Solid MalignanciesPhase 114CNCT02640755

Absorption, Metabolism, Excretion and Pharmacokinetics of a Single Dose [14C]AZD2014 Followed by a Multiple Dose Phase

A Phase 1 study testing [14C]AZD2014, Multiple dose AZD2014 and Fulvestrant in people with Solid Malignancies, run by AstraZeneca at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This Phase 1, open label, single centre, non-randomised study in patients with advanced solid malignancies consists of two parts: 1. Single Dose Period - will characterise the absorption, metabolism, excretion and pharmacokinetics of a single oral dose of [14C]AZD2014 from the body 2. Read more about this study

Who is it for?: Ages 18 to 130 years
Conditions the study is for: Solid Malignancies
What is being tested?: [14C]AZD2014, Multiple dose AZD2014 and Fulvestrant
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4 participants
Where: 1 siteUnited Kingdom
Study dates: 28 Jan 2016to 6 Jul 2017
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 of signed, written \& dated informed consent prior to any study specific procedures.
Male or female patients aged at least 18 years.
Have a body mass index (BMI) ≥18 kg/m2 and ≤35 kg/m2 \& weigh at least 50 kg.
Histological or cytological confirmation of a solid malignant tumour that is refractory or resistant to standard therapies or for which no suitable effective standard therapies exist. SqNSCLC patients are excluded from the 50mg BD AZD2014 in combination with paclitaxel cohort.
For patients intending to enter combination therapy with fulvestrant or paclitaxel, this should be deemed as an appropriate treatment option by Investigator.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 with no deterioration over previous 2 weeks \& minimum life expectancy of 12 weeks.

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At least one lesion (measurable and/or non-measurable but evaluable) that can be accurately assessed at baseline by computerised tomography (CT) magnetic resonance imaging (MRI) or plain X-ray \& is suitable for repeated assessment
Able \& willing to stay in hospital for approximately 9 days
Females should be using adequate contraceptive measures, should not be breast feeding \& must have negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential
Male patients should be surgically sterile or willing to use barrier contraception ie, condoms and spermicide \&refrain from donating sperm from start of dosing until 16 weeks after discontinuing of study treatment.
Regular bowel movements (ie, on average production of at least 1 stool per day)

Who cannot join

Involvement in planning and/or conduct of the study
Previous enrolment in present study
Another study with an investigational product in last 28 days
Chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents \& any investigational agents within 21 days of starting treatment (not including palliative radiotherapy at focal sites), or corticosteroids within 14 days
Major surgery within 4 weeks, or minor surgery within 14 days
Exposure to strong and moderate inhibitors or inducers of cytochrome P450 (CYP) 3A4/5, P-glycoprotein (Pgp) (multidrug resistance gene [MDR1]), and breast cancer resistance protein (BCRP), if taken within stated washout periods

