Cediranib Maleate With or Without Dasatinib in Patients With Hormone-Resistant Prostate Cancer Resistant to Treatment With Docetaxel

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01260688
First received: December 14, 2010
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

This randomized phase II trial is studying the side effects and how well giving cediranib maleate together with or without dasatinib works in treating patients with hormone-resistant prostate cancer resistant to treatment with docetaxel. Cediranib maleate and dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. It is not yet known whether giving cediranib maleate together with dasatinib or alone is an effective treatment for prostate cancer.


Condition Intervention Phase
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Drug: cediranib maleate
Drug: dasatinib
Procedure: assessment of therapy complications
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Compared between the two arms using Z test.


Secondary Outcome Measures:
  • Incidence of Toxicities Graded According to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 30 days after last dose of study drugs ] [ Designated as safety issue: Yes ]
  • Symptom Assessment Using FACT-P Questionnaire and PPI Scale [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: October 2010
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: cediranib maleate
Given orally
Drug: dasatinib
Given orally
Procedure: assessment of therapy complications
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II
Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: cediranib maleate
Given orally
Procedure: assessment of therapy complications
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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 Response Evaluation Criteria in Solid Tumors (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.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 following:

      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Lymphangitis cutis/pulmonis
      • Inflammatory breast disease
      • Abdominal masses not followed by computed tomography (CT) or magnetic resonance imaging (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 (luteinizing hormone-releasing hormone [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/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9 g/dL
  • International normalized ratio (INR) =< 1.3
  • Total bilirubin =< 1.25 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.0 times ULN (5 times ULN if clearly attributable to liver metastasis)
  • Creatinine normal OR creatinine clearance >= 60 mL/min
  • Left ventricular ejection fraction (LVEF) > institutional normal range by echocardiogram (ECHO)/multiple gated acquisition (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 blood pressure (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
  • Patients with QTc prolongation (defined as a QTc interval greater than or equal to 480 msec by Fridericia correction) or other significant electrocardiogram (ECG) abnormalities (i.e. clinically significant arrhythmias requiring medication, conduction delays such as 2nd or 3rd degree atrioventricular blocks, etc) are ineligible

    • Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to EKG to rule out QTc prolongation
  • 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
      • New York Heart Association (NYHA) class III or IV heart failure
      • Myocardial infarction
      • Cardiac angioplasty, stenting, or bypass
      • Ventricular tachyarrhythmia within 6 months
      • Major conduction abnormality (unless a cardiac pacemaker is present)
      • Patients with underlying cardiopulmonary dysfunction should be excluded from the study
  • 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 human immunodeficiency virus (HIV)-positive patients
  • No unresolved toxicity >= Common Toxicity Criteria (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 restarted
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01260688

Locations
United States, Illinois
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 60702
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
Fort Wayne, Indiana, United States, 46845
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Canada, British Columbia
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Investigators
Principal Investigator: Sebastien Hotte University Health Network-Princess Margaret Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01260688     History of Changes
Other Study ID Numbers: NCI-2011-02544, NCI-2011-02544, PMH-PJC-002, CDR0000687955, PJC-002, 8476, U01CA070095, U01CA132123, N01CM00071
Study First Received: December 14, 2010
Results First Received: October 7, 2013
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Cediranib
Dasatinib
Maleic acid
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014