CancerPhase 1NCT00979134

Study is Designed to Assess the Safety and Tolerability of AZD4547 at Increasing Doses in Patients With Advanced Tumours

A Phase 1 study testing AZD4547 in people with Cancer and Advanced Solid Malignancies, run by AstraZeneca at 29 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This study is primarily designed to assess the safety and tolerability of AZD4547 at increasing doses in patients with advanced solid malignancies and for whom no standard medication options are available. It also assesses the blood levels and action of AZD4547 in the body over a period of time. Read more about this study

Who is it for?: Ages 25 to 149 years
Conditions the study is for: Cancer, Advanced Solid Malignancies
What is being tested?: AZD4547
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 95 participants
Where: 29 sitesin 7 countries
Study dates: 21 Oct 2009to 5 Mar 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 25 to 149 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Minimum life expectancy of 12 weeks
The presence of a solid, malignant tumour that is resistance to standard therapies or for which no standard therapies exist
In the expansion for the study patients must have a tumour at least 1cm in size that can be measure using a CT or MRI scan, and provide a tumour sample to the sponsor company for testing of FGFR1 and/or 2 amplification
Expansion, 5 groups of advanced cancer
Solid tumours,FGFR1 and/or FGFR2 gene amplified
Squamous NSCLC, FGFR1 gene low \& high amplified
Gastric adenocarcinoma, including the lower oesophagus/gastro-oesophageal junction, FGFR2 gene low \& high amplified
Aged at least 25 years

Who cannot join

Treatment with any other chemotherapy, immunotherapy or anticancer agents within 3 weeks before the first dose of study
An inability to be able to take the study medication
A bad reaction to AZD4547 or any drugs similar to it in structure or class.

Trial locations and contacts

29 sites in 7 countries.

Country

City, postcode or hospital

29 sites in 7 countries

United States8 sites

Research Site
Aurora, Colorado, 80045
Research Site
Detroit, Michigan, 48201
Research Site
Houston, Texas, 77030
Research Site
Nashville, Tennessee, 37232
Research Site
New Haven, Connecticut, 06520
Research Site
New York, New York, 10021
Research Site
Philadelphia, Pennsylvania, 19111
Research Site
Stanford, California, 94305

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United Kingdom8 sites

Research Site
Birmingham, B9 5SS
Research Site
Edinburgh, EH4 2XU
Research Site
Glasgow, G12 0YN
Research Site
London, W12 0NN
Research Site
London, W1G 6AD
Research Site
Manchester, M20 4BX
Research Site
Newcastle upon Tyne, NE7 7DN
Research Site
Wolverhampton, WV10 0QP

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Spain4 sites

Research Site
Badajoz, 06008
Research Site
Majadahonda, 28222
Research Site
Valencia, 46010
Research Site
Valencia, 46026

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Germany3 sites

Research Site
Cologne, 50924
Research Site
Frankfurt, 60488
Research Site
Freiburg im Breisgau, 79106

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France2 sites

Research Site
Pierre-Bénite, 69495
Research Site
Villejuif, 94805

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Italy2 sites

Research Site
Naples, 80131
Research Site
Rozzano, 20089

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Netherlands2 sites

Research Site
Amsterdam, 1066 CX
Research Site
Rotterdam, 3015 CE

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About this study

Official title: A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD4547 in Patients With Advanced Solid Malignancies

Conditions: Cancer, Advanced Solid Malignancies
Being tested: AZD4547
Keywords: Cancer, Tumour, Advanced Solid Malignancies, FGFR, Squamous NSCLC, Gastric adenocarcinoma
Medical subject headings: Neoplasms

What participants receive

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

AZD4547Drug
Single dose is followed by washout 5-10 days before multiple dose, and at dose of 80mg twice daily
AZD4547Drug
Patients start at a dose of 80 mg twice daily, with no washout
AZD4547Drug
Single dose is followed by washout 5-10 days before multiple dose

Study groups in NCT00979134
Study group	Role	What they receive
Part A	Experimental	Ascending doses of AZD4547 administered orally to patients to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD) Receives: Drug: AZD4547
Part B	Experimental	Dose expansion phase, at the RD defined in Part A Receives: Drug: AZD4547
Part C	Experimental	Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A Receives: Drug: AZD4547