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Exposure to specific substrates of the drug organic anion-transporting polypeptide (OATP)1B1, OATP1B3, organic anion transporting polypeptide (OCT)1 and OCT2 within appropriate washout period
Any haemopoietic growth factors (eg, filgrastim [granulocyte colony-stimulating factor; G-CSF], sargramostim [granulocyte-macrophage colony-stimulating factor; GM-CSF]) within 14 days prior to receiving study treatment
Previous treatment with AZD2014 or AZD8055
Patients who have received fulvestrant within 3 months
With exception of alopecia, any unresolved toxicities chemotherapy/radiotherapy should be no greater than CTCAE grade 1
Participated in another absorption, distribution, metabolism and excretion study within 1 year
Spinal cord compression and/or brain metastases unless asymptomatic or treated \& stable off steroids for at least 4 weeks
Severe or uncontrolled systemic diseases (eg, severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]), or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension, active bleeding diatheses or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
Recent history of drug abuse or alcohol abuse
Patients who have undergone any of the following procedures or experienced conditions currently or in preceding 12 months:
Coronary artery bypass graft
Angioplasty
Vascular stent
Myocardial infarction
Angina pectoris
Congestive heart failure New York Heart Association Grade 2
Ventricular arrhythmias requiring continuous therapy
Uncontrolled supraventricular arrhythmias including atrial fibrillation
Haemorrhagic or thrombotic stroke, including transient ischaemic attacks or other central nervous system bleeding
Abnormal echocardiogram at baseline (left ventricular ejection fraction [LVEF] <55% and shortening fraction [SF] <15%)
Torsades de Pointes either currently or within 12 months
Mean resting QTcF ≥470 ms
Medications known to prolong QT interval, or that increase the risk of QTc prolongation or arrhythmic events (such as heart failure, hypokalaemia, congenital long QT syndrome, family history of either long QT syndrome), or unexplained sudden death under 40 years of age
Laboratory values as listed below:
Absolute neutrophil count <1.5x109/L
Platelet count <100x109/L
Haemoglobin <90 g/L
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or >5xULN in the presence of liver metastases
Total bilirubin >1.5xULN if no demonstrable liver metastases or >3xULN in the presence of liver metastases
Serum creatinine >1.5xULN concurrent with creatinine clearance <50 mL/min (measured or calculated by Cockcroft and Gault equation), confirmation of creatinine clearance is only required when creatinine is >1.5xULN
Clinically relevant and treatment resistant abnormalities in potassium, sodium, calcium (corrected for plasma albumin) or magnesium
Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis
Abnormal fasting glucose >126 mg/dL (>7 mmol/L)
Patients with diabetes Type 1 or uncontrolled Type 2 (glycosylated haemoglobin [HbA1c] >8% [64 mmol/mol] assessed locally)
Current refractory nausea and vomiting, chronic gastrointestinal disease or inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption
History of hypersensitivity to active or inactive excipients of AZD2014 or drugs with a similar chemical structure or class to AZD2014
Judgment that patient is unsuitable to participate in study and unlikely to comply with study procedures, restrictions \& requirements

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Research Site
Manchester, M20 4BX

Other trials in United Kingdom

About this study

Official title: A Phase I, Open-Label, Non-randomised, Single Centre Study of the Absorption, Metabolism, Excretion and Pharmacokinetics of AZD2014 After a Single Oral Dose of [14C]AZD2014, Followed by Multiple Doses of AZD2014 Either As Monotherapy or In Combination With Either Fulvestrant or Paclitaxel in Patients With Advanced Solid Malignancies

This Phase 1, open label, single centre, non-randomised study in patients with advanced solid malignancies consists of two parts:

Single Dose Period - will characterise the absorption, metabolism, excretion and pharmacokinetics of a single oral dose of [14C]AZD2014 from the body
Multiple Dose Period - will further assess the safety and tolerability and anti-tumour activity of multiple doses of AZD2014 when given as a monotherapy or given in combination with paclitaxel or fulvestrant.

Read the detailed description

This is a Phase I, open label, single centre, non-randomised study in patients with advanced solid malignancies that is refractory or resistant to standard treatment or where no suitable effective standard treatment exists or for whom paclitaxel or fulvestrant are appropriate treatment choices. The study will be divided in two parts:

Single Dose Period - will enrol up to 6 evaluable patients to characterise the absorption, metabolism, excretion and pharmacokinetics of a single radiolabelled [14C] oral dose of 125mg AZD2014 via residential intensive PK sampling over 8 days. An evaluable patient is defined as patient who does not vomit within 2 hours post dose and who has completed the scheduled PK sampling.
Multiple Dose Period - patients who have completed the Single Dose Period may continue to receive treatment as outpatients. Patients will be allocated to different treatment regimes as decided between Investigator and patient on a risk / benefit basis. From Day 1, Cycle 1, non-radiolabelled AZD2014 treatment will be administered as oral tablets to patients, either as:
50mg BD monotherapy ii. 125mg BD taken on first 2 days of treatment each week in combination with 500mg intramuscular fulvestrant on Day 1, Cycle 1, Day 15, Cycle 1; Day 1, Cycle 2, then Day 1 of each monthly cycle thereafter iii. 50mg BD taken on first 3 days of treatment each week for 6 weeks in combination with a single weekly paclitaxel infusion (80mg/m2 ) followed by a one week break from treatment where no AZD2014 or paclitaxel will be given. This 7 week schedule composes one cycle of treatment. Patients will be given up to 6 cycles of paclitaxel, although additional cycles of paclitaxel may be given if deemed appropriate by the Investigator.

