Phase I/II AZD8931/Paclitaxel in Treatment of Advanced Solid Tumours (Phase I) and Advanced Breast Cancer (Phase II) (THYME)
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| ClinicalTrials.gov Identifier: NCT00900627 |
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Recruitment Status :
Completed
First Posted : May 13, 2009
Results First Posted : September 29, 2014
Last Update Posted : January 20, 2016
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Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
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Brief 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. The second part (phase II) will determine the efficacy and safety of AZD8931 in combination with paclitaxel chemotherapy in breast cancer.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neoplasms Breast Neoplasms Breast Cancer | Drug: AZD8931 Drug: Paclitaxel Drug: Placebo | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 330 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Study Start Date : | June 2009 |
| Actual Primary Completion Date : | April 2012 |
| Actual Study Completion Date : | February 2015 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
Drug Information available for:
Paclitaxel
| Arm | Intervention/treatment |
|---|---|
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Experimental: 1
AZD8931 plus Paclitaxel
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Drug: AZD8931
Tablet Oral bid Drug: Paclitaxel IV once weekly for 3 weeks followed by a week off (repeated cycles)
Other Name: Taxol |
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Placebo Comparator: 2
Placebo plus Paclitaxel
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Drug: Paclitaxel
IV once weekly for 3 weeks followed by a week off (repeated cycles)
Other Name: Taxol Drug: Placebo Oral bid (twice daily) |
Primary Outcome Measures :
- 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)
Secondary Outcome Measures :
- 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 ]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))
- 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 ]The time from the date of randomization until the date of death due to any cause.
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| Ages Eligible for Study: | 18 Years to 150 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00900627
Locations
| Belgium | |
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| Brussels (Jette), Belgium | |
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| Leuven, Belgium | |
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| Namur, Belgium | |
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| Sint-Niklaas, Belgium | |
| Brazil | |
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| Sao Paulo, Brazil | |
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| São Paulo, Brazil | |
| Bulgaria | |
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| Sofia, Bulgaria | |
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| Stara Zagora, Bulgaria | |
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| Varna, Bulgaria | |
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| Vratza, Bulgaria | |
| Canada, Nova Scotia | |
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| Halifax, Nova Scotia, Canada | |
| Canada, Ontario | |
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| London, Ontario, Canada | |
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| Ottawa, Ontario, Canada | |
| Czech Republic | |
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| Brno, Czech Republic | |
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| Jicin, Czech Republic | |
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| Olomouc, Czech Republic | |
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| Praha 2, Czech Republic | |
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| Praha 4 - Krc, Czech Republic | |
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| Praha 4, Czech Republic | |
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| Znojmo, Czech Republic | |
| France | |
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| Villejuif Cedex, France | |
| Hungary | |
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| Budapest, Hungary | |
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| Debrecen, Hungary | |
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| Györ, Hungary | |
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| Szeged, Hungary | |
| Italy | |
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| Lido di Camaiore, Italy | |
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| Modena, Italy | |
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| Treviglio, Italy | |
| Panama | |
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| Ciudad de Panama, Panama | |
| Peru | |
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| Lima, Peru | |
| Spain | |
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| Barcelona, Spain | |
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| Madrid, Spain | |
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| Valencia, Spain | |
| Sweden | |
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| Uppsala, Sweden | |
| Switzerland | |
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| Chur, Switzerland | |
| United Kingdom | |
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| Glasgow, United Kingdom | |
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| Leicester, United Kingdom | |
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| London, United Kingdom | |
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| Nottingham, United Kingdom | |
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| Surrey, United Kingdom | |
Sponsors and Collaborators
AstraZeneca
Investigators
| Study Director: | Dr Serban Ghiorghiu | AstraZeneca | |
| Principal Investigator: | Professor Jose Baselga | Vall d'Hebron University Hospital |
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT00900627 |
| Other Study ID Numbers: |
D0102C00003 |
| First Posted: | May 13, 2009 Key Record Dates |
| Results First Posted: | September 29, 2014 |
| Last Update Posted: | January 20, 2016 |
| Last Verified: | January 2016 |
Keywords provided by AstraZeneca:
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Cancer Tumour Breast cancer Metastatic Secondary |
Additional relevant MeSH terms:
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Breast Neoplasms Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Paclitaxel |
Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |