Advanced Solid Malignancy,Phase 1OAKNCT01895946

Comparison of Two Formulations of AZD5363 and the Effect of Food on Pharmacokinetic Exposure, Safety and Tolerability

A Phase 1 study testing AZD5363 in people with Advanced Solid Malignancy, and Safety and Tolerability,, run by AstraZeneca at 3 sites in 2 countries.

Completed

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

Official record

Search all trials

Trial summary

Comparison of Two Formulations of AZD5363 and the Effect of Food on Pharmacokinetic Exposure, Safety and Tolerability Read more about this study

Who is it for?: Ages 18 to 100 years
Conditions the study is for: Advanced Solid Malignancy,, Safety and Tolerability,, Pharmacokinetics, Pharmacodynamics,
What is being tested?: AZD5363
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 33 participants
Where: 3 sitesin 2 countries
Study dates: Dec 2013to Jul 2015
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 100 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Aged at least 18 years
The presence of a solid, malignant tumour, excluding lymphoma, that is resistance to standard therapies or for which no standard therapies exist
The presence of at least one lesion 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
Estimated life expectancy of more than 12 weeks

Who cannot join

Clinically significant abnormalities of glucose metabolism
Spinal cord compression or brain metastases unless asymptomatic, treated and stable (not requiring steroids)
Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and Human Immunodeficiency Virus (HIV)
Evidence of clinically significant cardiac abnormalities, uncontrolled hypotension, left ventricular ejection fraction below the lower limit of normal for the site or experience of significant cardiac interventional procedures
A bad reaction to AZD5363 or any drugs similar to it in structure or class

Trial locations and contacts

3 sites in 2 countries.

Country

City, postcode or hospital

3 sites in 2 countries

United Kingdom2 sites

Research Site
Manchester, M20 4BX
Research Site
Surrey, SM2 5PT

Other trials in United Kingdom

Netherlands1 site

Research Site
Amsterdam, 1066 CX

Other trials in Netherlands

About this study

Official title: A Phase I, Open-Label, Multicentre Study to Compare Two Dosage Formulations of AZD5363 and to Establish the Effect of Food on the Pharmacokinetic Exposure, Safety and Tolerability of AZD5363 in Patients With Advanced Solid Malignancies

Comparison of Two Formulations of AZD5363 and the Effect of Food on Pharmacokinetic Exposure, Safety and Tolerability

Read the detailed description

This study is designed to investigate the safety, tolerability and pharmacokinetics of a new drug, AZD5363, in patients with advanced cancer . This study will investigate how the body handles AZD5363 (ie, how quickly the body absorbs and removes the drug), the comparison of a capsule and a tablet formulation and the effect of food on AZD5363 tablet formulation.

Conditions: Advanced Solid Malignancy,, Safety and Tolerability,, Pharmacokinetics, Pharmacodynamics,, Tumour Response,
Being tested: AZD5363
Keywords: Advanced solid malignancy, AZD5363,, food effect,, formulation comparison

What participants receive

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

AZD5363Drug
Oral AZD5363 twice daily, 4 days on 3 days off: tablet formulation for one week, followed by two weeks with capsule formulation.
AZD5363Drug
Oral AZD5363 twice daily, 4 days on 3 days off, tablet formulation. On day 4 AZD5363 tablet without food. On day 11 AZD5363 tablet with food.

Study groups in NCT01895946
Study group	Role	What they receive
Part A: Formulation Switch	Experimental	AZD5363 tablet twice daily followed by AZD5363 capsule twice daily on an intermittent regimen (4 days on, 3 days off). Receives: Drug: AZD5363
Part B: Food effect	Experimental	AZD5363 tablet twice daily on an intermittent regimen (4 days on, 3 days off) with/without food on one occasion Receives: Drug: AZD5363

What is being measured

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

Ratio of Css,Max for Day 4 to Day 11
The actual sampling times were used in the pharmacokinetics (PK) parameter calculations and PK parameters were derived using standard non-compartmental methods.
Following the twice daily dosing in Cycle 1 at Day 4 and 11 for both the formulation switch and food effect investigations, the following PK parameters have been determined:
Maximum plasma concentration at steady state (Css max), time to Css,max (tss max), minimum plasma concentration at steady state (Css min), area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCss) and apparent clearance (CLss/F).
Css max, tss max were determined by inspection of the concentration-time profiles. AUCss was calculated using the linear up / log down trapezoidal rule. CLss/F was determined from the ratio of dose/AUCss.
Ratio of Css,max for Day 4 to Day 11 have been derived.
Measured: Day 4 and Day 11
Ratio of AUCss for Day 4 to Day 11
The actual sampling times were used in the parameter calculations and PK parameters were derived using standard non-compartmental methods.
Following the twice daily dosing in Cycle 1 at Day 4 and 11 for both the formulation switch and food effect investigations, the following PK parameters have been determined:
Css max, tss max, Css min, area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCss) and CLss/F.
Css max, tss max were determined by inspection of the concentration-time profiles. AUCss was calculated using the linear up / log down trapezoidal rule. CLss/F was determined from the ratio of dose/AUCss.
Ratio of AUCss for Day 4 to Day 11 have been derived.
Measured: Day 4 and Day 11