Radiolabelled AZD2014 will be administered to fasted patients (i.e. no food 2 hours before and 1 hour after each dose). Non-radiolabelled AZD2014 will be administered either under fasted or non-fasted conditions. The safety and tolerability and anti-tumour activity of AZD2014 and combination with paclitaxel or fulvestrant will be evaluated in all enrolled patients respectively using conventional safety parameters, AEs/SAEs and RECIST 1.1.

Conditions: Solid Malignancies
Being tested: [14C]AZD2014, Multiple dose AZD2014, Fulvestrant, Paclitaxel
Keywords: Radiolabelled

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

[14C]AZD2014Drug
Radiolabelled dual TORC1/TORC2 inhibitor
Multiple dose AZD2014Drug
Dual TORC1/TORC2 inhibitor
FulvestrantDrug
Hormonal Agent
PaclitaxelDrug
Taxane

Study groups in NCT02640755
Study group	Role	What they receive
[14C]AZD2014 followed by AZD2014 Monotherapy	Experimental	Arm will be comprised of [14C]AZD2014 followed by AZD2014 Monotherapy Receives: Drug: [14C]AZD2014; Drug: Multiple dose AZD2014
[14C]AZD2014 followed by AZD2014 + Fulvestrant	Experimental	Arm will be comprised of [14C]AZD2014 followed by AZD2014 + Fulvestrant Receives: Drug: [14C]AZD2014; Drug: Multiple dose AZD2014; Drug: Fulvestrant
[14C]AZD2014 followed by AZD2014 + Paclitaxel	Experimental	Arm will be comprised of [14C]AZD2014 followed by AZD2014 + Paclitaxel Receives: Drug: [14C]AZD2014; Drug: Multiple dose AZD2014; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
The mean concentrations of total radioactivity in plasma collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 48 hours post-dose. Geometric mean concentrations were not quantifiable after 48 hours. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32 and 48 hours (h) post [14C]-AZD2014 dose in the Single Dose Period.
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
The mean concentrations of AZD2014 in plasma collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 24 hours post-dose. Geometric mean concentrations were not quantifiable after 24 hours.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014
The mean concentrations of total radioactivity in saliva collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of saliva collection up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total [14C] radioactivity in saliva was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
Measured: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.
AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014
The mean concentrations of AZD2014 in saliva collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours.
Measured: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
The mean concentrations of total radioactivity in blood collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of blood sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.
Cumulative Percentage of [14C]-AZD2014 Recovered by Day 8
The mean cumulative percentage of [14C]-AZD2014 dose recovered as total radioactivity by the end of the Single Dose Period (Day 1 - 8) is presented. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Measured: From pre-dose Day 1 to Day 8 of the Single Dose Period.
Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva
Mean AZD2014 Cmax values in plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva
AZD2014 Tmax values for plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva
AZD2014 t(last) values in plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Area Under the Plasma Concentration-time Curve (AUC) for AZD2014
Mean AUC for AZD2014 following administration of [14C]-AZD2014 on Day 1 is presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva
Mean AUC(0-t) values in plasma and saliva for AZD2014 following administration of [14C]-AZD2014 on Day 1 are presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Apparent Total Body Clearance (CL/F) of AZD2014
The mean CL/F of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
Mean Residence Time (MRT) of AZD2014
The MRT of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
Apparent Volume of Distribution at Steady State (Vss/F) for AZD2014 in Plasma
The mean Vss/F of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
Terminal Elimination Rate Constant (lambda_z) for AZD2014 in Plasma
The mean lambda_z of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
Half-life Associated With Terminal Slope (lambda_z) of a Semi-logarithmic Concentration-time Curve (t1/2[lambda_z]) for AZD2014 in Plasma
The mean t1/2(lambda_z) for AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h ost [14C]-AZD2014 dose in the Single Dose Period.
Cmax for Total [14C] Radioactivity in Whole Blood and Saliva
Mean [14C] radioactivity Cmax values in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 are presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Tmax for [14C] Radioactivity in Whole Blood and Saliva
[14C] radioactivity tmax in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 is presented .
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
T(Last) for [14C] Radioactivity in Whole Blood and Saliva
Mean [14C] radioactivity t(last) values in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 are presented.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
The mean ratios of whole blood total radioactivity to plasma total radioactivity are presented for the timepoints of sample collection up to 12 hours post-dose. Geometric mean ratios were not calculated after 12 hours.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose.
Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva
The mean ratios of saliva AZD2014 to saliva radioactivity concentrations are presented for the timepoints of saliva collection up to 10 hours post-dose. Geometric mean ratios were not calculated after 10 hours. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Measured: Saliva was collected at 1, 2, 4, 6, 8 and 10 h post [14C]-AZD2014 dose in the Single Dose Period.
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
Mean fe%(R) values per urine collection period are presented as a percentage of the total [14C]-AZD2014 dose administered on Day 1.
Measured: Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.
Renal Clearance (CL[R]) of AZD2014 From Plasma.
CL(R) of AZD2014 from plasma up to 168 h post-dose.
Measured: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
fe cum%(R) by the end of each collection period is presented following administration of [14C]-AZD2014.
Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Measured: Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.
Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])
fe cum%(f) by the end of each collection period is presented following administration of [14C]-AZD2014.
Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Measured: Stool was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.

