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Cediranib Maleate With or Without Dasatinib in Patients With HRPC-Resistant to Treatment With Docetaxel

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01260688
Collaborator
(none)
22
Enrollment
8
Locations
2
Arms
40
Duration (Months)
2.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. 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:

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

  2. 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.

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

  4. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
22 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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
Study Start Date :
Oct 1, 2010
Actual Primary Completion Date :
Jan 1, 2013
Actual Study Completion Date :
Feb 1, 2014

Arms and Interventions

Arm Intervention/Treatment
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
Other Names:
  • Recentin

    • Drug: dasatinib
    Given orally
    Other Names:
  • BMS-354825

    		•
    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
    Other Names:
  • Recentin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2) [3 months]

      Progression is defined using the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, which includes a compilation of prostate-specific antigen (PSA), bone scan, and CT-scan assessments (Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Secondary Outcome Measures

    1. Number of Participants With Toxicities [Up to 30 days after last dose of study drugs]

      Incidence of toxicities graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4.0

    2. Qualtiy of Life Assessment Number of Participants With a Score ≥2 on the Present Pain Intensity (PPI) Scale [After every cycle (median duration on study = 4 cycles)]

      Present Pain Intensity (PPI) scale. Scale is measured 0-5, where 0=no pain, 1=mild pain, 2=discomforting pain, 3=distressing pain, 4=horrible pain and 5=excruciating pain Participants who were up to completing the assessment (did not decline) and who reported a score >=2 at the end of any cycle are reported.

    3. Number Who Experienced Study Medication Dose Intensity [Cycle 1 (an average of 28 days)]

      Number of patients who experienced study medication dose of over 80% during Cycle 1 was assessed.

    4. Treatment Discontinuation [Cycle 1 (average of 28 days)]

      Discontinuation of treatment in cycle 1 (average of 28 days)

    5. Treatment Discontinuation Due to Adverse Events (AEs) [Through study completion (median duration on study = 4 cycles)]

      Treatment discontinuation due to Adverse Events

    6. Non-AE Related Treatment Discontinuation [Through study completion (median duration on study = 4 cycles)]

      Non-Adverse Event related Treatment Discontinuation

    7. Overall Response Rate [Duration of Study (median duration on study = 4 cycles)]

      Best overall response rate of each evaluable patient

    8. Treatment Related Deaths [Through study completion (median duration on study = 4 cycles)]

      Number of treatment related deaths

    9. Participants for Which Bone Biomarkers for Beta-C Telopeptide Was Reduced [Through study completion (median duration on study = 4 cycles)]

      Participants for which beta-C telopeptide was reduced

    10. Number of Participants With Increased Alkaline Phosphatase BAP [Through study completion (median duration on study = 4 cycles)]

      Number of participants with increased alkaline phosphatase BAP

    11. Dose Interruption Due to AEs [Through study completion (median duration on study = 4 cycles)]

      The number of participants with dose-interruptions in each arm due to adverse events

    12. Dose Reductions [Duration of Study (median duration on study = 4 cycles)]

      The number of participants with dose reductions in each arm

    13. Overall Response Rate [Duration of Study (median duration on study = 4 cycles)]

      Response Rate of Stable Disease and Progressive Disease

    14. Quality of Life Assessment Using Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire [Up to 16 weeks]

      Scale is measured on a range from 0 (worst quality of life) to 156 (best quality of life).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically/cytologically confirmed prostate cancer

    • Measurable/non-measurable disease

    • Prior hormonal therapy with medical LHRH agonist or orchiectomy castration (Castrate level of testosterone (< 50 ng/dL) required)

    • Clinical/radiographic evidence of progression on or after docetaxel therapy

    • No active pleural/pericardial effusion of any grade

    • No meningeal metastases/untreated known brain metastases

    • Patients with treated brain metastasis with radiologic, clinical evidence of stability, with no evidence of cavitation/hemorrhage in the brain lesions allowed if asymptomatic and not requiring corticosteroids

    • Life expectancy >3 months

    • ECOG PS 0-2 (Karnofsky PS 60-100%)

    • ANC >= 1,500/mm^3

    • Platelet count >= 100,000/mm^3

    • Hemoglobin >= 9 g/dL

    • INR=< 1.3

    • Total bilirubin =< 1.25 times ULN

    • AST and ALT=< 2.0 times ULN (5 x ULN if clearly attributable to liver metastasis)

