NeoplasmsPhase 1/2THYMENCT00900627

Phase I/II AZD8931/Paclitaxel in Treatment of Advanced Solid Tumours (Phase I) and Advanced Breast Cancer (Phase II)

A Phase 1/2 study testing AZD8931 and Paclitaxel in people with Neoplasms and Breast Neoplasms, run by AstraZeneca at 38 sites in 14 countries.

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

The main purpose of this study is to determine if AZD8931 can improve the efficacy of standard chemotherapy for the treatment of advanced breast cancer. This study will be conducted in 2 parts: the first part (phase I) will determine a dose of AZD8931 that can be safely administered with paclitaxel chemotherapy. Read more about this study

Who is it for?: Ages 18 to 150 years
Conditions the study is for: Neoplasms, Breast Neoplasms, Breast Cancer
What is being tested?: AZD8931 and Paclitaxel
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: 330 participants
Where: 38 sitesin 14 countries
Study dates: Jun 2009to Feb 2015
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 150 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male/ female with solid, malignant tumour which is unresponsive to standard therapies (Phase I). Female patients with advanced breast cancer with low HER2 expression (Phase II)
Suitable for paclitaxel chemotherapy
Life expectancy more than 12 weeks

Who cannot join

Inadequate kidney, liver, heart, gastric, lung or eye function
Hypersensitive to paclitaxel
No symptomatic uncontrolled brain metastases
Previous taxane chemotherapy within 12 months (Phase II)

Trial locations and contacts

38 sites in 14 countries.

Country

City, postcode or hospital

38 sites in 14 countries

Czechia6 sites

Research Site
Brno
Research Site
Jičín
Research Site
Olomouc
Research Site
Prague
Research Site
Praha 4 - Krc
Research Site
Znojmo

Other trials in Czechia

United Kingdom5 sites

Research Site
Glasgow
Research Site
Leicester
Research Site
London
Research Site
Nottingham
Research Site
Surrey

Other trials in United Kingdom

Belgium4 sites

Research Site
Brussels (Jette)
Research Site
Leuven
Research Site
Namur
Research Site
Sint-Niklaas

Other trials in Belgium

Bulgaria4 sites

Research Site
Sofia
Research Site
Stara Zagora
Research Site
Varna
Research Site
Vratsa

Other trials in Bulgaria

Hungary4 sites

Research Site
Budapest
Research Site
Debrecen
Research Site
Győr
Research Site
Szeged

Other trials in Hungary

Canada3 sites

Research Site
Halifax, Nova Scotia
Research Site
London, Ontario
Research Site
Ottawa, Ontario

Other trials in Canada

Italy3 sites

Research Site
Lido di Camaiore
Research Site
Modena
Research Site
Treviglio

Other trials in Italy

Spain3 sites

Research Site
Barcelona
Research Site
Madrid
Research Site
Valencia

Other trials in Spain

Brazil1 site

Research Site
São Paulo

Other trials in Brazil

France1 site

Research Site
Villejuif

Other trials in France

Panama1 site

Research Site
Panama City

Other trials in Panama

Peru1 site

Research Site
Lima

Other trials in Peru

Sweden1 site

Research Site
Uppsala

Other trials in Sweden

Switzerland1 site

Research Site
Chur

Other trials in Switzerland

About this study

Official title: A Phase I/II Multi-centre Study of AZD8931 in Combination With Weekly Paclitaxel to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy in Patients With Advanced Solid Tumours and in a Selected Population With Low HER2-expressing Locally Recurrent and/or Metastatic Breast Cancer

Conditions: Neoplasms, Breast Neoplasms, Breast Cancer
Being tested: AZD8931, Paclitaxel, Placebo
Keywords: Cancer, Tumour, Breast cancer, Metastatic, Secondary
Medical subject headings: Neoplasms, Breast Neoplasms, Neoplasm Metastasis

What participants receive

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

AZD8931Drug
Tablet Oral bid
PaclitaxelDrug
Also called Taxol
IV once weekly for 3 weeks followed by a week off (repeated cycles)
PlaceboDrug
Oral bid (twice daily)

Study groups in NCT00900627
Study group	Role	What they receive
1	Experimental	AZD8931 plus Paclitaxel Receives: Drug: AZD8931; Drug: Paclitaxel
2	Placebo comparator	Placebo plus Paclitaxel Receives: Drug: Paclitaxel; Drug: Placebo

What is being measured

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

Phase I: The Number of Dose Limiting Toxicities in AZD8931 in Combination With Weekly Paclitaxel
DLT is an AE or laboratory abnormality related to AZD8931, starting during the DLT evaluation period and meeting any of the following criteria (further detail in protocol): Symptomatic ocular surface lesion; CTCAE grade 4 haematological AE; CTCAE grade ≥3 of febrile neutropenia / neutropenia / thrombocytopenia / hyperkalaemia / hyperglycaemia / hypotension / urological toxicity / ILD / pneumonitis; QTcF interval > 500 msec, two ECGs ≥ 30 minutes apart; Symptomatic congestive cardiac failure and a drop in LVEF; Decrease in LVEF of ≥20% to below the LLN; CS rash remaining CTCAE grade ≥3 for ≥5 days despite optimal treatment; CTCAE grade ≥3 nausea, vomiting or diarrhoea, despite optimal therapy; Other CTCAE grade ≥3 toxicity which, in the opinion of the investigator, is CS and related to AZD8931; Delay to the administration of paclitaxel on D1 of Cycle 2 by ≥7 days. Patients could have more than one DLT.
Measured: Weekly visits for routine safety monitoring from Day 1 to Day 28 for each participant
Phase II: Progression-free-survival (PFS) Were Analyzed in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone
Time from the date of randomization until the date of objective disease progression (as per RECIST 1.1) or the date of death (by any cause in the absence of progression)
Measured: Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012

Secondary outcomes (2)

Phase II: Objective Tumour Response Rate (ORR) Was Compared in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone
The number of subjects with at least one visit response of CR or PR (Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD), A ≥ 20% increase in the sum of diameters of target lesions and an absolute increase of ≥ 5mm; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Not Evaluable (NE), All target lesion measurements are missing or >1/3 target lesion measurements are missing and sum of diameters of non-missing target lesions does not qualify for PD; Not applicable (NA), No target lesions are recorded at baseline))
Measured: Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012
Phase II: The Overall Survival (OS) Was Compared in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone
The time from the date of randomization until the date of death due to any cause.
Measured: Weekly visits for routine safety monitoring, accessed up to data cut off on 11th April 2012

Timeline

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

Jun 2009Feb 2015

First posted13 May 2009 (estimated)
Study startJun 2009
Primary completionApr 2012
Study completionFeb 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 NeoplasmsStudies 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: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 330 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00900627
Sponsor's protocol ID: D0102C00003
Acronym: THYME
Status last verified: Jan 2016
First submitted: 12 May 2009
Last updated: 20 Jan 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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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All Neoplasms trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Multi-centre Study of AZD8931 in Combination With Weekly Paclitaxel to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy in Patients With Advanced Solid Tumours and in a Selected Population With Low HER2-expressing Locally Recurrent and/or Metastatic Breast Cancer
ClinicalTrials.gov ID: NCT00900627
Acronym / sponsor ID: THYME / D0102C00003
Conditions: Neoplasms, Breast Neoplasms, Breast Cancer
Keywords: Cancer, Tumour, Breast cancer, Metastatic, Secondary
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 330 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Jun 2009
Primary completion: Apr 2012 (actual)
Study completion: Feb 2015 (actual)
First posted: 13 May 2009 (estimated)
Results: Posted 29 Sep 2014

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: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: AZD8931, Drug: PaclitaxelAZD8931 plus Paclitaxel
2	Placebo comparator	Drug: Paclitaxel, Drug: PlaceboPlacebo plus Paclitaxel

Who may qualify

Ages: 18 to 150 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Male/ female with solid, malignant tumour which is unresponsive to standard therapies (Phase I). Female patients with advanced breast cancer with low HER2 expression (Phase II)
Suitable for paclitaxel chemotherapy
Life expectancy more than 12 weeks

Key exclusion criteria (4 listed)

Inadequate kidney, liver, heart, gastric, lung or eye function
Hypersensitive to paclitaxel
No symptomatic uncontrolled brain metastases
Previous taxane chemotherapy within 12 months (Phase II)

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
AZD8931Tablet Oral bid	Drug	1
PaclitaxelAlso: TaxolIV once weekly for 3 weeks followed by a week off (repeated cycles)	Drug	1, 2
PlaceboOral bid (twice daily)	Drug	2

Primary outcome

Phase I: The Number of Dose Limiting Toxicities in AZD8931 in Combination With Weekly Paclitaxel
Time frame: Weekly visits for routine safety monitoring from Day 1 to Day 28 for each participant
DLT is an AE or laboratory abnormality related to AZD8931, starting during the DLT evaluation period and meeting any of the following criteria (further detail in protocol): Symptomatic ocular surface lesion; CTCAE grade 4 haematological AE; CTCAE grade ≥3 of febrile neutropenia / neutropenia / thrombocytopenia / hyperkalaemia / hyperglycaemia / hypotension / urological toxicity / ILD / pneumonitis; QTcF interval > 500 msec, two ECGs ≥ 30 minutes apart; Symptomatic congestive cardiac failure and a drop in LVEF; Decrease in LVEF of ≥20% to below the LLN; CS rash remaining CTCAE grade ≥3 for ≥5 days despite optimal treatment; CTCAE grade ≥3 nausea, vomiting or diarrhoea, despite optimal therapy; Other CTCAE grade ≥3 toxicity which, in the opinion of the investigator, is CS and related to AZD8931; Delay to the administration of paclitaxel on D1 of Cycle 2 by ≥7 days. Patients could have more than one DLT.
Phase II: Progression-free-survival (PFS) Were Analyzed in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone
Time frame: Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012
Time from the date of randomization until the date of objective disease progression (as per RECIST 1.1) or the date of death (by any cause in the absence of progression)

