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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00900627
First received: May 12, 2009
Last updated: June 12, 2015
Last verified: June 2015
  Purpose

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 Intervention Phase
Neoplasms
Breast Neoplasms
Breast Cancer
Drug: AZD8931
Drug: Paclitaxel
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The time from the date of randomization until the date of death due to any cause.


Enrollment: 330
Study Start Date: June 2009
Study Completion Date: February 2015
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
AZD8931 plus Paclitaxel
Drug: AZD8931
Tablet Oral bid
Drug: Paclitaxel
IV once weekly for 3 weeks followed by a week off (repeated cycles)
Other Name: Taxol
Placebo Comparator: 2
Placebo plus Paclitaxel
Drug: Paclitaxel
IV once weekly for 3 weeks followed by a week off (repeated cycles)
Other Name: Taxol
Drug: Placebo
Oral bid (twice daily)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00900627

  Show 40 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Dr Serban Ghiorghiu AstraZeneca
Principal Investigator: Professor Jose Baselga Vall d'Hebron University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00900627     History of Changes
Other Study ID Numbers: D0102C00003
Study First Received: May 12, 2009
Results First Received: January 31, 2014
Last Updated: June 12, 2015
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Switzerland: Swissmedic
Sweden: Medical Products Agency
Canada: Health Canada
Hungary: National Institute of Pharmacy
Czech Republic: State Institute for Drug Control
Bulgaria: Bulgarian Drug Agency
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Italy: Ministry of Health
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Panama: Commemorative Institute GORGAS of Studies of Health
Panama: Ministry of Health
Brazil: National Health Surveillance Agency

Keywords provided by AstraZeneca:
Cancer
Tumour
Breast cancer
Metastatic
Secondary

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on August 02, 2015