    • Creatinine normal OR creatinine clearance >= 60 mL/min

    • LVEF> institutional normal range by ECHO/MUGA

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

    Exclusion Criteria:

    • 5 years since any malignancy except in situ cancer, non-metastatic basal/squamous cell skin cancer, or other cancer for which the patient has been curatively treated

    • Fertile patients must use effective contraception

    • No condition that impairs ability to swallow/absorb

    • No history of allergic reactions attributed to compounds of similar chemical/biologic composition to cediranib/dasatinib

    • No systolic BP>150 mmHg and/or diastolic BP>100 mmHg

    • QTc prolongation (>=480 msec by Fridericia correction) or other significant ECG abnormalities are ineligible

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

    • No known immunodeficiency syndrome

    • No clinical/radiological evidence of severe/uncontrolled interstitial lung disease

    • No history/concurrent idiopathic pulmonary fibrosis

    • No concurrent combination antiretroviral therapy for HIV-positive patients

    • No unresolved toxicity>=CTCAE grade 2 (except alopecia) from prior anticancer therapy

    • 4 weeks since prior anti-androgens

    • 4 weeks since prior chemotherapy following docetaxel for metastatic disease (Any number of regimens allowed)

    • 4 weeks since prior hormonal therapy or abiraterone

    • 3 weeks since prior radioisotopes or radiotherapy and recovered

    • No prior therapy with angiogenesis or Src or FAK inhibitors

    • 3 weeks since prior major surgery and recovered

    • 1 week since prior corticosteroids

    • 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

    • 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

    Locations

    Site City State Country Postal Code
    1 Illinois CancerCare-Peoria Peoria Illinois United States 61615
    2 Central Illinois Hematology Oncology Center Springfield Illinois United States 60702
    3 Fort Wayne Medical Oncology and Hematology Inc - State Boulevard Fort Wayne Indiana United States 46845
    4 Johns Hopkins University Baltimore Maryland United States 21287-8936
    5 University of Michigan Ann Arbor Michigan United States 48109
    6 BCCA-Vancouver Cancer Centre Vancouver British Columbia Canada V5Z 4E6
    7 Juravinski Cancer Centre at Hamilton Health Sciences Hamilton Ontario Canada L8V 5C2
    8 University Health Network-Princess Margaret Hospital Toronto Ontario Canada M5G 2M9

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Sebastien Hotte, University Health Network-Princess Margaret Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01260688
    Other Study ID Numbers:
    • NCI-2011-02544
    • PMH-PJC-002
    • PJC-002
    • 8476
    • U01CA070095
    • U01CA132123
    • N01CM00071
    First Posted:
    Dec 15, 2010
    Last Update Posted:
    Aug 8, 2018
    Last Verified:
    Jul 1, 2018
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Dasatinib
    Cediranib

    Study Results

    Participant Flow

    Recruitment Details Study was open to recruitment on October 25, 2010 and closed to accrual on July 31, 2012. Study participants were identified in clinic. The target enrolment was 50 study participants; however only 22 participants enrolled as the study was terminated due to discontinuation of cediranib drug supply due to clinical development discontinuation.
    Pre-assignment Detail
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Period Title: Overall Study
    STARTED 11 11
    COMPLETED 11 11
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone Total
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Total of all reporting groups
    Overall Participants 11 11 22
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    2
    18.2%
    1
    9.1%
    3
    13.6%
    >=65 years
    9
    81.8%
    10
    90.9%
    19
    86.4%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.4
    (7.1)
    72.7
    (6.5)
    69
    (7.6)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    11
    100%
    11
    100%
    22
    100%
    Region of Enrollment (participants) [Number]
    Canada
    9
    81.8%
    8
    72.7%
    17
    77.3%
    United States
    2
    18.2%
    3
    27.3%
    5
    22.7%

    Outcome Measures

    1. Primary Outcome
    Title 12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2)
    Description Progression is defined using the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, which includes a compilation of prostate-specific antigen (PSA), bone scan, and CT-scan assessments (Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
    Time Frame 3 months