Secondary outcomes (3)

Number of AEs Experienced by Patients.
AEs (including serious AEs [SAEs]) were collected from the time of informed consent (Visit 1) and throughout the study, including the 30-day follow-up. The numbers of patients experiencing any AEs and SAEs, causally related AEs and SAEs, and SAEs which were fatal are presented.
Measured: From Day 1 of the Single Dose Period to 30 days after the last dose of AZD2014 administered in the Multiple Dose Period.
Best Overall Response (BOR) Assessment
Anti-tumour activity through assessment of BOR. BOR was defined for each patient as follows according to the RECIST 1.1 criteria:
Complete Response (CR): Disappearance of all target lesions since baseline. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions.
Stable Disease (SD): Any cases that do not qualify for either PR or progressive disease (PD).
PD: At least a 20% increase in the sum of the diameters of target lesions. BOR for each patient was determined as the best response recorded from the day study treatment started until progression or until the last evaluable RECIST tumour assessment in the absence of progression.
Measured: RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.
Best Percentage Change in Tumour Size From Baseline
Assessment of anti-tumour activity through measurement of tumour lesions. Tumour size was defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions.
Measured: RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jan 20166 Jul 2017

First posted29 Dec 2015 (estimated)
Study start28 Jan 2016
Primary completion21 Dec 2016
Study completion6 Jul 2017

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.
Other trials for Solid MalignanciesStudies 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: 4 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02640755
Sponsor's protocol ID: D2270C00015
Other IDs: 2015-000198-11, 2015
Acronym: 14C
Status last verified: Jan 2019
First submitted: 14 Dec 2015
Last updated: 22 Apr 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 22 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open-Label, Non-randomised, Single Centre Study of the Absorption, Metabolism, Excretion and Pharmacokinetics of AZD2014 After a Single Oral Dose of [14C]AZD2014, Followed by Multiple Doses of AZD2014 Either As Monotherapy or In Combination With Either Fulvestrant or Paclitaxel in Patients With Advanced Solid Malignancies
ClinicalTrials.gov ID: NCT02640755
Acronym / sponsor ID: 14C / D2270C00015
Conditions: Solid Malignancies
Keywords: Radiolabelled
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 4 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Quintiles, Inc.
Study start: 28 Jan 2016 (actual)
Primary completion: 21 Dec 2016 (actual)
Study completion: 6 Jul 2017 (actual)
First posted: 29 Dec 2015 (estimated)
Results: Posted 22 Apr 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This Phase 1, open label, single centre, non-randomised study in patients with advanced solid malignancies consists of two parts:

Single Dose Period - will characterise the absorption, metabolism, excretion and pharmacokinetics of a single oral dose of [14C]AZD2014 from the body
Multiple Dose Period - will further assess the safety and tolerability and anti-tumour activity of multiple doses of AZD2014 when given as a monotherapy or given in combination with paclitaxel or fulvestrant.

Detailed description

Single Dose Period - will enrol up to 6 evaluable patients to characterise the absorption, metabolism, excretion and pharmacokinetics of a single radiolabelled [14C] oral dose of 125mg AZD2014 via residential intensive PK sampling over 8 days. An evaluable patient is defined as patient who does not vomit within 2 hours post dose and who has completed the scheduled PK sampling.
Multiple Dose Period - patients who have completed the Single Dose Period may continue to receive treatment as outpatients. Patients will be allocated to different treatment regimes as decided between Investigator and patient on a risk / benefit basis. From Day 1, Cycle 1, non-radiolabelled AZD2014 treatment will be administered as oral tablets to patients, either as:
50mg BD monotherapy ii. 125mg BD taken on first 2 days of treatment each week in combination with 500mg intramuscular fulvestrant on Day 1, Cycle 1, Day 15, Cycle 1; Day 1, Cycle 2, then Day 1 of each monthly cycle thereafter iii. 50mg BD taken on first 3 days of treatment each week for 6 weeks in combination with a single weekly paclitaxel infusion (80mg/m2 ) followed by a one week break from treatment where no AZD2014 or paclitaxel will be given. This 7 week schedule composes one cycle of treatment. Patients will be given up to 6 cycles of paclitaxel, although additional cycles of paclitaxel may be given if deemed appropriate by the Investigator.

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
[14C]AZD2014 followed by AZD2014 Monotherapy	Experimental	Drug: [14C]AZD2014, Drug: Multiple dose AZD2014Arm will be comprised of [14C]AZD2014 followed by AZD2014 Monotherapy
[14C]AZD2014 followed by AZD2014 + Fulvestrant	Experimental	Drug: [14C]AZD2014, Drug: Multiple dose AZD2014, Drug: FulvestrantArm will be comprised of [14C]AZD2014 followed by AZD2014 + Fulvestrant
[14C]AZD2014 followed by AZD2014 + Paclitaxel	Experimental	Drug: [14C]AZD2014, Drug: Multiple dose AZD2014, Drug: PaclitaxelArm will be comprised of [14C]AZD2014 followed by AZD2014 + Paclitaxel

Who may qualify

Ages: 18 to 130 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Provision of signed, written \& dated informed consent prior to any study specific procedures.
Male or female patients aged at least 18 years.
Have a body mass index (BMI) ≥18 kg/m2 and ≤35 kg/m2 \& weigh at least 50 kg.
Histological or cytological confirmation of a solid malignant tumour that is refractory or resistant to standard therapies or for which no suitable effective standard therapies exist. SqNSCLC patients are excluded from the 50mg BD AZD2014 in combination with paclitaxel cohort.
For patients intending to enter combination therapy with fulvestrant or paclitaxel, this should be deemed as an appropriate treatment option by Investigator.

Key exclusion criteria (43 listed)

Involvement in planning and/or conduct of the study
Previous enrolment in present study
Another study with an investigational product in last 28 days
Chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents \& any investigational agents within 21 days of starting treatment (not including palliative radiotherapy at focal sites), or corticosteroids within 14 days
Major surgery within 4 weeks, or minor surgery within 14 days

