time point for AZ7550
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Amount excreted in urine from time zero to 24 hours post-dose for AZ5104
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: 24 hour pooled collection starting from time of dosing on Day 1
Amount excreted in urine from time zero to 24 hours post-dose for AZ7550
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: 24 hour pooled collection starting from time of dosing on Day 1
Terminal rate constant for AZ5104
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Terminal rate constant for AZ7550
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Terminal half-life for AZ5104
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Terminal half-life for AZ7550
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Renal clearance for AZ5104
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24hrs post-dose for AZ5104 plasma and 24 hour urine collection.
Renal clearance for AZ7550
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24 hours post-dose for AZ7550 plasma and 24 hour urine collection.
Metabolite to parent ratios for maximum plasma concentration
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Metabolite to parent ratios for area under the plasma concentration time curve from zero to infinity
Part A: To investigate the PK of osimertinib and metabolites (AZ5104 and AZ7550) after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Part A: Adverse Events's, graded by the National Cancer Institute Common Terminology Criteria for Adverse Event's (CTCAE v4.0)
Part A: To investigate the safety and tolerability of a single oral dose of osimertinib in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Part A: physical exam
Part A: To investigate the safety and tolerability of a single oral dose of osimertinib in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Part A: vital signs
Part A: To investigate the safety and tolerability of a single oral dose of osimertinib in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Part A: ECG
Part A: To investigate the safety and tolerability of a single oral dose of osimertinib in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Part A: evaluation of laboratory
Part A: To investigate the safety and tolerability of a single oral dose of osimertinib in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Part A: echocardiogram/MUGA.
Part A: To investigate the safety and tolerability of a single oral dose of osimertinib in patients with advanced solid tumours and normal renal function or severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Part B - Adverse events, graded CTCAE v4.0
Part B: To investigate the safety and tolerability of multiple oral doses of osimertinib in patients with advanced solid tumours and severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Part B -physical exam
Part B: To investigate the safety and tolerability of multiple oral doses of osimertinib in patients with advanced solid tumours and severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Part B - vital signs
Part B: To investigate the safety and tolerability of multiple oral doses of osimertinib in patients with advanced solid tumours and severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Part B - ECG
Part B: To investigate the safety and tolerability of multiple oral doses of osimertinib in patients with advanced solid tumours and severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Part B - evaluation of laboratory parameters.
Part B: To investigate the safety and tolerability of multiple oral doses of osimertinib in patients with advanced solid tumours and severe renal impairment.
Measured: Until 30 days following the final dose of osimertinib
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2016 (estimated)
- Study start4 May 2017
- Primary completion20 Sep 2018
- Study completion28 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumoursStudies 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Responsible party
- Sponsor
- Investigators
- Philippe Ravaud, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02923947
- Sponsor's protocol ID
- D5160C00035
- Status last verified
- Nov 2022
- First submitted
- 13 Sep 2016
- Last updated
- 27 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Publications
Vishwanathan K, Sanchez-Simon I, Keam B, Penel N, de Miguel-Luken M, Weilert D, Mills A, Marotti M, Johnson M, Ravaud A. A multicenter, phase I, pharmacokinetic study of osimertinib in cancer patients with normal renal function or severe renal impairment. Pharmacol Res Perspect. 2020 Aug;8(4):e00613. doi: 10.1002/prp2.613.
PubMed 32567817
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label,Non-randomised,Multicentre,Phase I Study to Assess the Pharmacokinetics, Safety & Tolerability of Osimertinib Following a Single Oral 80mg Dose to Patients w/ Adv Solid Tumours & Normal Renal Function or Severe Renal Impairment.
- ClinicalTrials.gov ID
- NCT02923947
- Acronym / sponsor ID
- D5160C00035
- Conditions
- Solid Tumours
- Keywords
- Pharmacokinetics,, Renal impairment,, Safety assessments,, Solid tumours,, EGFRm+, EGFRm+/T790M+ inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Study start
- 4 May 2017 (actual)
- Primary completion
- 20 Sep 2018 (actual)
- Study completion
- 28 Oct 2022 (actual)
- First posted
- 5 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the effect of severe renal impairment on the levels of AZD9291 in the blood in patients with advanced solid tumours compared to patients with normal renal function
Detailed description
This is a 3-part study (Part A, Part B and continued access) in patients with advanced solid tumours (excluding lymphoma) that are refractory to standard therapies or for which no standard therapies exist.