    Outcome Measure Data

    Analysis Population Description
    All patients were included in the analysis for 12-week PFS.
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive oral cediranib maleate once daily for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Number [participants]
    2
    18.2%
    8
    72.7%
    2. Secondary Outcome
    Title Number of Participants With Toxicities
    Description 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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description Patients receive oral cediranib maleate (20mg) once daily and oral dasatinib (100mg) once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients receive oral cediranib maleate (20mg) once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
    Measure Participants 11 11
    Number [participants]
    11
    100%
    11
    100%
    3. Secondary Outcome
    Title Qualtiy of Life Assessment Number of Participants With a Score ≥2 on the Present Pain Intensity (PPI) Scale
    Description Present Pain Intensity (PPI) scale. Scale is measured 0-5, where 0=no pain, 1=mild pain, 2=discomforting pain, 3=distressing pain, 4=horrible pain and 5=excruciating pain Participants who were up to completing the assessment (did not decline) and who reported a score >=2 at the end of any cycle are reported.
    Time Frame After every cycle (median duration on study = 4 cycles)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed patients receiving single agent cediranib or combination of cediranib plus dasatinib.
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Count of Participants [Participants]
    4
    36.4%
    8
    72.7%
    4. Secondary Outcome
    Title Number Who Experienced Study Medication Dose Intensity
    Description Number of patients who experienced study medication dose of over 80% during Cycle 1 was assessed.
    Time Frame Cycle 1 (an average of 28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Number [participant]
    6
    9
    5. Secondary Outcome
    Title Treatment Discontinuation
    Description Discontinuation of treatment in cycle 1 (average of 28 days)
    Time Frame Cycle 1 (average of 28 days)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on study participants enrolled on the trial assessing number of patients who discontinued treatment in cycle 1.
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Count of Participants [Participants]
    7
    63.6%
    6
    54.5%
    6. Secondary Outcome
    Title Treatment Discontinuation Due to Adverse Events (AEs)
    Description Treatment discontinuation due to Adverse Events
    Time Frame Through study completion (median duration on study = 4 cycles)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Number [participants]
    2
    18.2%
    1
    9.1%
    7. Secondary Outcome
    Title Non-AE Related Treatment Discontinuation
    Description Non-Adverse Event related Treatment Discontinuation
    Time Frame Through study completion (median duration on study = 4 cycles)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Progressive Disease
    4
    36.4%
    4
    36.4%
    Death
    0
    0%
    2
    18.2%
    Other
    5
    45.5%
    4
    36.4%
    8. Secondary Outcome
    Title Overall Response Rate
    Description Best overall response rate of each evaluable patient
    Time Frame Duration of Study (median duration on study = 4 cycles)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Median (95% Confidence Interval) [months]
    2.6
    6.4
    9. Secondary Outcome
    Title Treatment Related Deaths
    Description Number of treatment related deaths
    Time Frame Through study completion (median duration on study = 4 cycles)

    Outcome Measure Data

    Analysis Population Description
    In Arm II (Cediranib alone), 1 patient presented retroperitoneal hemorrhage (Grade 5).
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Number [participants]
    0
    0%
    1
    9.1%
    10. Secondary Outcome
    Title Participants for Which Bone Biomarkers for Beta-C Telopeptide Was Reduced
    Description Participants for which beta-C telopeptide was reduced
    Time Frame Through study completion (median duration on study = 4 cycles)

    Outcome Measure Data

    Analysis Population Description
    Analysis was done on study participatns for which beta-C telopeptide was reduced.
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 9
    Count of Participants [Participants]
    7
    63.6%
    6
    54.5%
    11. Secondary Outcome
    Title Number of Participants With Increased Alkaline Phosphatase BAP
    Description Number of participants with increased alkaline phosphatase BAP
    Time Frame Through study completion (median duration on study = 4 cycles)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 9 11
    Number [participants]
    5
    45.5%
    10
    90.9%
    12. Secondary Outcome
    Title Dose Interruption Due to AEs
    Description The number of participants with dose-interruptions in each arm due to adverse events
    Time Frame Through study completion (median duration on study = 4 cycles)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on study participants assessing the number of participants with dose-interruptions due to adverse events.
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Count of Participants [Participants]
    8
    72.7%
    6
    54.5%
    13. Secondary Outcome
    Title Dose Reductions
    Description The number of participants with dose reductions in each arm
    Time Frame Duration of Study (median duration on study = 4 cycles)

    Outcome Measure Data

    Analysis Population Description
    Analysis conducted on the number of participants with dose reductions in each arm of the study.
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Count of Participants [Participants]
    5
    45.5%
    4
    36.4%
    14. Secondary Outcome
    Title Overall Response Rate
    Description Response Rate of Stable Disease and Progressive Disease
    Time Frame Duration of Study (median duration on study = 4 cycles)