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
[14C]AZD2014Radiolabelled dual TORC1/TORC2 inhibitor	Drug	[14C]AZD2014 followed by AZD2014 + Fulvestrant, [14C]AZD2014 followed by AZD2014 + Paclitaxel, [14C]AZD2014 followed by AZD2014 Monotherapy
Multiple dose AZD2014Dual TORC1/TORC2 inhibitor	Drug	[14C]AZD2014 followed by AZD2014 + Fulvestrant, [14C]AZD2014 followed by AZD2014 + Paclitaxel, [14C]AZD2014 followed by AZD2014 Monotherapy
FulvestrantHormonal Agent	Drug	[14C]AZD2014 followed by AZD2014 + Fulvestrant
PaclitaxelTaxane	Drug	[14C]AZD2014 followed by AZD2014 + Paclitaxel

Primary outcome

Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32 and 48 hours (h) post [14C]-AZD2014 dose in the Single Dose Period.
The mean concentrations of total radioactivity in plasma collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 48 hours post-dose. Geometric mean concentrations were not quantifiable after 48 hours. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
The mean concentrations of AZD2014 in plasma collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 24 hours post-dose. Geometric mean concentrations were not quantifiable after 24 hours.
Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014
Time frame: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.
The mean concentrations of total radioactivity in saliva collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of saliva collection up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total [14C] radioactivity in saliva was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014
Time frame: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.
The mean concentrations of AZD2014 in saliva collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours.
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.
The mean concentrations of total radioactivity in blood collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of blood sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
Cumulative Percentage of [14C]-AZD2014 Recovered by Day 8
Time frame: From pre-dose Day 1 to Day 8 of the Single Dose Period.
The mean cumulative percentage of [14C]-AZD2014 dose recovered as total radioactivity by the end of the Single Dose Period (Day 1 - 8) is presented. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Mean AZD2014 Cmax values in plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented.
Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
AZD2014 Tmax values for plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented.
Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
AZD2014 t(last) values in plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented.
Area Under the Plasma Concentration-time Curve (AUC) for AZD2014
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
Mean AUC for AZD2014 following administration of [14C]-AZD2014 on Day 1 is presented.
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Mean AUC(0-t) values in plasma and saliva for AZD2014 following administration of [14C]-AZD2014 on Day 1 are presented.
Apparent Total Body Clearance (CL/F) of AZD2014
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
The mean CL/F of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented.
Mean Residence Time (MRT) of AZD2014
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
The MRT of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented.
Apparent Volume of Distribution at Steady State (Vss/F) for AZD2014 in Plasma
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
The mean Vss/F of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented.
Terminal Elimination Rate Constant (lambda_z) for AZD2014 in Plasma
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
The mean lambda_z of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented.
Half-life Associated With Terminal Slope (lambda_z) of a Semi-logarithmic Concentration-time Curve (t1/2[lambda_z]) for AZD2014 in Plasma
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h ost [14C]-AZD2014 dose in the Single Dose Period.
The mean t1/2(lambda_z) for AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented.
Cmax for Total [14C] Radioactivity in Whole Blood and Saliva
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Mean [14C] radioactivity Cmax values in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 are presented.
Tmax for [14C] Radioactivity in Whole Blood and Saliva
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
[14C] radioactivity tmax in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 is presented .
T(Last) for [14C] Radioactivity in Whole Blood and Saliva
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.
Mean [14C] radioactivity t(last) values in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 are presented.
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose.
The mean ratios of whole blood total radioactivity to plasma total radioactivity are presented for the timepoints of sample collection up to 12 hours post-dose. Geometric mean ratios were not calculated after 12 hours.
Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva
Time frame: Saliva was collected at 1, 2, 4, 6, 8 and 10 h post [14C]-AZD2014 dose in the Single Dose Period.
The mean ratios of saliva AZD2014 to saliva radioactivity concentrations are presented for the timepoints of saliva collection up to 10 hours post-dose. Geometric mean ratios were not calculated after 10 hours. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
Time frame: Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.
Mean fe%(R) values per urine collection period are presented as a percentage of the total [14C]-AZD2014 dose administered on Day 1.
Renal Clearance (CL[R]) of AZD2014 From Plasma.
Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
CL(R) of AZD2014 from plasma up to 168 h post-dose.
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
Time frame: Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.
fe cum%(R) by the end of each collection period is presented following administration of [14C]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])
Time frame: Stool was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.
fe cum%(f) by the end of each collection period is presented following administration of [14C]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.

