Advanced Solid MalignanciesPhase 1NCT01026402
Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of AZD2014
A Phase 1 study testing AZD2014 in people with Advanced Solid Malignancies, run by AstraZeneca at 2 sites in United Kingdom.
Trial summary
The main purpose of the study is to establish a safe dose of the drug by providing information on any potential side effects this drug may cause and collecting data about how a patient's cancer responds to the drug. Read more about this study
- Who is it for?
- Ages 18 to 150 years
- Conditions the study is for
- Advanced Solid Malignancies
- What is being tested?
- AZD2014
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Dec 2009to Aug 2014
- 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 150 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological or cytological confirmation of a solid, malignant tumour that is refractory to standard therapies or for which no standard therapies exist
- At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computerised tomography (CT) magnetic resonance imaging (MRI) or plain X-ray and is suitable for repeated assessment
- World Health Organisation performance status 0-2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
Who cannot join
- Patients with severe laboratory abnormalities for haematology, liver or renal function. Also treatment with any haemopoietic growth factors are not allowed within two weeks prior to first dose of study drug
- Patients with abnormal fasting glucose, type I or uncontrolled type II diabetes
- Patients with severe cardiac condition of ischemia, impaired ventricular function and arrhythmias, evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the mTor Kinase Inhibitor AZD2014 Administered Orally to Patients With Advanced Solid Malignancies
The main purpose of the study is to establish a safe dose of the drug by providing information on any potential side effects this drug may cause and collecting data about how a patient's cancer responds to the drug. The study will also assess the blood levels and action of AZD2014 in the body over a period of time and will indicate whether the drug has an effect on the types of cancer the patients have.
- Conditions
- Advanced Solid Malignancies
- Being tested
- AZD2014
- Keywords
- Phase I, cancer, advanced solid malignancies, dose escalation, AZD2014, mTor kinase inhibitor, safety, pharmacokinetics
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD2014Drug
Dose escalation phase: a single dose taken orally (solution or tablet) of AZD2014 on single dose day 1 (visit 2), followed by once or twice daily continuous dosing after a washout period (48 hours - 7 days) at visit 4, until discontinuation or withdrawal or Single or multiple doses taken orally (solution or tablet) of AZD2014 taken intermittently until discontinuation or withdrawal. Expansion phase: twice daily dosing from day 1 until discontinuation or withdrawal or a single dose taken orally of AZD2014 on single dose day 1 (visit 2), followed by a single dose on second single dose day 1 (visit 3) after a washout period (48 hours - 7 days) followed by once or twice daily continuous dosing after a washout period (48 hours - 7 days) at visit 4, until discontinuation or withdrawal or single or multiple doses taken orally (solution or tablet) of AZD2014 taken intermittently until discontinuation or withdrawal.
| Study group | Role | What they receive |
|---|---|---|
| AZD2014 | Experimental | AZD2014 dose escalation phase in Part A and expansion phase in Part B. Receives: Drug: AZD2014 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs)
Maximum Tolerated Dose (MTD) was determined by testing various doses and schedules of AZD2014 in cohorts of 3-6 evaluable patients. MTD reflects the highest dose of drug at each schedule that did not cause a DLT in >1 patient
Measured: Up to 21 days from first multiple dose
Secondary outcomes (15)
Best Objective Response
Best Objective Response per Response Evaluation Criteria in Solid Tumours Criteria (RECIST) 1.1 for target and non target lesions assessed by CT, MRI or X-ray; Complete Response (CR), Disappearance of all target lesions since baseline; Partial Response (PR), At least a 30 percent decrease in the sum of diameters of target lesions; Progressive Disease (PD), At least a 20 percent increase in the sum of diameters of target lesions and an absolute increase of at least 5mm
Measured: Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months
Maximum Concentration (Cmax) Single Dose
Maximum concentration following single dose (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Measured: Following Single Dose up to 12, 24 or 48 hours post dose
Area Under the Curve (AUC) Single Dose
Area under the curve following single dose Continuous dosing - AUC parameter used Intermittent dosing - AUC(0-12) used (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Measured: Following Single Dose up to 12, 24 or 48 hours post dose
Maximum Concentration (Cmax) at Steady State
Cmax at steady state (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Measured: Multiple dosing to steady state (up to 12 or 48 hours post dose)
Area Under the Curve (AUC) at Steady State
AUC at steady state Continuous dosing - AUCss used Intermittent dosing - Weekly AUC used (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Measured: Multiple dosing to steady state (up to 12 or 48 hours post dose)
Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose
Fraction dose excreted unchanged in the urine from 0-12 hours after a single dose (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Measured: Pre dose through to 12 hours post dose
Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State
Fraction dose excreted unchanged in the urine from 0-12 hours after dosing (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Measured: Pre dose through to 24 hours post dose
Urine PK - Renal Clearance (Renal CL) Single Dose
Renal Clearance (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Measured: Pre dose through to 24 hours post dose
Urine PK - Renal Clearance (Renal CL) at Steady State
Renal Clearance (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Measured: Pre dose through to 24 hours post dose
Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose
Phosphorylation levels of 4EBP1 from peripheral blood mononuclear cell (Patients with undetectable values at baseline have been excluded)
Measured: predose and 2 hours after a single dose
Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose
Phosphorylation levels of AKT from PRP (Patients with undetectable values at baseline have been excluded)
Measured: predose and 2 hours after a single dose
Partial Metabolic Response (PMR), Cycle 1
Partial metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)
Measured: Cycle 1 Day 8
Partial Metabolic Response (PMR), Cycle 2
