Metastatic Clear Cell Renal CarcinomaPhase 2ZEBRANCT01793636
A Study Comparing AZD2014 vs Everolimus in Patients With Metastatic Renal Cancer
A Phase 2 study testing AZD2014 and Everolimus in people with Metastatic Clear Cell Renal Carcinoma, run by Queen Mary University of London at 9 sites in United Kingdom.
Trial summary
When kidney cancer spreads beyond the kidney, it is known as metastatic kidney cancer. This is very difficult to treat and almost all patients will die of their disease within 2 years of the diagnosis. Sunitinib and other related drugs (e.g. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Clear Cell Renal Carcinoma
- What is being tested?
- AZD2014 and Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 9 sitesUnited Kingdom
- Study dates
- Feb 2013to Nov 2015
- 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
- Histopathologically confirmed renal cell carcinoma with measurable metastases on CT/MRI imaging. Only a component of clear cell is required.
- Radiological progressive disease on VEGF targeted therapy (RECIST v1.1). Exposure to more than one line of VEGF targeted therapy is acceptable. Previous treatment with initial interferon or IL-2 or other experimental agent is acceptable (with the exception of drugs specifically targeting mTOR).
- Evidence of measurable disease (ie, ≥1 malignant tumour mass that can be accurately measured in at least 1 dimension ≥ 20 mm with conventional computerized tomography [CT] scan or Magnetic Resonance Imaging [MRI], or ≥10 mm (except lymph nodes which must have short axis ≥ 15 mm) with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm). Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable.
- Adequate organ function as defined by the following criteria:
- Total serum bilirubin ≤1.5 x ULN (patients with Gilbert's disease exempt),
- Serum transaminases ≤3.0 x ULN (x5 in the presence of liver metastasis).
Show all 16Show fewer
- Serum creatinine ≤ 2 x ULN or Cockcroft and Gault >30ml/min
- Absolute neutrophil count (ANC) ≥1.5 x 109/L without growth factor support,
- Platelets ≥ 100 x 109/L
- Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment.
- Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures
- ECOG performance status of 0, 1 or 2.
- Life expectance >12 weeks
- At least 14 days since the end of prior systemic treatment (sunitinib, pazopanib, sorafenib), radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to NCI CTCAE Version 4.0 grade ≤1 or back to baseline except for alopecia or hypothyroidism. A 21 day gap between bevacizumab and interferon therapy should exist.
- Fasting blood sugar ≤8mmol/l and HbA1C ≤7%
- Age ≥18 years
Who cannot join
- Previous exposure to mTOR inhibitors for metastatic renal cancer.
- Females of child-bearing potential. The definition of child-bearing potential: women between menarche and menopause who have not been permanently or surgically sterilised and capable of procreation. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception.
- Pregnant and Breast feeding women.
- Other severe acute or chronic medical or psychiatric condition, or laboratory abnormally that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgement of the investigator, would make the patient inappropriate for entry into this study. Specifically the following indications are contraindicated: Hereditary galacto-intolerance, glucose/galactose malabsorption and lactose deficiency
- Untreated clinically symptomatic brain or meningeal metastases. Patients with evidence of clinically stable brain metastases are eligible providing that they do not require corticosteroids.
- Any evidence of severe or uncontrolled diseases e.g., unstable or uncompensated respiratory, hepatic or renal disease.
Show all 30Show fewer
- Evidence of interstitial fibrotic lung disease (bilateral, diffuse, parenchymal lung disease).
- Unresolved toxicity ≥ CTCAE v.4.0 grade 2 (except alopecia and hypothyroidism) from previous anti-cancer therapy.
- History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ or localised controlled prostate cancer) within 5 years, unless the patient has been disease free for 2 years and there is a tissue diagnosis of the primary cancer of interest from a target lesion.
- Uncontrolled diabetes mellitus or hyperlipidaemia (> grade 1)
- Treatment with an investigational drug (not including VEGF TKIs such as pazopanib/ tivozanib) within 21 days prior to the first dose of therapy. If investigational drug is a VEGF TKI then with 14 days prior to the first dose of therapy
- Patients who have experienced any of the following procedures or conditions currently or in the preceding 12 months:
- Coronary artery bypass graft
- Angioplasty
- Vascular stent
- Myocardial infarction
- Angina pectoris
- Congestive heart failure new york heart association grade ≥2
- Ventricular arrhythmias requiring continuous therapy
- Supraventricular arrhythmias including atrial fibrillation, which are uncontrolled
- Haemorrhagic or thrombotic stroke, including transient ischaemic attacks or
- Any other central nervous system bleeding
- Mean resting QTcF ≥470 msec as per local reading
- Abnormal ECHO at baseline (left ventricular ejection fraction [LVEF] <50%
- Known inherited or acquired immunodeficiency
- Known active hepatitis B or C infection or Known HIV.
