Clinical trial: Cediranib as Palliative Treatment in Patients With Symptomatic Malignant Ascites or Pleural Effusion (NCT01262612)

Eligibility criteria:
Inclusion Criteria:

          -  Symptomatic malignant ascites and/or pleural effusion (from a histological proven
             solid malignancy which is refractory to standard anti-tumour therapy of for which no
             standard therapy exists)

          -  Karnofsky score ≥ 50 if the low performance score is due to ascites and/or pleural
             effusion, otherwise ≥ 60

          -  Age ≥ 18 years

          -  Written informed consent

        Exclusion Criteria:

        Contraindications for treatment with cediranib:

          -  The presence of a pleural or peritoneal tap

          -  Untreated unstable brain or meningeal metastases.

          -  Previous treatment with chemotherapeutic agents or tyrosine kinase inhibitors (TKIs)
             within 14 days prior to the first dose of cediranib, with cetuximab within 30 days
             prior to the first dose of cediranib, or with bevacizumab within 60 days prior to the
             first dose of cediranib

          -  Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count ≤1.5 x
             109/L or platelet count ≤100 x 109/L

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2,5 x ULN

          -  Serum creatinine > 1.5 x ULRR or a creatinine clearance of ≤ 50mL/min calculated by
             Cockcroft-Gault

          -  Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week
             apart unless urinary protein < 1.5g in a 24 hr period

          -  Prothrombin time (PT) and activated partial thromboplastin time (APTT) > 2 x ULN
             History of significant gastrointestinal impairment, as judged by the Investigator,
             that would significantly affect the absorption of cediranib, including the ability to
             swallow the tablet whole. Patients with an ileostoma.

          -  Patients with a history of poorly controlled hypertension with resting blood pressure
             >150/100 in the presence or absence of a stable regimen of anti-hypertensive therapy.
             Patients who are currently receiving maximal doses of calcium channel blockers or more
             than 1 antihypertensive for the treatment of hypertension are also ineligible.

          -  Any evidence of severe or uncontrolled diseases e.g., unstable or uncompensated
             respiratory, cardiac, hepatic or renal disease.

          -  Unresolved toxicity > CTC grade 1 from previous anti-cancer therapy (including
             radiotherapy) except alopecia (if applicable) or polyneuropathy.

          -  Mean QTc with Bazetts correction >470msec in screening ECG or history of familial long
             QT syndrome

          -  Significant haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis
             (>5mL fresh blood in previous 4 weeks)

          -  Recent (<14 days) major surgery prior to entry into the study, or a surgical incision
             that is not fully healed

          -  Pregnant or breast-feeding women or women of childbearing potential with a positive
             pregnancy test prior to receiving study medication

          -  Known risk of the patient transmitting HIV, hepatitis B or C via infected blood

          -  Treatment with an investigational (non-registered) drug within 30 days prior to the
             first dose of cediranib

          -  Other concomitant anti-cancer therapy (including LHRH agonists) except steroids

          -  Concomitant use of any medication that may significantly affect hepatic cytochrome
             P450 drug metabolising activity by way of enzyme induction (e.g., phenytoin) or
             inhibition (e.g., ketoconazole, ritonavir, erythromycin) within 2 weeks if the first
             dose of cediranib and throughout the study period

          -  Patients being treated with anticoagulants (with the exception of low molecular weight
             heparin).

          -  Patients previously treated with anthracyclines (total of > 550 mg/m2 doxorubicine)
             and an ejection fraction on the MUGA scan below 40%
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 61-year-old man comes to the clinic due to nonproductive cough and progressive dyspnea.  The patient's medical conditions include hypertension, hypercholesteremia and peptic ulcer disease.  He smokes 2 packs of cigarettes daily for the past 30 years.  On examination, there are decreased breath sounds and percussive dullness at the base of the left lung.  Other vital signs are normal. Abdomen is soft without tenderness. CT scan shows a left-sided pleural effusion and nodular thickening of the pleura. The plural fluid was bloody on thoracentesis. Biopsy shows proliferation of epithelioid-type cells with very long microvilli.

Patient description (patient's own words): I am 61 and I had to go to the clinic because I couldn't stop coughing and I experienced some breath shortness. I suffer from hypertension and cholesterol and I also have a stomach ulcer. I should admit that I've been smoking 2 packs of cigarettes every day for the past 30 years. My doctor told me that my breath in my left lung sounds bad. But he told me that my blood pressure, heart rate, breathing rate and temperature are normal. My belly is also normal. However my X-Rays show some liquid on the left side and a mass where the liquid got hard. The scary thing is that the liquid was bloody when they got it out. They did a biopsy and it showed that I have an increase of epithelioid-type cells with very long microvilli.

Does the patient match the trial criteria? 1