A Study Comparing AZD2014 vs Everolimus in Patients With Metastatic Renal Cancer

NCT01793636 | Terminated Phase 2 DMC

• 1 other identifier: 008424 QM
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 9

Brief 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. 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.

Conditions

Metastatic Clear Cell Renal Carcinoma

Outcome Measures

Primary Outcomes (1)

• To investigate if single agent AZD2014 delays progression free survival compared to everolimus using RESIST v1.1

  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.

  3 years

Other Outcomes (1)

• To compare overall survival of the two group of patients.

  3 years

Study Arms (2)

AZD2014

EXPERIMENTAL

AZD2014- tablets, starting dose 50mg BD everyday, until disease progression or untolerable toxicity

Drug: AZD2014

Everolimus

ACTIVE COMPARATOR

Everolimus- tablets, starting dose 10mg OD everyday until disease progression or untolerable toxicity

Drug: Everolimus

Interventions

AZD2014 DRUG

AZD2014 vs Everolimus

Also known as: Everolimus/Afinitor

AZD2014

Everolimus DRUG

comparing PFS in patients treated with AZD2014 vs Everolimus

Also known as: Afinitor

Everolimus

Eligibility Criteria

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

You may qualify if:

• 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).
• 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%

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Queen Mary University of London: lead
• AstraZeneca: collaborator
• Cancer Research UK: collaborator

Study Sites (9)

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Royal Sussex County Hospital

Brighton, BN2 5BE, United Kingdom

Location

University Hospitals Coventry & Warwickshire NHS Trust

Coventry, CV2 2DX, United Kingdom

Location

Beatson West of Scotland Cancer Center

Glasgow, G12 0YN, United Kingdom

Location

St. James' Hospital

Leeds, LS9 7TF, United Kingdom

Location

Barts Health NHS Trust

London, EC1A 6BE, United Kingdom

Location

Royal Free London Hospital

London, NW3 2QG, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Southend University Hospital NHS Foundation Trust

Westcliff-on-Sea, SS0 0RY, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

vistusertib; Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Thomas Powles

  Queen Mary University of London, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: February 14, 2013
• First Posted: February 15, 2013
• Study Start: February 1, 2013
• Primary Completion: May 1, 2014
• Study Completion: November 1, 2015
• Last Updated: June 24, 2014

Record last verified: 2014-06

Locations

GB (9)