- Other concomitant anti-cancer therapy (including LHRH agonists) except steroids
- Previous bone marrow transplant
- Age <18 years
- Any haemopoietic growth factors (eg, G-CSF, GM-CSF) within 2 weeks prior to receiving study drug
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United Kingdom9 sites
Royal Bournemouth Hospital
Bournemouth, BH7 7DW
Royal Sussex County Hospital
Brighton, BN2 5BE
University Hospitals Coventry & Warwickshire NHS Trust
Coventry, CV2 2DX
Beatson West of Scotland Cancer Center
Glasgow, G12 0YN
St. James' Hospital
Leeds, LS9 7TF
Barts Health NHS Trust
London, EC1A 6BE
Royal Free London Hospital
London, NW3 2QG
Southampton General Hospital
Southampton, SO16 6YD
Southend University Hospital NHS Foundation Trust
Westcliff-on-Sea, SS0 0RY
About this study
Official title: An Open Label, Randomised Phase II Study, Comparing AZD2014 Versus Everolimus With Advanced Metastatic Renal Cancer and Progression on VEGF Targeted Therapy
When kidney cancer spreads beyond the kidney, it is known as metastatic kidney cancer. This is very difficult to treat and almost all patients will die of their disease within 2 years of the diagnosis.
Sunitinib and other related drugs (e.g. pazopanib) have become standard therapy for untreated patients with metastatic kidney cancer. They target a growth factor known as VEGF which is important in treating kidney cancer. Although the results with this drug are impressive, patients develop resistance to the drug and stop therapy. It is currently standard practice is to give everolimus when resistance to sunitinib occurs; this is associated with clear clinical benefit.
However the average time to cancer regrowth with everolimus is only 5 months. It is thought this might be because, everolimus only partially inhibits its target (TORC 1 and TORC 2). Therefore further improvement in treating patients is required. AZD2014 is a promising new drug which does inhibit both TORC 1 and TORC 2 and is therefore worthy of investigation in renal cancer as it theoretically could may have advantages over everolimus. Therefore study compares AZD2014 to everolimus in the setting where everolimus is used as standard of care. (e.g. in patients who have failed drug like sunitinib). The study is a randomised trial allowing us to quantify the benefit and potential for further development of AZD2014. Repeat Xrays (CT scans) will be used to assess if the new drug delays tumour growth. Patients will be closely followed up in clinic to ensure safety. A maximum of 122 patients will be recruited into this multi centre national trial. The primary goal of the study is to investigate if AZ2014 delays the time for cancer regrowth (time to progression) compared to everolimus.
Read the detailed description
Renal cell cancer, also referred to as kidney cancer, is diagnosed in approximately 170,000 people worldwide annually, resulting in 82,000 deaths. Treatment for metastatic kidney cancer is difficult. Almost all of the patients die from their disease.
In 2006 a new drug called sunitinib, a tyrosine kinase inhibitor, transformed treatment options. It targets the development of new blood vessels within the cancer. Although the results with this drug are impressive, patients develop resistance a median after 11 months to the drug, relapse and die of renal cancer. It is currently standard practice to switch to everolimus when resistance to sunitinib occurs; this is associated with clear clinical benefit.
POTENTIAL RISKS FOR PATIENTS RECEIVING AZD2014:
The main risks and burdens to the patients participating in the study are the potential for side effects of the AZD2014 drug. The phase I study using this drug has been completed, therefore we know it is safe to administer to patients and we have a good idea of what side effects the drug causes. But as the drug is given to larger numbers, additional side effects may be discovered. The activity of the drug has not been evaluated in kidney cancer. Therefore we are not sure if AZD2014 will work
POTENTIAL RISKS FOR PATIENTS RECEIVING EVEROLIMUS:
Everolimus is the current standard therapy for these patients so the risks associated with study drug for these patients are the same as standard of care.
POTENTIAL RISKS FOR ALL PATIENTS:
SIDE EFFECTS:
Side effects will be closely monitored during and after the study. Patients are required to attend clinic weekly for the first four weeks and then every 4 weeks whilst they are on study medication where adverse events will be recorded.
The patient information sheet includes details on expected adverse events for patients to look out for and also details that unexpected events may occur. Patients are provided with the research nurse and principal investigator contact details should any adverse events occur during the course of the study.
Other medical professionals are informed that patients are receiving an experimental drug (through GP letter and labelling of hospital records). There will be an independent data monitoring committee for the trial which will closely assess the side effects of the drugs on a regular basis and the trial results to make sure there are no risk excess to patients.
