ZD4054 (Zibotentan) or Placebo Plus Chemotherapy in Patients With Advanced Ovarian Cancer
Sponsor
AstraZeneca (Industry)
Overall Status
Terminated
CT.gov ID
NCT00929162
Collaborator
ISTITUTO REGINA ELENA - CENTRO RICERCHE SPERIMENTALI (Other)
120
20
2
24
6
0.3
Study Details
Study Description
Brief Summary
The purpose of this study is to compare progression-free survival in patients with advanced ovarian cancer treated with ZD4054 in combination with carboplatin+paclitaxel versus placebo in combination with carboplatin+paclitaxel.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase II, Double-blind, Placebo-controlled, Multi-centre, Randomised Study of ZD4054 (Zibotentan) Plus Carboplatin and Paclitaxel or Placebo Plus Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer Sensitive to Platinum-based Chemotherapy
Study Start Date
:
Jun 1, 2009
Actual Primary Completion Date
:
Jun 1, 2011
Actual Study Completion Date
:
Jun 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ZD4054 + paclitaxel + carboplatin ZD4054 10mg oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks |
Drug: ZD4054 Zibotentan
10 mg oral tablets once daily
Drug: Paclitaxel
175mg/m2 IV on day 1 every 3 weeks
Drug: Carboplatin
Carboplatin AUC of 5.0 IV on day 1 every 3 weeks
|
| Placebo Comparator: Placebo + paclitaxel + carboplatin Placebo oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks |
Drug: Paclitaxel
175mg/m2 IV on day 1 every 3 weeks
Drug: Carboplatin
Carboplatin AUC of 5.0 IV on day 1 every 3 weeks
Drug: Placebo
matching placebo for ZD4054 10 mg
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival [Patients were followed for progression up to 2 years]
Median time (in months) from randomisation until clinical progression of disease using the Kaplan-Meier method.
Secondary Outcome Measures
- Overall Survival [Patients were followed for survival up to 2 years]
Median time (in months) from randomisation until death using the Kaplan-Meier method.
- Tumour Response Rate [While receiving paclitaxel + carboplatin study visits were aliged with its administration ie every 3 weeks, then every 6 weeks (up to 2 years)]
Objective response rate defined as participants with a complete or partial response according to RECIST
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically proven diagnosis of: - Epithelial ovarian carcinoma - Fallopian tube carcinoma - Primary serous peritoneal carcinoma
-
Radiologically documented measurable disease according to RECIST criteria assessed by Computerised Tomography (CT) or Magnetic Resonance Imaging MRI) or radiologically documented non-measurable (but evaluable) disease.
-
Advanced disease not amenable to curative surgery or radiotherapy at the time of study entry with evidence of disease recurrence or progression at least 6 months following treatment cessation of first-line platinum- containing therapy
Exclusion Criteria:
-
Clinical evidence of central nervous system (CNS) metastases
-
Non-epithelial ovarian cancer, including malignant mixed Mullerian tumours and mucinous carcinoma of the peritoneum
-
Tumour of borderline malignancy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Berlin | Germany | ||
| 2 | Research Site | Dresden | Germany | ||
| 3 | Research Site | Dusseldorf | Germany | ||
| 4 | Research Site | Essen | Germany | ||
| 5 | Research Site | Karlsruhe | Germany | ||
| 6 | Research Site | Kassel | Germany | ||
| 7 | Research Site | Kiel | Germany | ||
| 8 | Research Site | Lich | Germany | ||
