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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 330
- Locations
- 1
- Primary Endpoint
- Phase I: The Number of Dose Limiting Toxicities in AZD8931 in Combination With Weekly Paclitaxel
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 150 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
1
AZD8931 plus Paclitaxel
Intervention: AZD8931 (Drug)
1
AZD8931 plus Paclitaxel
Intervention: Paclitaxel (Drug)
2
Placebo plus Paclitaxel
Intervention: Paclitaxel (Drug)
2
Placebo plus Paclitaxel
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- Phase II: Objective Tumour Response Rate (ORR) Was Compared in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone(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(Weekly visits for routine safety monitoring, accessed up to data cut off on 11th April 2012)