FGFR Inhibition, Pharmacokinetics, BiomarkersPhase 1/2GLOWNCT01202591
Safety and Efficacy of AZD4547 in Combination With Fulvestrant vs. Fulvestrant Alone in ER+ Breast Cancer Patients
A Phase 1/2 study testing AZD4547, Exemestane and Fulvestrant in people with FGFR Inhibition, Pharmacokinetics, Biomarkers and ER+ Breast Cancer, run by AstraZeneca at 21 sites in 8 countries.
Trial summary
The purpose of this study is to assess the safety and effectiveness of AZD4547 in combination with fulvestrant vs. fulvestrant alone in ER+ breast cancer patients with FGFR1 polysomy (FISH4/5) or gene amplification (FISH 6) Read more about this study
- Who is it for?
- Ages 18 to 99 years, women only
- Conditions the study is for
- FGFR Inhibition, Pharmacokinetics, Biomarkers, ER+ Breast Cancer
- What is being tested?
- AZD4547, Exemestane and Fulvestrant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 127 participants
- Where
- 21 sitesin 8 countries
- Study dates
- Dec 2010to Oct 2014
- Phase
- Phase 1/2
- 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 99 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Post-menopausal women (either through bilateral oophorectomy or amenorrhoeic for 24 months)
- Histological confirmation of Breast Cancer with documented ER+ receptor status
- Safety run-in: Relapsing during/within 12 months of completion of a single regimen of adjuvant endocrine therapy with non-steroidal AI and/ tamoxifen or progression following 1st line endocrine therapy with non-steroidal AL
- Rand phase IIa: Received at least 1 prior endocrine therapy in the metastatic setting or have relapsed during/ within 6 months of completion of adjuvant endocrine therapy (either non-steroidal AI or tamoxifen or a combination of both). Chemotherapy administered in the adjuvant setting is permitted.
- Rand phase IIa: Mandatory provision of tumour sample to confirm FGFR1 polysomy or gene amplification. At least one measurable lesion that can be accurately assessed by CT/MRI/x-ray at baseline and follow up visits
Who cannot join
- Prior exposure to exemestane (safety run-in) / fulvestrant (randomized phase IIa), or any agent known to inhibit FGFRs.
- More than 1 prior regimen of chemotherapy for breast cancer
- ECG recordings that demonstrate significant abnormalities in cardiac rate, rhythm or conduction
- History of hypersensitivity to active or inactive excipients of AZD4547 or exemestane (safety run-in ) or fulvestrant (Randomized phase), including castor oil, or drugs with a similar chemical structure or class to AZD4547 or exemestane or fulvestrant.
- Randomized phase IIa: bleeding/blood clotting conditions that would prevent the administration of the fulvestrant injection into the buttocks
Trial locations and contacts
21 sites in 8 countries.
21 sites in 8 countries
United Kingdom5 sites
Research Site
Dundee
Research Site
London
Research Site
Manchester
Research Site
Oxford
Research Site
Sutton
Hungary4 sites
Research Site
Budapest
Research Site
Kaposvár
Research Site
Nyíregyháza
Research Site
Szeged
Germany3 sites
Research Site
Erlangen
Research Site
München
Research Site
Rostock
Italy3 sites
Research Site
Genova
Research Site
Lido di Camaiore
Research Site
Roma
About this study
Official title: A Randomised Double-blind Phase IIa Study (With Combination Safety Run-in) to Assess the Safety and Efficacy of AZD4547 in Combination With Fulvestrant vs. Fulvestrant Alone in ER+ Breast Cancer Patients With FGFR1 Polysomy or Gene Amplification Who Have Progressed Following Treatment With Prior Endocrine Therapy (Adjuvant or First-line Metastatic) (GLOW)
The purpose of this study is to assess the safety and effectiveness of AZD4547 in combination with fulvestrant vs. fulvestrant alone in ER+ breast cancer patients with FGFR1 polysomy (FISH4/5) or gene amplification (FISH 6)
- Being tested
- AZD4547, Exemestane, Placebo, Fulvestrant
- Keywords
- Breast Cancer, ER+, FGFR1, Exemestane, AZD4547, Fulvestrant
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4547Drug
Tablet oral twice daily
ExemestaneDrug
Tablet oral once daily
PlaceboDrug
Tablet oral twice daily
FulvestrantDrug
A monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration
| Study group | Role | What they receive |
|---|---|---|
| AZD4547 + exemestane | Experimental | Safety run-in: AZD4547 plus exemestane Receives: Drug: AZD4547; Drug: Exemestane |
| AZD4547 + fulvestrant | Experimental | A Randomised phase IIa: AZD4547 plus fulvestrant Receives: Drug: AZD4547; Drug: Fulvestrant |
| Placebo + fulvestrant | Placebo comparator | Randomised phase IIa: Matching placebo plus fulvestrant Receives: Drug: Placebo; Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability in Terms of Number of Patients With Adverse Events (Serious and Non-serious)
Measured: 3 years, 10 months (Adverse events recorded from patient screening to discontinuation plus 28 days safety follow-up).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2010 (estimated)
- Study startDec 2010
- Primary completionSep 2014