What is being measured

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

Number of Patients Who Experienced at Least 1 AE
To investigate the safety and tolerability of AZD4547. System organ class (SOC), preferred term (PT), duration and severity all recorded.
Measured: AEs are monitored from screenng through to 30 day follow up period
Number of Participants Who Experienced at Least 1 Causally Related AE.
To investigate the safety and tolerability of AZD4547. A causally related AE is an AE deemed to be causally related to AZD4547.
Measured: AEs are continually assessed from screening up to 30 day FU period
Number of Participants With at Least 1 AE of CTCAE >=G3
To investigate the safety and tolerability of AZD4547
Measured: Ongoing up to discontinuation up to 30 day FU.
Number of Participants With at Least 1 Causally Related AE of CTCAE >=G3
To investigate the safety and tolerability of AZD4547
Measured: Ongoing up to discontinuation up to 30 day FU.
Number of Participants Who Experienced at Least One SAE
To investigate the safety and tolerability of AZD4547. A SAE (Serious Adverse Event) is and AE (adverse Event) which fulfills one of the following criteria that the PI assesses closely such as results in death, immediately life-threatening, requires hospitalisation or prolongation of, results in significant disability, results in birth defect, may jepardise the patient or require intervention to prevent any of the previous outcomes.
Measured: Serious Adverse Events (SAEs) are continually assessed from Screening up to the end of the 30 day FU period.
Number of Participants With at Least 1 Causally Related SAE
To investigate the safety and tolerability of AZD4547: SAEs are assessed and deemed as causally related or not to AZD4547
Measured: SAEs are continually monitored from screening to end of 30 FU period

Secondary outcomes (5)

AUC(0-infinity)
To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
Measured: PK samples out to 96 hours "0 to 96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.
Tumour Response (Best Objective Response) - Number of Patients With a Confirmed Response of Partial Response (PR) or Confirmed Response (CR)
To obtain a preliminary assessment of the anti tumour activity of AZD4547 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1. Objective response = CR + PR; CR=disappearance of all target lesions and PR is >=30% reduction in sum of longest diameter of target lesions
Measured: Baseline assessment, then assessment every 6 weeks after start of treatment until objective disease progression.
Cmax (ng/mL)
To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
Measured: PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.
Css,Max (ng/mL)
To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
Measured: PK samples out to 96 hours "0-96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.
AUC,ss(0-infinity)
To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
Measured: PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.

Timeline

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

21 Oct 20095 Mar 2015

First posted17 Sep 2009 (estimated)
Study start21 Oct 2009
Primary completion12 Feb 2014
Study completion5 Mar 2015

Why it stopped: Termination of study enrolment to Part C, Cohort 3 (08 July 2013) was based on the analysis of data from Study D2610C00004. Data were available from 33 patient

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 CancerStudies 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: 95 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00979134
Sponsor's protocol ID: D2610C00001
Status last verified: Nov 2018
First submitted: 16 Sep 2009
Last updated: 15 Mar 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?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Mar 2019. 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 Anti-tumour Activity of Ascending Doses of AZD4547 in Patients With Advanced Solid Malignancies
ClinicalTrials.gov ID: NCT00979134
Acronym / sponsor ID: D2610C00001
Conditions: Cancer, Advanced Solid Malignancies
Keywords: Cancer, Tumour, Advanced Solid Malignancies, FGFR, Squamous NSCLC, Gastric adenocarcinoma
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Termination of study enrolment to Part C, Cohort 3 (08 July 2013) was based on the analysis of data from Study D2610C00004. Data were available from 33 patient
Enrolment: 95 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 21 Oct 2009 (actual)
Primary completion: 12 Feb 2014 (actual)
Study completion: 5 Mar 2015 (actual)
First posted: 17 Sep 2009 (estimated)
Results: Posted 15 Mar 2019

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Part A	Experimental	Drug: AZD4547Ascending doses of AZD4547 administered orally to patients to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD)
Part B	Experimental	Drug: AZD4547Dose expansion phase, at the RD defined in Part A
Part C	Experimental	Drug: AZD4547Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A

Who may qualify

Ages: 25 to 149 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Minimum life expectancy of 12 weeks
The presence of a solid, malignant tumour that is resistance to standard therapies or for which no standard therapies exist
In the expansion for the study patients must have a tumour at least 1cm in size that can be measure using a CT or MRI scan, and provide a tumour sample to the sponsor company for testing of FGFR1 and/or 2 amplification
Expansion, 5 groups of advanced cancer
Solid tumours,FGFR1 and/or FGFR2 gene amplified

Key exclusion criteria (3 listed)

Treatment with any other chemotherapy, immunotherapy or anticancer agents within 3 weeks before the first dose of study
An inability to be able to take the study medication
A bad reaction to AZD4547 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
AZD4547Single dose is followed by washout 5-10 days before multiple dose, and at dose of 80mg twice daily	Drug	Part B
AZD4547Patients start at a dose of 80 mg twice daily, with no washout	Drug	Part C
AZD4547Single dose is followed by washout 5-10 days before multiple dose	Drug	Part A

