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A Phase II Study of Cediranib as Palliative Treatment in Patients With Symptomatic Malignant Ascites or Pleural Effusion

Phase 2
18 Years
Not Enrolling
Malignant Ascites, Malignant Pleural Effusion

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Trial Information

A Phase II Study of Cediranib as Palliative Treatment in Patients With Symptomatic Malignant Ascites or Pleural Effusion

Malignant ascites is a difficult clinical problem. Increasing intra-abdominal pressure
resulting from fluid accumulation may cause anorexia, sleep disturbance, pain, dyspnoea,
abdominal distension, fatigue, nausea vomiting and reduced mobility. The main complaints of
pleural effusion are dyspnoea and cough. Paracentesis and thoracentesis provide relief for a
very limited period.

Studies have shown high concentrations of VEGF in malignant ascites and pleural effusion.
Beneficial effects of treatment with an intravenous or intraperitoneal antibody against VEGF
on malignant ascites have been reported. In the recent past we have treated two patients
with symptomatic malignant ascites (colorectal cancer and ovarian cancer, respectively) in a
phase I study with cediranib. Shortly after start of cediranib, within a couple of days, the
ascites disappeared. However, after stopping cediranib for progressive disease on other
sites the ascites reappeared within days. Therefore, one of those patients was treated with
cediranib as palliative treatment until two days before his death, which was beneficial for
this patient.

In this phase II study we would like to investigate the effects of treatment with cediranib
as palliative treatment on malignant ascites or pleural effusion.

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

- 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%

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

puncture free survival

Outcome Description:

If the puncture free survival after start of treatment with cediranib (time to first need for paracentesis or thoracentesis or time to death, which event occurred first) is more than 44 days the treatment of ascites and/or pleural effusion with cediranib is effective.

Outcome Time Frame:

44 days

Safety Issue:


Principal Investigator

C.M.L. van Herpen, Md PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Medical Centre Nijmegen


Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study ID:




Start Date:

April 2010

Completion Date:

Related Keywords:

  • Malignant Ascites
  • Malignant Pleural Effusion
  • cediranib
  • malignant ascites
  • malignant pleural effusion
  • Ascites
  • Pleural Effusion
  • Pleural Effusion, Malignant