2 secondary outcomes

Phase II: Objective Tumour Response Rate (ORR) Was Compared in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone
Time frame: Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012
Phase II: The Overall Survival (OS) Was Compared in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone
Time frame: Weekly visits for routine safety monitoring, accessed up to data cut off on 11th April 2012

Results and safety

Results posted to the registry on 29 Sep 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AZD8931 160 mg bd	6	0
AZD8931 120 mg bd	2	0
AZD8931 80 mg bd	6	0
AZD8931 40 mg bd	6	0
AZD8931 40MG bd + Paclitaxel	94	65
Placebo + Paclitaxel	96	70

Primary outcome: Phase I: The Number of Dose Limiting Toxicities in AZD8931 in Combination With Weekly Paclitaxel

Time frame: Weekly visits for routine safety monitoring from Day 1 to Day 28 for each participant. Number. Unit: Number of Dose Limiting Toxicities

Measure	AZD8931 160 mg bd n = 6	AZD8931 120 mg bd n = 2	AZD8931 80 mg bd n = 6
Total	2	1	2
Eye disorders: Keratitis	1	0	0
Eye disorders: Photophobia	1	0	0
Gastrointestinal disorders: Diarrhoea	1	1	0
Gastrointestinal disorders: Oesophagitis	0	0	1
Infections and infestations: Rash pustular	0	0	1

AZD8931 160 mg bd vs AZD8931 120 mg bd vs AZD8931 80 mg bd vs AZD8931 40 mg bd: Maximum Tolerated Dose: 40

Population analysed: Safety population (all participants who received at least one dose)

Primary outcome: Phase II: Progression-free-survival (PFS) Were Analyzed in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone

Time frame: Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012. Median (Inter-Quartile Range). Unit: Months

Measure	AZD8931 40MG bd + Paclitaxel n = 94	Placebo + Paclitaxel n = 96
Value	8.7 (4.2 to 12.9)	9.1 (3.4 to 14.8)

AZD8931 40MG bd + Paclitaxel vs Placebo + Paclitaxel: Hazard Ratio (HR): 1.08 (95% CI 0.76 to 1.52), p = 0.679, Cox Proportional Hazard model

Population analysed: Full Analysis Set

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs will be collected from time of signed informed consent throughout the treatment period and including the 30-day safety follow up period after the last dose of study treatment. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AZD8931 40 mg bd	4 of 6 (66.7%)	6 of 6 (100%)	Not reported
AZD8931 80 mg bd	2 of 6 (33.3%)	6 of 6 (100%)	Not reported
AZD8931 120 mg bd	1 of 2 (50%)	2 of 2 (100%)	Not reported
AZD8931 160 mg bd	3 of 6 (50%)	6 of 6 (100%)	Not reported
AZD8931 40MG bd + Paclitaxel	24 of 94 (25.5%)	93 of 94 (98.9%)	Not reported
Placebo + Paclitaxel	14 of 95 (14.7%)	94 of 95 (98.9%)	Not reported

Limitations and caveats (from the sponsor): 1. The primary statistical analysis of PFS was performed, but the planned analyses of overall survival at 50% maturity, and of PFS at 50% OS maturity, were not performed. 2. AEs were coded using MedDRA v14.0 (part A) and MedDRA v15.0 (part B).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2016.
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.

Dr Serban Ghiorghiu study director

AstraZeneca

Professor Jose Baselga principal investigator

Vall d'Hebron University Hospital

38 sites in 14 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AZD8931 and Paclitaxel in people with Neoplasms and Breast Neoplasms, run by AstraZeneca at 38 sites in 14 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 3 inclusion and 4 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 20 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in Czechia, United Kingdom, Belgium, Bulgaria, Hungary and 9 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 29 Sep 2014). 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?

Phase I: The Number of Dose Limiting Toxicities in AZD8931 in Combination With Weekly Paclitaxel (time frame: Weekly visits for routine safety monitoring from Day 1 to Day 28 for each participant). 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 NCT00900627.

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 20 Jan 2016.