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A Phase 2 Randomized Study of Cediranib (AZD2171) Alone Compared With the Combination of Cediranib (AZD2171) Plus BMS-354825 (Dasatinib, Sprycel) in Docetaxel Resistant, Castration Resistant Prostate Cancer

Phase 2
18 Years
Open (Enrolling)
Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer

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Trial Information

A Phase 2 Randomized Study of Cediranib (AZD2171) Alone Compared With the Combination of Cediranib (AZD2171) Plus BMS-354825 (Dasatinib, Sprycel) in Docetaxel Resistant, Castration Resistant Prostate Cancer


I. To determine the progression-free survival of patients with docetaxel-resistant and
castration-resistant prostate cancer treated with cediranib maleate with versus without


I. To confirm the safety and tolerability of cediranib maleate with versus without dasatinib
in these patients.

II. To calculate objective response rates of cediranib maleate with versus without
dasatinib, according to RECIST criteria, in patients with measurable disease at baseline.

III. To perform symptom assessment using the FACT-P questionnaire and the Present Pain
Intensity (PPI) scale from the McGill-Melzack questionnaire.

IV. To explore bone resorption markers (e.g., c-telopeptide and bone alkaline phosphatase),
and to correlate these biomarkers with clinical outcome.

OUTLINE: This is a multicenter study. Patients are stratified according to the presence of
soft tissue (visceral or nodal) vs bone-only disease. Patients are randomized to 1 of 2
treatment arms.

ARM I: Patients receive oral cediranib maleate once daily and oral dasatinib once daily on
days 1-28. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

ARM II: Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.

Patients may undergo blood sample collection for bone resorption marker studies. Patients'
archived tumor specimens are also analyzed for c-Src protein expression and activity.
Patients complete the Functional Assessment of Cancer Therapy-Prostate (FACT-P)
questionnaires and the Present Pain Intensity (PPI) scale at baseline and periodically
during study.

After completion of study therapy, patients are followed up for 4 weeks.

Inclusion Criteria:

- Histologically or cytologically confirmed prostate cancer

- Measurable or non-measurable disease

- Measurable defined as ≥ 1 lesion that can be accurately measured in ≥ 1
dimension (longest diameter to be recorded) as ≥ 20 mm by conventional
techniques or as ≥ 10 mm by spiral CT scan

- Lymph nodes considered measurable if ≥ 20 mm

- Non-measurable are all other lesions, including small lesions (longest diameter
< 20 mm by conventional techniques or < 10 mm by spiral CT scan) and the

- Bone lesions

- Leptomeningeal disease

- Ascites

- Lymphangitis cutis/pulmonis

- Inflammatory breast disease

- Abdominal masses not followed by CT or MRI

- Cystic lesions

- Patients with elevation of PSA alone without measurable or nonmeasurable disease
are not eligible

- Must have received prior hormonal therapy with medical (LHRH agonist) or surgical
(orchiectomy) castration

- Castrate level of testosterone (< 50 ng/dL) required (baseline measurement of
test not required for patients who have had surgical castration)

- Clinical and/or radiographic evidence of progression on or after docetaxel therapy

- No active pleural or pericardial effusion of any grade

- No meningeal metastases or untreated known brain metastases

- Patients with treated brain metastasis with radiologic and clinical evidence of
stability, with no evidence of cavitation or hemorrhage in the brain lesions
allowed provided that they are asymptomatic and do not require corticosteroids

- Life expectancy > 3 months

- ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- INR ≤ 1.3

- Total bilirubin ≤ 1.25 times upper limit of normal (ULN)

- AST and ALT ≤ 2.0 times ULN (5 times ULN if clearly attributable to liver metastasis)

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- LVEF > 50% by ECHO/MUGA

- Urine dipstick for protein < 1+ OR < 1 g on 24-hour urine collection

- More than 5 years since any malignancy except in situ cancer, non-metastatic basal or
squamous cell skin cancer, or other cancer for which the patient has been curatively
treated by definitive primary therapy alone and has been continuously disease-free