| 9 | Research Site | Magdeburg | Germany | ||
| 10 | Research Site | Marburg | Germany | ||
| 11 | Research Site | Munchen | Germany | ||
| 12 | Research Site | Rostock | Germany | ||
| 13 | Research Site | Wiesbaden | Germany | ||
| 14 | Research Site | Milano | MI | Italy | |
| 15 | Research Site | Perugia | PG | Italy | |
| 16 | Research Site | Aviano | PN | Italy | |
| 17 | Research Site | Campobasso | Italy | ||
| 18 | Research Site | Modena | Italy | ||
| 19 | Research Site | Napoli | Italy | ||
| 20 | Research Site | Roma | Italy |
Sponsors and Collaborators
- AstraZeneca
- ISTITUTO REGINA ELENA - CENTRO RICERCHE SPERIMENTALI
Investigators
- Study Director: Tom Morris, AstraZeneca, Alderley Park
- Study Chair: Ian Thomas, AstraZeneca, Alderley Park
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00929162
Other Study ID Numbers:
- D4320C00036
First Posted:
Jun 26, 2009
Last Update Posted:
Aug 7, 2012
Last Verified:
Aug 1, 2012
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 132 patients with advanced ovarian cancer sensitive to platinum-based chemotherapy were recruited between 26th June 2009 and 1st June 2011. |
|---|---|
| Pre-assignment Detail | 12 of the 132 enrolled patients were not randomised to treatment groups as they failed screening |
| Arm/Group Title | ZD4054+Paclitaxel+Carboplatin | Placebo+Paclitaxel+Carboplatin |
|---|---|---|
| Arm/Group Description | ZD4054 10mg oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks | Placebo oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks |
| Period Title: Overall Study | ||
| STARTED | 59 | 61 |
| Patients Who Received Treatment | 58 | 58 |
| COMPLETED | 11 | 19 |
| NOT COMPLETED | 48 | 42 |
Baseline Characteristics
| Arm/Group Title | ZD4054+Paclitaxel+Carboplatin | Placebo+Paclitaxel+Carboplatin | Total |
|---|---|---|---|
| Arm/Group Description | ZD4054 10mg oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks | Placebo oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks | Total of all reporting groups |
| Overall Participants | 59 | 61 | 120 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Overall |
57.4
(11.98)
|
56.6
(11.07)
|
57.0
(11.49)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
59
100%
|
61
100%
|
120
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Progression Free Survival |
|---|---|
| Description | Median time (in months) from randomisation until clinical progression of disease using the Kaplan-Meier method. |
| Time Frame | Patients were followed for progression up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ZD4054+Paclitaxel+Carboplatin | Placebo+Paclitaxel+Carboplatin |
|---|---|---|
| Arm/Group Description | ZD4054 10mg oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks | Placebo oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks |
| Measure Participants | 59 | 61 |
| Median (Inter-Quartile Range) [Months] |
7.6
|
10.0
|
| Title | Overall Survival |
|---|---|
| Description | Median time (in months) from randomisation until death using the Kaplan-Meier method. |
| Time Frame | Patients were followed for survival up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall Survival was not analysed as the study was terminated early. |
| Arm/Group Title | ZD4054+Paclitaxel+Carboplatin | Placebo+Paclitaxel+Carboplatin |
|---|---|---|
| Arm/Group Description | ZD4054 10mg oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks | Placebo oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks |
| Measure Participants | 0 | 0 |
| Title | Tumour Response Rate |
|---|---|
| Description | Objective response rate defined as participants with a complete or partial response according to RECIST |
| Time Frame | While receiving paclitaxel + carboplatin study visits were aliged with its administration ie every 3 weeks, then every 6 weeks (up to 2 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of participants for analysis corresponds to patients with measurable disease at study entry |
| Arm/Group Title | ZD4054+Paclitaxel+Carboplatin | Placebo+Paclitaxel+Carboplatin |
|---|---|---|
| Arm/Group Description | ZD4054 10mg oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks | Placebo oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks |
| Measure Participants | 55 | 58 |
| Number [Participants] |
21
35.6%
|
34
55.7%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | ZD4054+Paclitaxel+Carboplatin | Placebo+Paclitaxel+Carboplatin | ||
| Arm/Group Description | ZD4054 10mg oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks | Placebo oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks | ||
All Cause Mortality |
||||
| ZD4054+Paclitaxel+Carboplatin | Placebo+Paclitaxel+Carboplatin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| ZD4054+Paclitaxel+Carboplatin | Placebo+Paclitaxel+Carboplatin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/58 (32.8%) | 13/58 (22.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/58 (1.7%) | 0/58 (0%) | ||
| Cardiac disorders | ||||
| Coronary Artery Occlusion | 0/58 (0%) | 1/58 (1.7%) | ||
| Ischaemic Cardiomyopathy | 0/58 (0%) | 1/58 (1.7%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Pain | 4/58 (6.9%) | 1/58 (1.7%) | ||
| Subileus | 4/58 (6.9%) | 0/58 (0%) | ||
| Ileus | 3/58 (5.2%) | 0/58 (0%) | ||
| Constipation | 2/58 (3.4%) | 1/58 (1.7%) | ||
| Ascites | 1/58 (1.7%) | 1/58 (1.7%) | ||
| Diarrhoea | 0/58 (0%) | 1/58 (1.7%) | ||
| Gastrointestinal Toxicity | 0/58 (0%) | 1/58 (1.7%) | ||
| Intestinal Perforation | 0/58 (0%) | 1/58 (1.7%) | ||
| Nausea | 1/58 (1.7%) | 1/58 (1.7%) | ||
| Vomiting | 0/58 (0%) | 1/58 (1.7%) | ||
| General disorders | ||||
| Pyrexia | 0/58 (0%) | 2/58 (3.4%) | ||
| General Physical Health Deterioration | 1/58 (1.7%) | 1/58 (1.7%) | ||
| Immune system disorders | ||||
| Drug Hypersensitivity | 5/58 (8.6%) | 4/58 (6.9%) | ||
| Infections and infestations | ||||
| Escherichia Infection | 0/58 (0%) | 1/58 (1.7%) | ||
| Wound Infection | 1/58 (1.7%) | 0/58 (0%) | ||
| Haemoglobin Decreased | 0/58 (0%) | 1/58 (1.7%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Ovarian Cancer Recurrent | 1/58 (1.7%) | 0/58 (0%) | ||
| Salivary Gland Neoplasm | 0/58 (0%) | 1/58 (1.7%) | ||
| Psychiatric disorders | ||||
| Insomnia | 1/58 (1.7%) | 0/58 (0%) | ||
| Reproductive system and breast disorders | ||||
| Female Genital Tract Fistula | 1/58 (1.7%) | 0/58 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pleural Effusion | 1/58 (1.7%) | 0/58 (0%) | ||
| Pulmonary Embolism | 1/58 (1.7%) | 0/58 (0%) | ||
| Vascular disorders | ||||
| Thrombosis | 1/58 (1.7%) | 0/58 (0%) | ||
| Vena Cava Thrombosis | 1/58 (1.7%) | 0/58 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| ZD4054+Paclitaxel+Carboplatin | Placebo+Paclitaxel+Carboplatin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 57/58 (98.3%) | 58/58 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 30/58 (51.7%) | 25/58 (43.1%) | ||
| Neutropenia | 26/58 (44.8%) | 22/58 (37.9%) | ||
