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

Breast Cancer Clinical Trial

— THYME  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00900627
• Other study ID #: D0102C00003
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 12, 2009
• Last updated: January 15, 2016
• Start date: June 2009
• Est. completion date: February 2015

Study information

• Verified date: January 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Switzerland: SwissmedicSweden: Medical Products AgencyCanada: Health CanadaHungary: National Institute of PharmacyCzech Republic: State Institute for Drug ControlBulgaria: Bulgarian Drug AgencyColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosItaly: Ministry of HealthPeru: General Directorate of Pharmaceuticals, Devices, and DrugsPanama: Commemorative Institute GORGAS of Studies of HealthPanama: Ministry of HealthBrazil: National Health Surveillance Agency
• Study type: Interventional

Clinical 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. The second part (phase II) will determine the efficacy and safety of AZD8931 in combination with paclitaxel chemotherapy in breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: February 2015
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 150 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Neoplasms

Intervention

Drug:
• AZD8931
Tablet Oral bid
• Paclitaxel
IV once weekly for 3 weeks followed by a week off (repeated cycles)
• Placebo
Oral bid (twice daily)

Locations

Country	Name	City	State
Belgium	Research Site	Brussels (Jette)
Belgium	Research Site	Leuven
Belgium	Research Site	Namur
Belgium	Research Site	Sint-Niklaas
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Vratza
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	London	Ontario
Canada	Research Site	Ottawa	Ontario
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Jicin
Czech Republic	Research Site	Olomouc
Czech Republic	Research Site	Praha 2
Czech Republic	Research Site	Praha 4
Czech Republic	Research Site	Praha 4 - Krc
Czech Republic	Research Site	Znojmo
France	Research Site	Villejuif Cedex
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Györ
Hungary	Research Site	Szeged
Italy	Research Site	Lido di Camaiore
Italy	Research Site	Modena
Italy	Research Site	Treviglio
Panama	Research Site	Ciudad de Panama
Peru	Research Site	Lima
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Valencia
Sweden	Research Site	Uppsala
Switzerland	Research Site	Chur
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Belgium,  Brazil,  Bulgaria,  Canada,  Czech Republic,  France,  Hungary,  Italy,  Panama,  Peru,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Weekly visits for routine safety monitoring from Day 1 to Day 28 for each participant	No
Primary	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)	Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012	No
Secondary	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))	Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012	No
Secondary	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.	Weekly visits for routine safety monitoring, accessed up to data cut off on 11th April 2012	No