Part A will have a non-randomised, open-label, parallel group, multi-centre design to investigate the pharmacokinetics (PK) of a single dose of osimertinib in patients with severe renal impairment compared with patients with normal renal function. Patients with severe renal impairment will be recruited before those with normal renal function to allow the cohorts to be matched as closely as possible in terms of demographic characteristics (ie, age, body mass index [BMI] and sex).
Approximately 16 patients (8 with severe renal impairment and 8 with normal renal function) are planned to be enrolled to obtain at least 12 evaluable patients (6 with severe renal impairment and 6 with normal renal function) in Part A. A patient with severe renal impairment (as measured by the Cockcroft-Gault equation) is defined as having a creatinine clearance (CrCl) of <30 mL/min whilst a patient with normal renal function has a CrCl of ≥90 mL/min. Both the severe renal impairment and normal renal function patients will be recruited such that both groups will be matched for age, sex, and BMI to the maximum extent possible.
In Part A, each patient will receive a single oral dose of osimertinib 80 mg (given as a tablet). Where possible, patients will check into the clinic on Day -1, the evening prior to dosing (Day 1), and remain resident until 24 hours after the dose of osimertinib (Day 2) for collection of blood samples and 24-hour pooled urine for PK analysis during this time. Samples will be analysed to determine the concentrations of osimertinib and metabolites (AZ5104 and AZ7550) in plasma, urine, and plasma ultrafiltrate (PUF). Patients will then return to the clinic as outpatients for assessments on Day 3 (48 hours), Day 4 (72 hours), Day 6 (120 hours), Day 8 (168 hours) and Day 10 (216 hours).
Part B will allow patients with severe renal impairment, who complete Part A, to continue to receive osimertinib 80 mg once daily for 12 weeks and will provide additional safety data. Patients should start Part B after the last PK sample collected in Part A (ie, 216 hours after receiving the single dose of osimertinib in Part A).
If a patient does not immediately continue into Part B, this should be discussed on a case by case basis with the AstraZeneca physician or representative. Patients who enter Part B, will have weekly clinic visits for the first 3 weeks; thereafter visits will be every 3 weeks until Week 12. Safety assessments will be collected and there will be no formal evaluation of efficacy.
At the end of Part B, those patients with severe renal impairment who are deemed to be gaining clinical benefit from osimertinib will enter the continued access phase. Patients with normal renal function can enter the continued access phase immediately after completing Part A (ie, collection of the last PK sample scheduled on Day 10 of Part A). During the continued access phase, patients may continue to take osimertinib 80 mg once daily, if patients and the Investigator deem it appropriate, or until such time as their disease progresses, the Investigator believes the patients are no longer deriving clinical benefit, or patients stop taking osimertinib for any other reason. No clinical data, other than serious adverse events (SAEs) that may be related to the investigational product (IP), will be collected during this phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal renal function | Experimental | Drug: Osimertinib; AZD9291For inclusion in the study as a patient with normal renal function, patients must have creatinine clearance ≥90 mL/min. |
| Severe renal impairment | Experimental | Drug: Osimertinib; AZD9291For inclusion in the study as a patient with severe renal impairment, patients must have stable severe renal impairment (creatinine clearance <30 mL/min), as defined by the Cockcroft Gault equation, for at least 2 months prior to Day 1. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- For inclusion as a patient with severe renal impairment patient must have stable severe renal impairment (CrCl <30 mL/min at screening), for at least 2 months prior to the study.
- For inclusion as a patient with normal renal function, patient must have CrCl ≥90 mL/min at screening.
- >18 years old
- Histological or cytological confirmation of a solid, malignant tumour (excluding lymphoma) that is refractory to standard therapies or for which no standard therapies exist. Tumours in which inhibition of the EGFR pathway is considered relevant by the Investigator are not mandated but are encouraged.
- ECOG performance status ≤2
Key exclusion criteria (27 listed)
- Participation in another clinical study with an IP during the last 14 days (or a longer period, depending on the agents used).
- Treatment with any of the following:
- Patients with severe renal impairment only: use of concurrent medication known to affect CrCl within 7 days of the first dose
- 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
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 |
|---|---|---|
| Osimertinib; AZD9291Also: TAGRISSO™80mg tablet dose to be taken orally - single dose in part A, daily dosing in Part B and continued access until progression or no longer receiving benefit | Drug | Normal renal function, Severe renal impairment |
Primary outcome
Area under the plasma concentration-time curve from zero to infinity for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs post-dose
Part A: To investigate the PK of osimertinib after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
Maximum plasma concentration for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs post-dose
Part A: To investigate the PK of osimertinib after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.
38 secondary outcomes
Area under the plasma concentration-time curve from zero to the last quantifiable time point for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Area under the plasma concentration-time curve from zero to 24 hours post-dose for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24hrs for osimertinib post-dose
Time to maximum plasma concentration for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Apparent clearance following oral administration for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Apparent volume of distribution for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Terminal rate constant for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Terminal half-life for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Amount excreted in urine from time zero to 24 hours post-dose for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24hrs for osimertinib post-dose
Renal clearance for osimertinib
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24hrs post-dose for osimertinib plasma and 24 hour urine collection.
Maximum plasma concentration for AZ5104
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Maximum plasma concentration for AZ7550
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Time to maximum plasma concentration for AZ5104
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Time to maximum plasma concentration for AZ7550
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Area under the plasma concentration time curve from zero to infinity for AZ5104
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Area under the plasma concentration time curve from zero to infinity for AZ7550
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Area under the plasma concentration-time curve from zero to the last quantifiable time point for AZ5104
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Area under the plasma concentration-time curve from zero to the last quantifiable time point for AZ7550
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Amount excreted in urine from time zero to 24 hours post-dose for AZ5104
Time frame: 24 hour pooled collection starting from time of dosing on Day 1
Amount excreted in urine from time zero to 24 hours post-dose for AZ7550
Time frame: 24 hour pooled collection starting from time of dosing on Day 1
Terminal rate constant for AZ5104
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Terminal rate constant for AZ7550
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Terminal half-life for AZ5104
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Terminal half-life for AZ7550
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Renal clearance for AZ5104
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24hrs post-dose for AZ5104 plasma and 24 hour urine collection.
Renal clearance for AZ7550
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24 hours post-dose for AZ7550 plasma and 24 hour urine collection.
Metabolite to parent ratios for maximum plasma concentration
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Metabolite to parent ratios for area under the plasma concentration time curve from zero to infinity
Time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose
Part A: Adverse Events's, graded by the National Cancer Institute Common Terminology Criteria for Adverse Event's (CTCAE v4.0)
Time frame: Until 30 days following the final dose of osimertinib
Part A: physical exam
Time frame: Until 30 days following the final dose of osimertinib
Part A: vital signs
Time frame: Until 30 days following the final dose of osimertinib
Part A: ECG
Time frame: Until 30 days following the final dose of osimertinib
Part A: evaluation of laboratory
Time frame: Until 30 days following the final dose of osimertinib
Part A: echocardiogram/MUGA.
Time frame: Until 30 days following the final dose of osimertinib
Part B - Adverse events, graded CTCAE v4.0
Time frame: Until 30 days following the final dose of osimertinib
Part B -physical exam
Time frame: Until 30 days following the final dose of osimertinib
Part B - vital signs
Time frame: Until 30 days following the final dose of osimertinib
Part B - ECG
Time frame: Until 30 days following the final dose of osimertinib
Part B - evaluation of laboratory parameters.
Time frame: Until 30 days following the final dose of osimertinib
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2023.
- Derived from this study: PubMed 32567817Vishwanathan K, Sanchez-Simon I, Keam B, Penel N, de Miguel-Luken M, Weilert D, Mills A, Marotti M, Johnson M, Ravaud A. A multicenter, phase I, pharmacokinetic study of osimertinib in cancer patients with normal renal function or severe renal impairment. Pharmacol Res Perspect. 2020 Aug;8(4):e00613. doi: 10.1002/prp2.613.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
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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.
Philippe Ravaud, MD principal investigator
Columbia University
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Osimertinib; AZD9291 in people with Solid Tumours, run by AstraZeneca at 11 sites in 3 countries.
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 9 inclusion and 27 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 27 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France, Spain, South Korea. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Area under the plasma concentration-time curve from zero to infinity for osimertinib (time frame: On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs post-dose). The study lists 2 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 NCT02923947, 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 27 Nov 2023.