- Fertile patients must use effective contraception

- No condition that potentially impairs ability to swallow or absorb, including any of
the following:

- Gastrointestinal tract disease resulting in an inability to take oral medication
or a requirement for IV alimentation

- Active peptic ulcer disease

- Short gut syndrome

- Malabsorption syndrome of any type

- Total or partial bowel obstruction

- Inability to tolerate oral medications

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to cediranib or dasatinib

- No systolic BP > 150 mmHg and/or diastolic BP > 100 mmHg (with or without stable dose
anti-hypertensive medication), poorly controlled hypertension, history of labile
hypertension, or poor compliance with anti-hypertensive medication

- No QTc prolongation ≥ 450 msec, or other significant ECG abnormalities (i.e.,
clinically significant arrhythmias requiring medication, conduction delays such as
2nd or 3rd degree atrioventricular blocks, etc)

- None of the following conditions:

- Serious or non-healing wound, ulcer, or bone fracture

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within the past 28 days

- Any history of cerebrovascular accident (CVA) within the past 6 months

- History of symptomatic cardiac dysfunction within the past 12 months including,
but not limited to, any of the following:

- Unstable angina

- NYHA class III or IV heart failure

- Myocardial infarction

- Cardiac angioplasty, stenting, or bypass

- No active or uncontrolled infections, serious illness, or medical conditions that
would not permit the patient to be managed according to the protocol

- No known immunodeficiency syndrome

- No clinical or radiological evidence of severe or uncontrolled interstitial lung
disease (e.g., bilateral, diffuse, or parenchymal lung disease), or current unstable
or uncompensated respiratory conditions

- No history or concurrent idiopathic pulmonary fibrosis

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No unresolved toxicity ≥ CTC grade 2 (except alopecia) from prior anticancer therapy

- At least 4 weeks since prior anti-androgens

- At least 4 weeks since prior chemotherapy following docetaxel for metastatic disease

- Any number of regimens allowed

- At least 4 weeks since prior hormonal therapy or abiraterone

- If patient was receiving prior LHRH agonists, then therapy must be continued or

- At least 3 weeks since prior radioisotopes or radiotherapy and recovered

- Concurrent low-dose, nonmyelosuppressive radiotherapy may be allowed

- No prior therapy with angiogenesis or Src or FAK inhibitors

- Prior COX-2 inhibitor in standard dose is not considered antiangiogenic therapy

- At least 4 weeks since prior non-angiogenic therapy

- At least 3 weeks since prior major surgery and recovered

- At least 1 week since prior corticosteroids

- Concurrent low-dose corticosteroid (≤ 20 mg of prednisone daily) and appropriate
analgesics and/or narcotics allowed

- Concurrent zoledronic acid allowed provided patient has been receiving it prior to
start of study treatment

- Concurrent medications or substances known to affect or with the potential to affect
the activity or pharmacokinetics of cediranib and dasatinib will be determined
following review of their case by the principal investigator or co-investigator

- At least 14 days before and after study and no concurrent CYP3A4-active agents or
substances (including strong inhibitors or inducers)

- Concurrent prophylactic low-dose warfarin (INR must be close monitored) or
low-molecular weight heparin allowed

- No other concurrent investigational agents

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival rate as per the Prostate Cancer Clinical Trials Working Group (PCWG2)

Outcome Description:

Compared between the two arms using Z test.

Outcome Time Frame:

3 months

Safety Issue:


Principal Investigator

Sebastien Hotte

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network-Princess Margaret Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

October 2010

Completion Date:

Related Keywords:

  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Prostatic Neoplasms



Johns Hopkins University Baltimore, Maryland  21205
Central Illinois Hematology Oncology Center Springfield, Illinois  62701
Illinois CancerCare-Peoria Peoria, Illinois  61615
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard Fort Wayne, Indiana  46845