| Leukopenia | 20/58 (34.5%) | 15/58 (25.9%) | ||
| Thrombocytopenia | 11/58 (19%) | 11/58 (19%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 2/58 (3.4%) | 4/58 (6.9%) | ||
| Eye disorders | ||||
| Lacrimation Increased | 3/58 (5.2%) | 1/58 (1.7%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 28/58 (48.3%) | 31/58 (53.4%) | ||
| Constipation | 24/58 (41.4%) | 19/58 (32.8%) | ||
| Vomiting | 21/58 (36.2%) | 20/58 (34.5%) | ||
| Abdominal Pain | 16/58 (27.6%) | 20/58 (34.5%) | ||
| Abdominal Pain Upper | 8/58 (13.8%) | 12/58 (20.7%) | ||
| Diarrhoea | 10/58 (17.2%) | 12/58 (20.7%) | ||
| Stomatitis | 7/58 (12.1%) | 9/58 (15.5%) | ||
| Dyspepsia | 1/58 (1.7%) | 4/58 (6.9%) | ||
| General disorders | ||||
| Fatigue | 20/58 (34.5%) | 27/58 (46.6%) | ||
| Asthenia | 11/58 (19%) | 17/58 (29.3%) | ||
| Oedema Peripheral | 13/58 (22.4%) | 5/58 (8.6%) | ||
| Mucosal Inflammation | 9/58 (15.5%) | 3/58 (5.2%) | ||
| Pyrexia | 9/58 (15.5%) | 7/58 (12.1%) | ||
| Oedema | 3/58 (5.2%) | 0/58 (0%) | ||
| Immune system disorders | ||||
| Drug Hypersensitivity | 15/58 (25.9%) | 10/58 (17.2%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 1/58 (1.7%) | 9/58 (15.5%) | ||
| Influenza | 4/58 (6.9%) | 5/58 (8.6%) | ||
| Metabolism and nutrition disorders | ||||
| Hypokalaemia | 7/58 (12.1%) | 2/58 (3.4%) | ||
| Decreased Appetite | 5/58 (8.6%) | 6/58 (10.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 6/58 (10.3%) | 19/58 (32.8%) | ||
| Myalgia | 6/58 (10.3%) | 12/58 (20.7%) | ||
| Back Pain | 2/58 (3.4%) | 8/58 (13.8%) | ||
| Pain In Extremity | 3/58 (5.2%) | 6/58 (10.3%) | ||
| Bone Pain | 5/58 (8.6%) | 2/58 (3.4%) | ||
| Musculoskeletal Pain | 4/58 (6.9%) | 2/58 (3.4%) | ||
| Nervous system disorders | ||||
| Headache | 27/58 (46.6%) | 17/58 (29.3%) | ||
| Paraesthesia | 11/58 (19%) | 16/58 (27.6%) | ||
| Peripheral Sensory Neuropathy | 10/58 (17.2%) | 13/58 (22.4%) | ||
| Polyneuropathy | 2/58 (3.4%) | 9/58 (15.5%) | ||
| Dysgeusia | 4/58 (6.9%) | 8/58 (13.8%) | ||
| Neuropathy Peripheral | 6/58 (10.3%) | 4/58 (6.9%) | ||
| Psychiatric disorders | ||||
| Insomnia | 3/58 (5.2%) | 5/58 (8.6%) | ||
| Depression | 3/58 (5.2%) | 0/58 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 10/58 (17.2%) | 6/58 (10.3%) | ||
| Cough | 3/58 (5.2%) | 7/58 (12.1%) | ||
| Nasal Congestion | 4/58 (6.9%) | 1/58 (1.7%) | ||
| Rhinorrhoea | 3/58 (5.2%) | 1/58 (1.7%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 28/58 (48.3%) | 28/58 (48.3%) | ||
| Pruritus | 4/58 (6.9%) | 10/58 (17.2%) | ||
| Dry Skin | 6/58 (10.3%) | 2/58 (3.4%) | ||
| Erythema | 5/58 (8.6%) | 6/58 (10.3%) | ||
| Palmar-Plantar Erythrodysaesthesia Syndrome | 2/58 (3.4%) | 4/58 (6.9%) | ||
| Rash | 3/58 (5.2%) | 2/58 (3.4%) | ||
| Vascular disorders | ||||
| Hot Flush | 1/58 (1.7%) | 4/58 (6.9%) | ||
| Hypertension | 1/58 (1.7%) | 4/58 (6.9%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AstraZeneca can review results communications prior to public release and may within 60 days of receipt require amendments to be made. AstraZeneca can also require that submission or disclosure be delayed to allow for the filing of a patent application.
Results Point of Contact
| Name/Title | Gerard Lynch |
|---|---|
| Organization | AstraZeneca |
| Phone | |
| aztrial_results_posting@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00929162
Other Study ID Numbers:
- D4320C00036
First Posted:
Jun 26, 2009
Last Update Posted:
Aug 7, 2012
Last Verified:
Aug 1, 2012