BEZ235 in Patients With Advanced Renal Cell Carcinoma (RCC)

Stopped early · Phase 1/Phase 2

Conditions studied: Renal Cancer

In brief

This study tests a new medication for treatment of kidney cancer, called BEZ235. This medication works by blocking several mechanisms that the cancer needs to grow and survive. By blocking these mechanisms, the medication can thus suppress further growth of the cancer, possibly kill cancer cells. Older kidney cancer medications (such as temsirolimus \[Torisel®\] or everolimus \[Afinitor®\]) typically only block one mechanism in cancer cells, so the investigators think that BEZ235 may work even better against kidney cancer. The purpose of the first part of this study is to test the safety of giving BEZ235 at different doses. The investigators are trying to find a safe dose of BEZ235 and want to find out what effects, good and/or bad, it has on the patient and the cancer.

Key facts

Study ID

NCT01453595

Run by

Memorial Sloan Kettering Cancer Center

People needed

10

Starts

2011-10-01

Expected to finish

2014-04-01

Last updated by the study team

2016-02-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Advanced renal cell carcinoma. Advanced disease is defined as unresectable, locally recurrent disease or metastatic disease. This must by confirmed by MSKCC pathology review with the following requirements:
• Phase 1b: Any histologic subtype of RCC.
• Phase 2: clear cell type RCC or predominant clear cell component.
• Patients will be screened for prior systemic therapies:
• Phase 1b: Any prior therapy.
• Phase 2: Progression of disease on at least one prior treatment with an mTOR inhibitor (such as everolimus, temsirolimus, ridaforolimus). Other prior systemic therapies including VEGF directed therapy (e.g. sunitinib, sorafenib, bevacizumab) and immunotherapy (e.g. IL-2, interferon-α) are also permitted. Evidence of unidimensionally measurable disease per RECIST 1.1 (Eisenhauer, Therasse et al. 2009).
• Resolution of all acute toxic effects of prior systemic treatments, radiotherapy or surgical procedures to NCI CTCAE Version 4.0 grade ≤1.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, which is not declining during the last 2 weeks.
• 18 years of age or older.
• Adequate organ function as defined by the following criteria:
• Absolute neutrophil count (ANC) ≥1,000/μL
• Platelets ≥100,000/μL
• Hemoglobin ≥9.0 g/dL
• Serum calcium ≤12.0 mg/dL
• Serum creatinine ≤1.5 x upper limit of normal (ULN); if this is exceeded, estimated creatinine clearance must be ≥ 30 ml/min
• Total serum bilirubin ≤ 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin of ≤ 3 x ULN, with direct bilirubin ≤ 1.5 x ULN)
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT)
• ≤3 x ULN (≤5 x ULN in the setting of hepatic metastases)
• INR ≤ 2. (Anticoagulation with warfarin is contraindicated)
• Fasting plasma glucose (FPG) ≤ 140mg/dL
• HgbA1c ≤ 8%
• Fasting serum cholesterol ≤300 mg/dL, fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to undergoing study screening procedures.
• Subject's willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if…

• Patients who have received prior treatment with a P13K inhibitor (Phase 2 portion only).
• Patients within 28 days post major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) or significant traumatic injury.
• Patients who had radiation therapy within 28 days prior to start of study treatment (palliative radiotherapy to bone lesions allowed if completed 2 weeks prior to study treatment start).
• Patients who have received chemotherapy, immunotherapy or other investigational agents ≤ 2 weeks prior to study treatment start.
• Patients currently receiving medications known to be inducers or moderate / strong inhibitors of CYP3A4 (see table 9.2 for a list) Patients must discontinue such medications ≥ 7 days prior to initiation of study treatment.
• Patients currently receiving medications with a significant risk to induce Torsades de Pointes
• Patients who are currently receiving treatment with warfarin sodium (Coumadin®). If treatment is discontinued or switched to an alternate anticoagulant prior to enrollment, INR within ≤48h prior to study initiation has to return to ≤ 2 x ULN.
• Patients receiving chronic treatment with systemic corticosteroids or other immunosuppressive agents (inhaled or topical steroids are allowed)
• Patients with evidence or history of central nervous system (CNS) metastases or spinal cord compression, unless prior treatment with surgery or radiotherapy AND no progression of CNS disease within 6 months prior to enrollment. Patients must not be receiving chronic corticosteroid therapy for CNS metastases.
• Patients who have a history of severe medical conditions or other conditions that could affect their participation in the study such as:
• symptomatic intrinsic lung disease requiring oxygen supplementation at baseline
• uncontrolled hypertension (i.e., SBP>180 mmHg or DBP >100mmHg)
• any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study
• liver disease such as cirrhosis or decompensated liver disease.
• Impairment of gastrointestinal function that may impair absorption of BEZ235 (e.g. ulcerative diseases, uncontrolled nausea/vomiting; diarrhea ≥ grade 2; malabsorption syndromes after prior small-bowel resection)
• Immunocompromised patients and/or history of HIV seropositivity
• Patients with prior or current cardiac problems including:
• History of unstable angina pectoris (at any time), symptomatic congestive heart failure (NYHA III, IV) (at any time), serious uncontrolled cardiac arrhythmia (at any time), myocardial infarction or cerebrovascular accidents ≤ 6 months prior to first study treatment or history of left ventricular dysfunction
• reduced left ventricular ejection fraction (LVEF) of <50% on screening with echocardiogram or multiple gates acquisition (MUGA) scan
• severe valvulopathies with documented compromise in cardiac function
• Any of the following on screening ECG:
• QTc interval > 480 msec (or family history of congenital QTc prolongation)
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Complete left bundle branch block
• Any conduction abnormality requiring pacemaker

Where it is running

• Memorial Sloan Kettering Cancer Center — New York, New York, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.