Secondary outcomes (5)

Efficacy: Best Objective Response (BOR)
Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 guidelines for measurable, non-measurable, target lesions (TLs) and non-target lesions (NTLs) and the objective tumour response criteria was used.
Categorisation of objective tumour response assessment was based on the RECIST 1.1 guidelines for response: CR (complete response, efined as disappearance of all target lesions), PR (partial response, defined as >=30% decrease in the sum of the longest diameter of target lesions), SD (stable disease, defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression) and PD (progression of disease, defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion). BOR was the best overall response observed across the study and up to 36 weeks. Number of subjects with response (CR or PR) is described.
Measured: Assessed every 6 weeks, up to 36 weeks
Efficacy: Disease Control at Week 12
Disease control = confirmed complete response + confirmed partial response + stable disease at 12 weeks
Measured: Week 12
Efficacy: Target Lesion Size, Percentage Change From Baseline at Week 12
Tumour size is the sum of the longest diameters of the target lesions. Target lesions are measurable tumour lesions.
The percentage change in target lesion tumour size at each week 12 for which data are available was obtained for each subject taking the difference between the sum of the target lesion at each week 12 and the sum of the target lesions at baseline divided by the sum of the target lesions at baseline multiplied by 100 (i.e. (week 12) - baseline)/baseline * 100).
Measured: Week 12
Efficacy: Target Lesion Size, Best Percentage Change From Baseline
Tumour size is the sum of the longest diameters of the target lesions. Target lesions are measurable tumour lesions.
best percentage change in tumour size from baseline is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction from baseline based on all post baseline assessments.
Measured: Assessed every 6 weeks up to 36 weeks
Efficacy: Progression-free Survival (PFS)
PFS is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the subject withdraws from randomised therapy or receives another anti-cancer therapy prior to progression. Subjects who have not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions.
Measured: Assessed every 6 weeks up to 36 weeks

Timeline

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

Dec 2013Jul 2015

First posted11 Jul 2013 (estimated)
Study startDec 2013
Primary completionFeb 2015
Study completionJul 2015

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 Malignancy,Studies 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: 33 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01895946
Sponsor's protocol ID: D3610C00007
Acronym: OAK
Status last verified: Apr 2016
First submitted: 21 Jun 2013
Last updated: 25 May 2016
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

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)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

All Advanced Solid Malignancy, trials

Study at a glance

From the registry record, last updated by the sponsor on 25 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open-Label, Multicentre Study to Compare Two Dosage Formulations of AZD5363 and to Establish the Effect of Food on the Pharmacokinetic Exposure, Safety and Tolerability of AZD5363 in Patients With Advanced Solid Malignancies
ClinicalTrials.gov ID: NCT01895946
Acronym / sponsor ID: OAK / D3610C00007
Conditions: Advanced Solid Malignancy,, Safety and Tolerability,, Pharmacokinetics, Pharmacodynamics,, Tumour Response,
Keywords: Advanced solid malignancy, AZD5363,, food effect,, formulation comparison
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 33 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Dec 2013
Primary completion: Feb 2015 (actual)
Study completion: Jul 2015 (actual)
First posted: 11 Jul 2013 (estimated)
Results: Posted 25 May 2016

Clinical summary

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

Comparison of Two Formulations of AZD5363 and the Effect of Food on Pharmacokinetic Exposure, Safety and Tolerability

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Part A: Formulation Switch	Experimental	Drug: AZD5363AZD5363 tablet twice daily followed by AZD5363 capsule twice daily on an intermittent regimen (4 days on, 3 days off).
Part B: Food effect	Experimental	Drug: AZD5363AZD5363 tablet twice daily on an intermittent regimen (4 days on, 3 days off) with/without food on one occasion

Who may qualify

Ages: 18 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Aged at least 18 years
The presence of a solid, malignant tumour, excluding lymphoma, that is resistance to standard therapies or for which no standard therapies exist
The presence of at least one lesion 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
Estimated life expectancy of more than 12 weeks

Key exclusion criteria (5 listed)

Clinically significant abnormalities of glucose metabolism
Spinal cord compression or brain metastases unless asymptomatic, treated and stable (not requiring steroids)
Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and Human Immunodeficiency Virus (HIV)
Evidence of clinically significant cardiac abnormalities, uncontrolled hypotension, left ventricular ejection fraction below the lower limit of normal for the site or experience of significant cardiac interventional procedures
A bad reaction to AZD5363 or any drugs similar to it in structure or class

