Carboplatin With or Without ZD4054 in Patients With Metastatic Breast Cancer

NCT01134497 | Withdrawn Phase 2 DMC

• 2 other identifiers: SPON-804-102010-018837-23
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

In this "randomised Phase II trial" all patients will receive carboplatin, with half randomly selected to receive ZD4054. The other half to also receive a dummy pill or placebo, this is so that we can accurately assess how much extra benefit ZD4054 may give. The trial will recruit 132 patients with metastatic breast cancer from across the UK and assess whether adding ZD4054 to carboplatin delays progression of their disease. It will also show whether the side effects of adding ZD4054 to carboplatin chemotherapy are acceptable. Because ZD4054 has not previously been given with carboplatin to this population, in Stage 1 of the study 6 patients will receive ZD4054 with carboplatin. If there are no untoward side effects with carboplatin and ZD4054 then the trial will proceed to Stage 2 and a further 126 patients will be randomised to receive carboplatin with either ZD4054 or the placebo; neither the patient nor their doctor will know whether she is receiving ZD4054 or placebo.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• PFS (time to event)

  PFS (time to event) based on Response Evaluation Criteria in Solid Tumours (RECIST v1.1). Time from enrolment to any progression and/or death. Those progression-free and alive will be censored at time of last follow-up visit.

  18 weeks of treatment

Secondary Outcomes (3)

• Safety

  52 weeks

• Tolerability

  52 weeks

• Feasibility

  18 weeks

Study Arms (2)

Arm A (control): carboplatin + placebo

ACTIVE COMPARATOR

The control arm will consist of up to 6 cycles of carboplatin (AUC5 q21d for 6 cycles) iv over 30 minutes on day 1, plus placebo by mouth on days 1-21 of a 21 day cycle.

Drug: Placebo

Arm B: carboplatin + ZD4054

EXPERIMENTAL

The experimental arm will consist of up to 6 cycles of carboplatin (AUC5 q21d for 6 cycles) iv over 30 minutes on day 1, plus ZD4054 (10mg daily) od by mouth on days 1-21 of a 21 day cycle.

Drug: ZD4054

Interventions

Placebo DRUG

The control arm will consist of up to 6 cycles of carboplatin (AUC5 q21d for 6 cycles) iv over 30 minutes on day 1, plus placebo by mouth on days 1-21 of a 21 day cycle

Arm A (control): carboplatin + placebo

ZD4054 DRUG

The experimental arm will consist of up to 6 cycles of carboplatin (AUC5 q21d for 6 cycles) iv over 30 minutes on day 1, plus ZD4054 (10mg daily) od by mouth on days 1-21 of a 21 day cycle.

Also known as: Zibotentan

Arm B: carboplatin + ZD4054

Eligibility Criteria

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

You may qualify if:

• Patients aged over 18
• Histological or cytological diagnosis of metastatic breast cancer, or previous histological diagnosis of breast cancer and evidence of metastatic or locally advanced disease unsuitable for local therapy
• No more than 2 prior lines of chemotherapy treatment for metastatic breast cancer
• Life expectancy greater than 12 weeks
• Patients must have previously received or be ineligible for a taxane
• Informed written consent
• Adequate bone marrow and hepatic function
• Haemoglobin ≥ 9.0 g/dl (if no prior transfusion or transfusion more than 4 weeks previously) or ≥ 10.0 g/dl (transfusion within last 4 weeks), absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥100 x 109/L
• Total bilirubin \< 1.5 x upper normal limit
• AST and ALT ≤ 2.5 x upper normal limit (or ≤ 5x UNL in the presence of liver metastases)
• Adequate renal function
• GFR ≥ 60 mls/min calculated using Wright Formula or measured by EDTA plasma clearance At least one measurable lesion on CT scanning. Disease measurable by other RECIST v1.1 compatible imaging (e.g. MRI, CXR) or clinically measurable will be allowed as long as the same assessment method is used throughout the trial
• ECOG performance status ≤ 2

You may not qualify if:

• Previous treatment with platinum based chemotherapy
• Known brain or leptomeningeal metastases
• Any co-existing medical conditions that, in the Investigator's judgement, may substantially increase the risk associated with the patient's participation in the study or potentially hamper compliance with the study protocol and follow-up schedule
• Concomitant medication unsuitable for combination with trial medication
• Concomitant administration of potent CYP3A inhibitors, specifically: Protease inhibitors (atanazavir, indinavir, nelfinavir, ritonavir, saquinavir), Macrolide antibiotics (clarithromycin, telithromycin), Azole antifungals (ketoconazole, itraconazole, voriconazole), nefazodone

Sponsors & Collaborators

• Cardiff University: lead

Study Sites (1)

Wales Cancer Trials Unit

Cardiff, CF14 4YS, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ZD4054

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2010
• First Posted: June 2, 2010
• Primary Completion: August 16, 2011
• Study Completion: August 16, 2011
• Last Updated: May 22, 2018

Record last verified: 2018-05

Locations

GB (1)