Primary outcome

Number of Patients Who Experienced at Least 1 AE
Time frame: AEs are monitored from screenng through to 30 day follow up period
To investigate the safety and tolerability of AZD4547. System organ class (SOC), preferred term (PT), duration and severity all recorded.
Number of Participants Who Experienced at Least 1 Causally Related AE.
Time frame: AEs are continually assessed from screening up to 30 day FU period
To investigate the safety and tolerability of AZD4547. A causally related AE is an AE deemed to be causally related to AZD4547.
Number of Participants With at Least 1 AE of CTCAE >=G3
Time frame: Ongoing up to discontinuation up to 30 day FU.
To investigate the safety and tolerability of AZD4547
Number of Participants With at Least 1 Causally Related AE of CTCAE >=G3
Time frame: Ongoing up to discontinuation up to 30 day FU.
To investigate the safety and tolerability of AZD4547
Number of Participants Who Experienced at Least One SAE
Time frame: Serious Adverse Events (SAEs) are continually assessed from Screening up to the end of the 30 day FU period.
To investigate the safety and tolerability of AZD4547. A SAE (Serious Adverse Event) is and AE (adverse Event) which fulfills one of the following criteria that the PI assesses closely such as results in death, immediately life-threatening, requires hospitalisation or prolongation of, results in significant disability, results in birth defect, may jepardise the patient or require intervention to prevent any of the previous outcomes.
Number of Participants With at Least 1 Causally Related SAE
Time frame: SAEs are continually monitored from screening to end of 30 FU period
To investigate the safety and tolerability of AZD4547: SAEs are assessed and deemed as causally related or not to AZD4547

5 secondary outcomes

AUC(0-infinity)
Time frame: PK samples out to 96 hours "0 to 96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.
Tumour Response (Best Objective Response) - Number of Patients With a Confirmed Response of Partial Response (PR) or Confirmed Response (CR)
Time frame: Baseline assessment, then assessment every 6 weeks after start of treatment until objective disease progression.
Cmax (ng/mL)
Time frame: PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.
Css,Max (ng/mL)
Time frame: PK samples out to 96 hours "0-96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.
AUC,ss(0-infinity)
Time frame: PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.

Results and safety

Results posted to the registry on 15 Mar 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
Part A	43	10
Part B	6	0
Part C	45	5

Primary outcome: Number of Patients Who Experienced at Least 1 AE

Time frame: AEs are monitored from screenng through to 30 day follow up period. Number. Unit: Participants

Measure	Part B n = 6	Part C (FISH Ratio >= 2) n = 33	Part C (FISH Ratio <2) n = 12	Part A n = 43
Value	6	33	12	43

Primary outcome: Number of Participants Who Experienced at Least 1 Causally Related AE.

Time frame: AEs are continually assessed from screening up to 30 day FU period. Number. Unit: Participants

Measure	Part B n = 6	Part C (FISH Ratio >= 2) n = 33	Part C (FISH Ratio <2) n = 12	Part A n = 43
Value	6	31	10	42

Primary outcome: Number of Participants With at Least 1 AE of CTCAE >=G3

Time frame: Ongoing up to discontinuation up to 30 day FU.. Number. Unit: Participants

Measure	Part B n = 6	Part C (FISH Ratio >= 2) n = 33	Part C (FISH Ratio <2) n = 12	Part A n = 43
Value	1	16	5	17

Primary outcome: Number of Participants With at Least 1 Causally Related AE of CTCAE >=G3

Time frame: Ongoing up to discontinuation up to 30 day FU.. Number. Unit: Participants

Measure	Part B n = 6	Part C (FISH Ratio >= 2) n = 33	Part C (FISH Ratio <2) n = 12	Part A n = 43
Value	0	8	3	12

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs were collected on a continual basis from Screening up until the end of the 28 day follow up period.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part B	1 of 6 (16.7%)	6 of 6 (100%)	Not reported
Part C (FISH Ratio >= 2)	10 of 33 (30.3%)	33 of 33 (100%)	Not reported
Part C (FISH Ratio < 2)	3 of 12 (25%)	12 of 12 (100%)	Not reported
Part A	11 of 43 (25.6%)	43 of 43 (100%)	Not reported

Limitations and caveats (from the sponsor): Due to early termination no AUC(inf), Cmax, Css,max and AUC,ss for Part C (PK). Data from 33 patients after 22 days of multiple dosing in Part A \& limited data for part B only. 1 subject not dosed, so pre-stated subject number 95, total with data 94.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 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.

Fabrice André, Dr principal investigator

Institut de cancérologie Gustave Roussy

Donal Landers, Dr study director

AstraZeneca

29 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD4547 in people with Cancer and Advanced Solid Malignancies, run by AstraZeneca at 29 sites in 7 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 8 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: stopped early, as of the sponsor's last update on 15 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States, United Kingdom, Spain, Germany, France and 2 more countries. 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 15 Mar 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?

Number of Patients Who Experienced at Least 1 AE (time frame: AEs are monitored from screenng through to 30 day follow up period). The study lists 6 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 NCT00979134.

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 15 Mar 2019.