- Conditions
- Metastatic Clear Cell Renal Carcinoma
- Being tested
- AZD2014, Everolimus
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD2014Drug
Also called Everolimus/Afinitor
AZD2014 vs Everolimus
EverolimusDrug
Also called Afinitor
comparing PFS in patients treated with AZD2014 vs Everolimus
| Study group | Role | What they receive |
|---|---|---|
| AZD2014 | Experimental | AZD2014- tablets, starting dose 50mg BD everyday, until disease progression or untolerable toxicity Receives: Drug: AZD2014 |
| Everolimus | Active comparator | Everolimus- tablets, starting dose 10mg OD everyday until disease progression or untolerable toxicity Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate if single agent AZD2014 delays progression free survival compared to everolimus using RESIST v1.1
Measured: Completion of study- approx 3 years
Secondary outcomes (1)
To evaluate tumour response rate after at least 8 weeks of treatment with the study drugs.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionMay 2014
- Study completionNov 2015 (estimated)
Why it stopped: Inferior efficacy of study drug in renal indication.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Clear Cell Renal CarcinomaStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe sponsor's other registered studies.
- 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
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Cancer Research UK
- Responsible party
- Principal investigator, Centre of Experimental Medicine, Queen Mary University of London
- Investigators
- Thomas Powles, Principal investigator, Queen Mary University of London, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01793636
- Sponsor's protocol ID
- 008424 QM
- Acronym
- ZEBRA
- Status last verified
- Jun 2014
- First submitted
- 14 Feb 2013
- Last updated
- 24 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Randomised Phase II Study, Comparing AZD2014 Versus Everolimus With Advanced Metastatic Renal Cancer and Progression on VEGF Targeted Therapy
- ClinicalTrials.gov ID
- NCT01793636
- Acronym / sponsor ID
- ZEBRA / 008424 QM
- Conditions
- Metastatic Clear Cell Renal Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inferior efficacy of study drug in renal indication.
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- AstraZeneca, Cancer Research UK
- Study start
- Feb 2013
- Primary completion
- May 2014 (actual)
- Study completion
- Nov 2015 (estimated)
- First posted
- 15 Feb 2013 (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.
When kidney cancer spreads beyond the kidney, it is known as metastatic kidney cancer. This is very difficult to treat and almost all patients will die of their disease within 2 years of the diagnosis.
Sunitinib and other related drugs (e.g. pazopanib) have become standard therapy for untreated patients with metastatic kidney cancer. They target a growth factor known as VEGF which is important in treating kidney cancer. Although the results with this drug are impressive, patients develop resistance to the drug and stop therapy. It is currently standard practice is to give everolimus when resistance to sunitinib occurs; this is associated with clear clinical benefit.
However the average time to cancer regrowth with everolimus is only 5 months. It is thought this might be because, everolimus only partially inhibits its target (TORC 1 and TORC 2). Therefore further improvement in treating patients is required. AZD2014 is a promising new drug which does inhibit both TORC 1 and TORC 2 and is therefore worthy of investigation in renal cancer as it theoretically could may have advantages over everolimus. Therefore study compares AZD2014 to everolimus in the setting where everolimus is used as standard of care. (e.g. in patients who have failed drug like sunitinib). The study is a randomised trial allowing us to quantify the benefit and potential for further development of AZD2014. Repeat Xrays (CT scans) will be used to assess if the new drug delays tumour growth. Patients will be closely followed up in clinic to ensure safety. A maximum of 122 patients will be recruited into this multi centre national trial. The primary goal of the study is to investigate if AZ2014 delays the time for cancer regrowth (time to progression) compared to everolimus.
Detailed description
Renal cell cancer, also referred to as kidney cancer, is diagnosed in approximately 170,000 people worldwide annually, resulting in 82,000 deaths. Treatment for metastatic kidney cancer is difficult. Almost all of the patients die from their disease.
In 2006 a new drug called sunitinib, a tyrosine kinase inhibitor, transformed treatment options. It targets the development of new blood vessels within the cancer. Although the results with this drug are impressive, patients develop resistance a median after 11 months to the drug, relapse and die of renal cancer. It is currently standard practice to switch to everolimus when resistance to sunitinib occurs; this is associated with clear clinical benefit.
POTENTIAL RISKS FOR PATIENTS RECEIVING AZD2014:
The main risks and burdens to the patients participating in the study are the potential for side effects of the AZD2014 drug. The phase I study using this drug has been completed, therefore we know it is safe to administer to patients and we have a good idea of what side effects the drug causes. But as the drug is given to larger numbers, additional side effects may be discovered. The activity of the drug has not been evaluated in kidney cancer. Therefore we are not sure if AZD2014 will work
POTENTIAL RISKS FOR PATIENTS RECEIVING EVEROLIMUS:
Everolimus is the current standard therapy for these patients so the risks associated with study drug for these patients are the same as standard of care.
