A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC)

Inclusion criteria

• Provision of informed consent prior to any study specific procedures, sampling and analyses.
• Histologically confirmed PRCC, which is locally advanced or metastatic.
• Availability of an archival tumor sample or a pre-treatment fresh tumor sample for confirmation of PRCC by a central laboratory and other biomarker
• Treatment naïve or have failed on previous treatment for PRCC. Previous treatments may include: targeted therapy (i.e. sunitinib, sorafenib, bevacizumab, pazopanib, temsirolimus, and everolimus), traditional immunotherapy (i.e. interferon-a, Interleukin-2), chemotherapy or a combination of chemoimmunotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• At least one lesion, not previously irradiated, and not chosen for a biopsy if performed during the screening period that can be accurately measured at baseline and which is suitable for accurate repeated measurements.
• Adequate hematological function defined as:
• Absolute neutrophil count ≥1500/μL
• Haemoglobin ≥9 g/dL
• Platelets ≥100,000/μL
• Adequate liver function defined as:
• Alanine aminotransferase and aspartate aminotransferase ≤2.5 x the upper limit of normal (ULN)
• Total bilirubin ≤1.5 x ULN
• Adequate renal function defined as glomerular filtration rate ≥ 40 mL/min,
• Adequate coagulation parameters, defined as International Normalisation Ratio 160 mmHg or diastolic blood pressure >100 mmHg) (patients with values above these levels must have their blood pressure controlled with medication prior to starting treatment).
• Mean resting correct QT interval (QTc) >470 msec obtained from triplicate electrocardiagrams
• Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograms, e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital or familial long QT syndrome or family history of unexplained sudden death under 40 years of age or any concomitant medications known to prolong QT interval.
• Currently receiving treatment with therapeutic doses of warfarin sodium. Low molecular weight heparin is allowed.
• Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
• Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C.
• Presence of other active cancers, or history of treatment for invasive cancer ≤5years. Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.