Partial metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)
Measured: Cycle 2 Day 8
Complete Metabolic Response (CMR), Cycle 1
Complete metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)
Measured: Cycle 1 Day 8
Complete Metabolic Response (CMR), Cycle 2
Complete metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)
Measured: Cycle 2 Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionAug 2014
- Study completionAug 2014
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 Advanced 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr. Udai Banerji, Principal investigator, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PTElisabeth Oelmann, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01026402
- Sponsor's protocol ID
- D2270C00001
- Other IDs
- 2009-015244-42, 2009
- Status last verified
- Jan 2016
- First submitted
- 3 Dec 2009
- Last updated
- 11 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the mTor Kinase Inhibitor AZD2014 Administered Orally to Patients With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT01026402
- Acronym / sponsor ID
- D2270C00001
- Conditions
- Advanced Solid Malignancies
- Keywords
- Phase I, cancer, advanced solid malignancies, dose escalation, AZD2014, mTor kinase inhibitor, safety, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 172 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 4 Dec 2009 (estimated)
- Results
- Posted 11 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of the study is to establish a safe dose of the drug by providing information on any potential side effects this drug may cause and collecting data about how a patient's cancer responds to the drug. The study will also assess the blood levels and action of AZD2014 in the body over a period of time and will indicate whether the drug has an effect on the types of cancer the patients have.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AZD2014 | Experimental | Drug: AZD2014AZD2014 dose escalation phase in Part A and expansion phase in Part B. |
Who may qualify
- Ages
- 18 to 150 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Histological or cytological confirmation of a solid, malignant tumour that is refractory to standard therapies or for which no standard therapies exist
- At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computerised tomography (CT) magnetic resonance imaging (MRI) or plain X-ray and is suitable for repeated assessment
- World Health Organisation performance status 0-2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
Key exclusion criteria (3 listed)
- Patients with severe laboratory abnormalities for haematology, liver or renal function. Also treatment with any haemopoietic growth factors are not allowed within two weeks prior to first dose of study drug
- Patients with abnormal fasting glucose, type I or uncontrolled type II diabetes
- Patients with severe cardiac condition of ischemia, impaired ventricular function and arrhythmias, evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions
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 |
|---|---|---|
| AZD2014Dose escalation phase: a single dose taken orally (solution or tablet) of AZD2014 on single dose day 1 (visit 2), followed by once or twice daily continuous dosing after a washout period (48 hours - 7 days) at visit 4, until discontinuation or withdrawal or Single or multiple doses taken orally (solution or tablet) of AZD2014 taken intermittently until discontinuation or withdrawal. Expansion phase: twice daily dosing from day 1 until discontinuation or withdrawal or a single dose taken orally of AZD2014 on single dose day 1 (visit 2), followed by a single dose on second single dose day 1 (visit 3) after a washout period (48 hours - 7 days) followed by once or twice daily continuous dosing after a washout period (48 hours - 7 days) at visit 4, until discontinuation or withdrawal or single or multiple doses taken orally (solution or tablet) of AZD2014 taken intermittently until discontinuation or withdrawal. | Drug | AZD2014 |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Up to 21 days from first multiple dose
Maximum Tolerated Dose (MTD) was determined by testing various doses and schedules of AZD2014 in cohorts of 3-6 evaluable patients. MTD reflects the highest dose of drug at each schedule that did not cause a DLT in >1 patient
15 secondary outcomes
Best Objective Response
Time frame: Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months
Maximum Concentration (Cmax) Single Dose
Time frame: Following Single Dose up to 12, 24 or 48 hours post dose
Area Under the Curve (AUC) Single Dose
Time frame: Following Single Dose up to 12, 24 or 48 hours post dose
Maximum Concentration (Cmax) at Steady State
Time frame: Multiple dosing to steady state (up to 12 or 48 hours post dose)
Area Under the Curve (AUC) at Steady State
Time frame: Multiple dosing to steady state (up to 12 or 48 hours post dose)
Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose
Time frame: Pre dose through to 12 hours post dose
Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State
Time frame: Pre dose through to 24 hours post dose
Urine PK - Renal Clearance (Renal CL) Single Dose
Time frame: Pre dose through to 24 hours post dose
Urine PK - Renal Clearance (Renal CL) at Steady State
Time frame: Pre dose through to 24 hours post dose
Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose
Time frame: predose and 2 hours after a single dose
Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose
Time frame: predose and 2 hours after a single dose
Partial Metabolic Response (PMR), Cycle 1
Time frame: Cycle 1 Day 8
Partial Metabolic Response (PMR), Cycle 2
Time frame: Cycle 2 Day 8
Complete Metabolic Response (CMR), Cycle 1
Time frame: Cycle 1 Day 8
Complete Metabolic Response (CMR), Cycle 2
Time frame: Cycle 2 Day 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Advanced Solid Malignancies
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
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RecruitingPhase 1/2
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Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
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.
Dr. Udai Banerji principal investigator
The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT
Elisabeth Oelmann study director
AstraZeneca
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD2014 in people with Advanced Solid Malignancies, run by AstraZeneca at 2 sites 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 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in 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 11 Feb 2016). 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?
Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Up to 21 days from first multiple dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2016.