- Study completionOct 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 FGFR Inhibition, Pharmacokinetics, BiomarkersStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Donal Landers, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01202591
- Sponsor's protocol ID
- D2610C00003
- Other IDs
- 2010-021220-10
- Acronym
- GLOW
- Status last verified
- Jan 2016
- First submitted
- 14 Sep 2010
- 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 Randomised Double-blind Phase IIa Study (With Combination Safety Run-in) to Assess the Safety and Efficacy of AZD4547 in Combination With Fulvestrant vs. Fulvestrant Alone in ER+ Breast Cancer Patients With FGFR1 Polysomy or Gene Amplification Who Have Progressed Following Treatment With Prior Endocrine Therapy (Adjuvant or First-line Metastatic) (GLOW)
- ClinicalTrials.gov ID
- NCT01202591
- Acronym / sponsor ID
- GLOW / D2610C00003
- Keywords
- Breast Cancer, ER+, FGFR1, Exemestane, AZD4547, Fulvestrant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- Sep 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 16 Sep 2010 (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 purpose of this study is to assess the safety and effectiveness of AZD4547 in combination with fulvestrant vs. fulvestrant alone in ER+ breast cancer patients with FGFR1 polysomy (FISH4/5) or gene amplification (FISH 6)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AZD4547 + exemestane | Experimental | Drug: AZD4547, Drug: ExemestaneSafety run-in: AZD4547 plus exemestane |
| AZD4547 + fulvestrant | Experimental | Drug: AZD4547, Drug: FulvestrantA Randomised phase IIa: AZD4547 plus fulvestrant |
| Placebo + fulvestrant | Placebo comparator | Drug: Placebo, Drug: FulvestrantRandomised phase IIa: Matching placebo plus fulvestrant |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Post-menopausal women (either through bilateral oophorectomy or amenorrhoeic for 24 months)
- Histological confirmation of Breast Cancer with documented ER+ receptor status
- Safety run-in: Relapsing during/within 12 months of completion of a single regimen of adjuvant endocrine therapy with non-steroidal AI and/ tamoxifen or progression following 1st line endocrine therapy with non-steroidal AL
- Rand phase IIa: Received at least 1 prior endocrine therapy in the metastatic setting or have relapsed during/ within 6 months of completion of adjuvant endocrine therapy (either non-steroidal AI or tamoxifen or a combination of both). Chemotherapy administered in the adjuvant setting is permitted.
- Rand phase IIa: Mandatory provision of tumour sample to confirm FGFR1 polysomy or gene amplification. At least one measurable lesion that can be accurately assessed by CT/MRI/x-ray at baseline and follow up visits
Key exclusion criteria (5 listed)
- Prior exposure to exemestane (safety run-in) / fulvestrant (randomized phase IIa), or any agent known to inhibit FGFRs.
- More than 1 prior regimen of chemotherapy for breast cancer
- ECG recordings that demonstrate significant abnormalities in cardiac rate, rhythm or conduction
- History of hypersensitivity to active or inactive excipients of AZD4547 or exemestane (safety run-in ) or fulvestrant (Randomized phase), including castor oil, or drugs with a similar chemical structure or class to AZD4547 or exemestane or fulvestrant.
- Randomized phase IIa: bleeding/blood clotting conditions that would prevent the administration of the fulvestrant injection into the buttocks
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 |
|---|---|---|
| AZD4547Tablet oral twice daily | Drug | AZD4547 + exemestane, AZD4547 + fulvestrant |
| ExemestaneTablet oral once daily | Drug | AZD4547 + exemestane |
| PlaceboTablet oral twice daily | Drug | Placebo + fulvestrant |
| FulvestrantA monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration | Drug | AZD4547 + fulvestrant, Placebo + fulvestrant |
Primary outcome
Safety and Tolerability in Terms of Number of Patients With Adverse Events (Serious and Non-serious)
Time frame: 3 years, 10 months (Adverse events recorded from patient screening to discontinuation plus 28 days safety follow-up).
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.
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.
Donal Landers study director
AstraZeneca
21 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD4547, Exemestane and Fulvestrant in people with FGFR Inhibition, Pharmacokinetics, Biomarkers and ER+ Breast Cancer, run by AstraZeneca at 21 sites in 8 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 5 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 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 21 sites in United Kingdom, Hungary, Germany, Italy, Belgium and 3 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Safety and Tolerability in Terms of Number of Patients With Adverse Events (Serious and Non-serious) (time frame: 3 years, 10 months (Adverse events recorded from patient screening to discontinuation plus 28 days safety follow-up).). 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.