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
AZD5363Oral AZD5363 twice daily, 4 days on 3 days off: tablet formulation for one week, followed by two weeks with capsule formulation.	Drug	Part A: Formulation Switch
AZD5363Oral AZD5363 twice daily, 4 days on 3 days off, tablet formulation. On day 4 AZD5363 tablet without food. On day 11 AZD5363 tablet with food.	Drug	Part B: Food effect

Primary outcome

Ratio of Css,Max for Day 4 to Day 11
Time frame: Day 4 and Day 11
The actual sampling times were used in the pharmacokinetics (PK) parameter calculations and PK parameters were derived using standard non-compartmental methods. Following the twice daily dosing in Cycle 1 at Day 4 and 11 for both the formulation switch and food effect investigations, the following PK parameters have been determined: Maximum plasma concentration at steady state (Css max), time to Css,max (tss max), minimum plasma concentration at steady state (Css min), area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCss) and apparent clearance (CLss/F). Css max, tss max were determined by inspection of the concentration-time profiles. AUCss was calculated using the linear up / log down trapezoidal rule. CLss/F was determined from the ratio of dose/AUCss. Ratio of Css,max for Day 4 to Day 11 have been derived.
Ratio of AUCss for Day 4 to Day 11
Time frame: Day 4 and Day 11
The actual sampling times were used in the parameter calculations and PK parameters were derived using standard non-compartmental methods. Following the twice daily dosing in Cycle 1 at Day 4 and 11 for both the formulation switch and food effect investigations, the following PK parameters have been determined: Css max, tss max, Css min, area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCss) and CLss/F. Css max, tss max were determined by inspection of the concentration-time profiles. AUCss was calculated using the linear up / log down trapezoidal rule. CLss/F was determined from the ratio of dose/AUCss. Ratio of AUCss for Day 4 to Day 11 have been derived.

5 secondary outcomes

Efficacy: Best Objective Response (BOR)
Time frame: Assessed every 6 weeks, up to 36 weeks
Efficacy: Disease Control at Week 12
Time frame: Week 12
Efficacy: Target Lesion Size, Percentage Change From Baseline at Week 12
Time frame: Week 12
Efficacy: Target Lesion Size, Best Percentage Change From Baseline
Time frame: Assessed every 6 weeks up to 36 weeks
Efficacy: Progression-free Survival (PFS)
Time frame: Assessed every 6 weeks up to 36 weeks

Results and safety

Results posted to the registry on 25 May 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A	18	18
Part B	12	12

Primary outcome: Ratio of Css,Max for Day 4 to Day 11

Time frame: Day 4 and Day 11. Geometric mean (90% Confidence Interval). Unit: Ratio

Measure	Part A n = 11	Part B n = 9
Value	1.02 (0.86 to 1.20)	0.67 (0.55 to 0.82)

Part A: Least square mean difference (LSM): 1.02 (90% CI 0.86 to 1.20), Mixed Models Analysis
Part B: Least square means difference (LSM): 0.67 (90% CI 0.55 to 0.82), Mixed Models Analysis

Population analysed: All patients who provided concentration-time data for AZD5363 for both capsule and tablet administration (Part A) or for both fed and fasted treatments and who were compliant with the standard dietary and evaluability requirements (Part B) were included in PK analysis set.

Primary outcome: Ratio of AUCss for Day 4 to Day 11

Time frame: Day 4 and Day 11. Geometric mean (90% Confidence Interval). Unit: Ratio

Measure	Part A n = 11	Part B n = 9
Value	0.90 (0.77 to 1.06)	0.89 (0.76 to 1.05)

Part A: Least square means difference (LSM): 0.90 (90% CI 0.77 to 1.06), Mixed Models Analysis
Part B: Least square means difference (LSM): 0.89 (90% CI 0.76 to 1.05), Mixed Models Analysis

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A	5 of 18 (27.8%)	18 of 18 (100%)	Not reported
Part B	6 of 12 (50%)	12 of 12 (100%)	Not reported

Limitations and caveats (from the sponsor): Small numbers of patients in the first (fasted) and second (fed) treatment periods overall make interpretation difficult.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Advanced Solid Malignancy,

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)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
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.

Justin Lindemann, MSD study director

AstraZeneca

Udai Banerji, MD, PhD principal investigator

Institute of Cancer Research, United Kingdom

3 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD5363 in people with Advanced Solid Malignancy, and Safety and Tolerability,, run by AstraZeneca at 3 sites in 2 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 4 inclusion and 5 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 25 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom, Netherlands. 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 25 May 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?

Ratio of Css,Max for Day 4 to Day 11 (time frame: Day 4 and Day 11). 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 NCT01895946.

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 25 May 2016.