POTENTIAL RISKS FOR ALL PATIENTS:
SIDE EFFECTS:
Side effects will be closely monitored during and after the study. Patients are required to attend clinic weekly for the first four weeks and then every 4 weeks whilst they are on study medication where adverse events will be recorded.
The patient information sheet includes details on expected adverse events for patients to look out for and also details that unexpected events may occur. Patients are provided with the research nurse and principal investigator contact details should any adverse events occur during the course of the study.
Other medical professionals are informed that patients are receiving an experimental drug (through GP letter and labelling of hospital records). There will be an independent data monitoring committee for the trial which will closely assess the side effects of the drugs on a regular basis and the trial results to make sure there are no risk excess to patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD2014 | Experimental | Drug: AZD2014AZD2014- tablets, starting dose 50mg BD everyday, until disease progression or untolerable toxicity |
| Everolimus | Active comparator | Drug: EverolimusEverolimus- tablets, starting dose 10mg OD everyday until disease progression or untolerable toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histopathologically confirmed renal cell carcinoma with measurable metastases on CT/MRI imaging. Only a component of clear cell is required.
- Radiological progressive disease on VEGF targeted therapy (RECIST v1.1). Exposure to more than one line of VEGF targeted therapy is acceptable. Previous treatment with initial interferon or IL-2 or other experimental agent is acceptable (with the exception of drugs specifically targeting mTOR).
- Evidence of measurable disease (ie, ≥1 malignant tumour mass that can be accurately measured in at least 1 dimension ≥ 20 mm with conventional computerized tomography [CT] scan or Magnetic Resonance Imaging [MRI], or ≥10 mm (except lymph nodes which must have short axis ≥ 15 mm) with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm). Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable.
- Adequate organ function as defined by the following criteria:
- Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment.
Key exclusion criteria (30 listed)
- Previous exposure to mTOR inhibitors for metastatic renal cancer.
- Females of child-bearing potential. The definition of child-bearing potential: women between menarche and menopause who have not been permanently or surgically sterilised and capable of procreation. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception.
- Pregnant and Breast feeding women.
- Other severe acute or chronic medical or psychiatric condition, or laboratory abnormally that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgement of the investigator, would make the patient inappropriate for entry into this study. Specifically the following indications are contraindicated: Hereditary galacto-intolerance, glucose/galactose malabsorption and lactose deficiency
- Untreated clinically symptomatic brain or meningeal metastases. Patients with evidence of clinically stable brain metastases are eligible providing that they do not require corticosteroids.
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 |
|---|---|---|
| AZD2014Also: Everolimus/AfinitorAZD2014 vs Everolimus | Drug | AZD2014 |
| EverolimusAlso: Afinitorcomparing PFS in patients treated with AZD2014 vs Everolimus | Drug | Everolimus |
Primary outcome
To investigate if single agent AZD2014 delays progression free survival compared to everolimus using RESIST v1.1
Time frame: Completion of study- approx 3 years
1 secondary outcome
To evaluate tumour response rate after at least 8 weeks of treatment with the study drugs.
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Inferior efficacy of study drug in renal indication.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2014.
- Related InfoLink provided by the sponsor.
Related trials for Metastatic Clear Cell Renal Carcinoma
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma
RecruitingPhase 1
A Study of MGC026 in Participants With Advanced Solid Tumors
Advanced Solid Tumor, Advanced Cancer
RecruitingPhase 1
Phase 1 Study Evaluating the Safety and PK of ADU-1805 in Advanced Solid Tumors
Solid Tumor, Adult, Metastatic Solid Tumor
Active, not recruitingPhase 2
Upfront Immune Checkpoint Inhibitors With Deferred Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma
Immune Checkpoint Inhibitors, Cytoreductive Nephrectomy
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.
Thomas Powles principal investigator
Queen Mary University of London, UK
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD2014 and Everolimus in people with Metastatic Clear Cell Renal Carcinoma, run by Queen Mary University of London at 9 sites 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 16 inclusion and 30 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: stopped early, as of the sponsor's last update on 24 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites 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 stopped early (reason given: Inferior efficacy of study drug in renal indication.). Results are not available in the source record.
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?
To investigate if single agent AZD2014 delays progression free survival compared to everolimus using RESIST v1.1 (time frame: Completion of study- approx 3 years). 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 24 Jun 2014.