3 secondary outcomes

Number of AEs Experienced by Patients.
Time frame: From Day 1 of the Single Dose Period to 30 days after the last dose of AZD2014 administered in the Multiple Dose Period.
Best Overall Response (BOR) Assessment
Time frame: RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.
Best Percentage Change in Tumour Size From Baseline
Time frame: RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.

Results and safety

Results posted to the registry on 22 Apr 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
[14C]-AZD2014 Then AZD2014 Monotherapy	3	3
[14C]-AZD2014 Then AZD2014 + Fulvestrant	1	1

Primary outcome: Total Radioactivity in Plasma Following Administration of [14C]-AZD2014

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32 and 48 hours (h) post [14C]-AZD2014 dose in the Single Dose Period.. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram equivalent/millilitre (ngEq/mL)

Measure	[14C]-AZD2014 (Period 1 [Day 1 - 8]) n = 4
0.5 h (n = 3)	4013 (41.55)
1 h (n = 4)	3415 (40.69)
1.5 h (n = 4)	2901 (34.87)
2 h (n = 4)	2693 (36.75)
3 h (n = 4)	2105 (38.82)
4 h (n = 4)	1818 (37.85)
6 h (n = 4)	1419 (37.31)
8 h (n = 4)	914.1 (42.85)

Population analysed: The Pharmacokinetic (PK) analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.

Primary outcome: AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	[14C]-AZD2014 (Period 1 [Day 1 - 8]) n = 4
0.5 h (n = 3)	3704 (29.79)
1 h (n = 4)	3090 (39.49)
1.5 h (n = 4)	2758 (26.33)
2 h (n = 4)	2409 (22.11)
3 h (n = 4)	1768 (26.45)
4 h (n = 4)	1439 (43.74)
6 h (n = 4)	917.7 (8.278)
8 h (n = 4)	619.4 (40.08)

Population analysed: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.

Primary outcome: Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014

Time frame: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.. Geometric mean (Geometric Coefficient of Variation). Unit: ngEq/mL

Measure	[14C]-AZD2014 (Period 1 [Day 1 - 8]) n = 4
1 h (n = 2)	5495 (89.69)
2 h (n = 3)	650.2 (52.98)
4 h (n = 3)	264.3 (62.10)
6 h (n = 3)	135.4 (73.87)
8 h (n = 3)	158.5 (33.15)
10 h (n = 3)	105.2 (39.57)
12 h (n = 3)	104.0 (48.01)

Primary outcome: AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014

Time frame: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	[14C]-AZD2014 (Period 1 [Day 1 - 8]) n = 4
1 h (n = 3)	4159 (84.68)
2 h (n = 4)	416.3 (84.85)
4 h (n = 4)	169.1 (52.50)
6 h (n = 4)	75.08 (40.23)
8 h (n = 4)	73.27 (15.19)
10 h (n = 3)	32.59 (60.47)
12 h (n = 2)	33.96 (69.25)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
[14C]-AZD2014 Then AZD2014 Monotherapy	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
[14C]-AZD2014 Then AZD2014 + Fulvestrant	1 of 1 (100%)	1 of 1 (100%)	Not reported

Limitations and caveats (from the sponsor): No patients were recruited into AZD2014 + paclitaxel treatment regimen, as per the protocol plan.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Emma Dean, MD principal investigator

The Christie NHS Foundation Trust

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing [14C]AZD2014, Multiple dose AZD2014 and Fulvestrant in people with Solid Malignancies, run by AstraZeneca at 1 site in United Kingdom.

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 11 inclusion and 43 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 22 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. 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 22 Apr 2019). 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?

Total Radioactivity in Plasma Following Administration of [14C]-AZD2014 (time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32 and 48 hours (h) post [14C]-AZD2014 dose in the Single Dose Period.). The study lists 25 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 NCT02640755.

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 22 Apr 2019.