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

NCT00900627 | Completed Phase 1 Results DMC

• 1 other identifier: D0102C00003
• Study Type: interventional
• Target: 330
• Locations: 14 countries
• Sites: 38

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.

Conditions

Neoplasms; Breast Neoplasms; Breast Cancer

Keywords

Cancer; Tumour; Breast cancer; Metastatic; Secondary

Outcome Measures

Primary Outcomes (2)

• 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

• 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

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

  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

Study Arms (2)

1

EXPERIMENTAL

AZD8931 plus Paclitaxel

Drug: AZD8931; Drug: Paclitaxel

2

PLACEBO COMPARATOR

Placebo plus Paclitaxel

Drug: Paclitaxel; Drug: Placebo

Interventions

AZD8931 DRUG

Tablet Oral bid

1

Paclitaxel DRUG

IV once weekly for 3 weeks followed by a week off (repeated cycles)

Also known as: Taxol

1; 2

Placebo DRUG

Oral bid (twice daily)

2

Eligibility Criteria

• Age: 18 Years - 150 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (38)

Research Site

Brussels (Jette), Belgium

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Leuven, Belgium

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Namur, Belgium

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Sint-Niklaas, Belgium

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São Paulo, Brazil

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Sofia, Bulgaria

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Stara Zagora, Bulgaria

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Varna, Bulgaria

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Vratsa, Bulgaria

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Halifax, Nova Scotia, Canada

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London, Ontario, Canada

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Ottawa, Ontario, Canada

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Brno, Czechia

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Jičín, Czechia

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Olomouc, Czechia

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Prague, Czechia

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Praha 4 - Krc, Czechia

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Znojmo, Czechia

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Villejuif, France

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Budapest, Hungary

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Debrecen, Hungary

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Győr, Hungary

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Szeged, Hungary

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Lido di Camaiore, Italy

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Modena, Italy

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Treviglio, Italy

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Panama City, Panama

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Lima, Peru

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Barcelona, Spain

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Madrid, Spain

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Valencia, Spain

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Uppsala, Sweden

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Chur, Switzerland

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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

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MeSH Terms

Conditions

Neoplasms; Breast Neoplasms; Neoplasm Metastasis

Interventions

AZD 8931; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

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).

Results Point of Contact

• Title: Dr Serban Ghiorghiu
• Organization: Astrazeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Dr Serban Ghiorghiu

  AstraZeneca

  STUDY DIRECTOR

• Professor Jose Baselga

  Vall d'Hebron University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2009
• First Posted: May 13, 2009
• Study Start: June 1, 2009
• Primary Completion: April 1, 2012
• Study Completion: February 1, 2015
• Last Updated: January 20, 2016
• Results First Posted: September 29, 2014

Record last verified: 2016-01

Locations

BE (4); PE (1); CA (3); SE (1); FR (1); GB (5); CH (1); BR (1); BU (4); CZ (6); HU (4); ES (3); IT (3); PA (1)