Metastatic Breast CancerPhase 2PLANETNCT01134497
Carboplatin With or Without ZD4054 in Patients With Metastatic Breast Cancer
A Phase 2 study testing ZD4054 in people with Metastatic Breast Cancer, run by Cardiff University at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- ZD4054
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Start not givento 16 Aug 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised Phase II Study of Carboplatin With or Without the Addition of the ETAR Inhibitor ZD4054 as Treatment for Patients With Metastatic Breast Cancer
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.
Read the detailed description
In the UK about 41,000 patients are diagnosed with breast cancer each year. More and more patients are surviving breast cancer, mostly due to the earlier detection and improvements in treatment. Nevertheless, in about 6% of patients the cancer has already spread to other parts of the body when they are first diagnosed; in a further 30% of patients the cancer comes back elsewhere in their body after initial treatment. Once it has spread to other parts of the body, breast cancer is incurable, with patients living, on average, a further 24 months. The aims when treating patients with metastatic breast cancer are to prolong and improve their day to day life. A number of different chemotherapy drugs are available for treatment of metastatic breast cancer. There is, however, still a need to develop new treatments. The aim of this trial is to use a new drug called ZD4054 combined with an established chemotherapy drug (carboplatin) to see whether this prolongs the period for which patients live with the cancer kept under control.
ZD4054 is a new, oral drug which may help to slow down cancer growth. It works by blocking growth that is controlled by specific proteins on cancer cells called endothelins.
Endothelins act by binding to their endothelin receptors, presence of these receptors have been found in about 45% of breast cancer cases. ZD4054 is an endothelin receptor blocker. We hope to show that adding this new drug increases the effectiveness of carboplatin. We know from trials in other cancers that similar drugs may be able to slow down the growth of tumours.
Metastatic breast cancer (MBC) remains incurable and there has been little change in long term outcomes. Chemotherapy is used to improve symptoms and prolong survival in patients with advanced breast cancer. Nevertheless, most tumours inevitably progress and the clinical response rates to subsequent chemotherapy agents are disappointing. There is, therefore, a need for continued clinical research into new strategies to enhance the effectiveness of currently available chemotherapy agents to improve survival.
The endothelin pathway has been implicated in a number of oncogenic pathways. ET-1 and ETAR are frequently over-expressed in breast cancers and are prognostic for poor outcome. Inhibition of the endothelin pathway enhances cytotoxicity when combined with chemotherapy agents such as carboplatin in pre-clinical models. ZD4054 is a specific inhibitor of ETAR and represents a novel therapeutic target in breast cancer.
This study investigates whether ZD4054, an oral endothelin A receptor (ETAR) inhibitor, in combination with carboplatin chemotherapy, has sufficient activity to warrant a future Phase III trial in patients with advanced/metastatic breast cancer.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Placebo, ZD4054
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
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
ZD4054Drug
Also called Zibotentan
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: ZD4054 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 weeks of treatment
Secondary outcomes (3)
Safety
Safety will be assesssed throughout the trial treatment and during follow-up.
Measured: 52 weeks
Tolerability
Side effects/tolerability will be assesssed throughout the trial treatment and during follow-up. Participants will have the option of continuing ZD4054 even after the 18 week treatment period has been completed. This will be at the discretion of the consultant.
Measured: 52 weeks
Feasibility
The trial will also assess number of participants requiring dose delays or reductions and / or treatment withdrawal
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2010 (estimated)
- Primary completion16 Aug 2011 (estimated)
- Study completion16 Aug 2011
Why it stopped: New information on IMP affected the cost/benefit ratio
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cardiff University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01134497
- Sponsor's protocol ID
- SPON-804-10
- Other IDs
- 2010-018837-23
- Acronym
- PLANET
- Status last verified
- May 2018
- First submitted
- 27 May 2010
- Last updated
- 22 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Phase II Study of Carboplatin With or Without the Addition of the ETAR Inhibitor ZD4054 as Treatment for Patients With Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT01134497
- Acronym / sponsor ID
- PLANET / SPON-804-10
- Conditions
- Metastatic Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: New information on IMP affected the cost/benefit ratio
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Cardiff UniversityUniversity, hospital or other
- Primary completion
- 16 Aug 2011 (estimated)
- Study completion
- 16 Aug 2011 (actual)
- First posted
- 2 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In the UK about 41,000 patients are diagnosed with breast cancer each year. More and more patients are surviving breast cancer, mostly due to the earlier detection and improvements in treatment. Nevertheless, in about 6% of patients the cancer has already spread to other parts of the body when they are first diagnosed; in a further 30% of patients the cancer comes back elsewhere in their body after initial treatment. Once it has spread to other parts of the body, breast cancer is incurable, with patients living, on average, a further 24 months. The aims when treating patients with metastatic breast cancer are to prolong and improve their day to day life. A number of different chemotherapy drugs are available for treatment of metastatic breast cancer. There is, however, still a need to develop new treatments. The aim of this trial is to use a new drug called ZD4054 combined with an established chemotherapy drug (carboplatin) to see whether this prolongs the period for which patients live with the cancer kept under control.
ZD4054 is a new, oral drug which may help to slow down cancer growth. It works by blocking growth that is controlled by specific proteins on cancer cells called endothelins.
Endothelins act by binding to their endothelin receptors, presence of these receptors have been found in about 45% of breast cancer cases. ZD4054 is an endothelin receptor blocker. We hope to show that adding this new drug increases the effectiveness of carboplatin. We know from trials in other cancers that similar drugs may be able to slow down the growth of tumours.
Metastatic breast cancer (MBC) remains incurable and there has been little change in long term outcomes. Chemotherapy is used to improve symptoms and prolong survival in patients with advanced breast cancer. Nevertheless, most tumours inevitably progress and the clinical response rates to subsequent chemotherapy agents are disappointing. There is, therefore, a need for continued clinical research into new strategies to enhance the effectiveness of currently available chemotherapy agents to improve survival.
The endothelin pathway has been implicated in a number of oncogenic pathways. ET-1 and ETAR are frequently over-expressed in breast cancers and are prognostic for poor outcome. Inhibition of the endothelin pathway enhances cytotoxicity when combined with chemotherapy agents such as carboplatin in pre-clinical models. ZD4054 is a specific inhibitor of ETAR and represents a novel therapeutic target in breast cancer.
This study investigates whether ZD4054, an oral endothelin A receptor (ETAR) inhibitor, in combination with carboplatin chemotherapy, has sufficient activity to warrant a future Phase III trial in patients with advanced/metastatic breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (control): carboplatin + placebo | Active comparator | Drug: PlaceboThe 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 B: carboplatin + ZD4054 | Experimental | Drug: ZD4054The 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboThe 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 | Arm A (control): carboplatin + placebo |
| ZD4054Also: ZibotentanThe 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 | Arm B: carboplatin + ZD4054 |
Primary outcome
PFS (time to event)
Time frame: 18 weeks of treatment
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.
3 secondary outcomes
Safety
Time frame: 52 weeks
Tolerability
Time frame: 52 weeks
Feasibility
Time frame: 18 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ZD4054 in people with Metastatic Breast Cancer, run by Cardiff University at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time to event) (time frame: 18 weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2018; AzTrials last refreshed its copy on 8 Nov 2026.