    Outcome Measure Data

    Analysis Population Description
    Analysis of number of participants who experienced response rates of SD and PD.
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 11 11
    Stable Disease
    22
    200%
    77
    700%
    Progressive Disease
    45
    409.1%
    18
    163.6%
    15. Secondary Outcome
    Title Quality of Life Assessment Using Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
    Description Scale is measured on a range from 0 (worst quality of life) to 156 (best quality of life).
    Time Frame Up to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    Some participants (overall and post-baseline) did not complete the questionnaire or failed to answer more than 7 questions and could not be included in the analysis (a summary score could not be calculated).
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description 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. Patients receive oral cediranib maleate once daily for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 10 10
    Baseline
    117.5
    108.5
    Cycle 2 (8 weeks)
    120.6
    107
    Cycle 3 (12 weeks)
    109.1
    105.8
    Cycle 4 (16 weeks)
    114.5
    93.8

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Arm/Group Description Patients receive oral cediranib maleate (20mg) once daily and oral dasatinib (100mg) once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients receive oral cediranib maleate (20mg) once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
    All Cause Mortality
    Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/11 (45.5%) 7/11 (63.6%)
    Blood and lymphatic system disorders
    Anemia 1/11 (9.1%) 1 2/11 (18.2%) 2
    Cardiac disorders
    Sinus tachycardia 0/11 (0%) 0 1/11 (9.1%) 1
    Gastrointestinal disorders
    Abdominal pain 1/11 (9.1%) 1 0/11 (0%) 0
    Upper Gastrointestinal hemorrhage 1/11 (9.1%) 1 0/11 (0%) 0
    Lower Gastrointestinal hemorrhage 1/11 (9.1%) 1 0/11 (0%) 0
    Retroperitoneal hemorrhage 0/11 (0%) 0 1/11 (9.1%) 1
    General disorders
    Fatigue 0/11 (0%) 0 2/11 (18.2%) 2
    Hepatobiliary disorders
    Bile obstruction 0/11 (0%) 0 1/11 (9.1%) 1
    Infections and infestations
    Lung infection 0/11 (0%) 0 1/11 (9.1%) 1
    Metabolism and nutrition disorders
    Dehydration 0/11 (0%) 0 1/11 (9.1%) 1
    Musculoskeletal and connective tissue disorders
    Bone Pain 0/11 (0%) 0 1/11 (9.1%) 1
    Back pain 0/11 (0%) 0 1/11 (9.1%) 1
    Chest wall pain 1/11 (9.1%) 1 0/11 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Disease progression 0/11 (0%) 0 2/11 (18.2%) 2
    Nervous system disorders
    Pending Spinal Cord compression 1/11 (9.1%) 1 0/11 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 1/11 (9.1%) 1 0/11 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm I - Cediranib Plus Dasatinib Arm II - Cediranib Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/11 (100%) 11/11 (100%)
    Blood and lymphatic system disorders
    Anemia 11/11 (100%) 11/11 (100%)
    Cardiac disorders
    Sinus tachycardia 1/11 (9.1%) 3/11 (27.3%)
    Sinus bradycardia 0/11 (0%) 2/11 (18.2%)
    Irregular heart rate and rhythm 0/11 (0%) 1/11 (9.1%)
    Ventricular Diastolic disorder 1/11 (9.1%) 0/11 (0%)
    Ventricular arrhythmia 1/11 (9.1%) 0/11 (0%)
    Ear and labyrinth disorders
    Hearing impaired 2/11 (18.2%) 0/11 (0%)
    Tinnitus 1/11 (9.1%) 0/11 (0%)
    Ear pain 1/11 (9.1%) 0/11 (0%)
    Endocrine disorders
    Hypothyroidism 3/11 (27.3%) 2/11 (18.2%)
    Gastrointestinal disorders
    Diarrhea 8/11 (72.7%) 7/11 (63.6%)
    Nausea 6/11 (54.5%) 4/11 (36.4%)
    Constipation 5/11 (45.5%) 7/11 (63.6%)
    Gastroesophageal Reflux Disease 0/11 (0%) 3/11 (27.3%)
    Stomach pain 1/11 (9.1%) 1/11 (9.1%)
    Dyspepsia 1/11 (9.1%) 3/11 (27.3%)
    Oral dysesthesia 0/11 (0%) 1/11 (9.1%)
    Abdominal pain 3/11 (27.3%) 3/11 (27.3%)
    Flatulence 1/11 (9.1%) 1/11 (9.1%)
    Bloating 0/11 (0%) 1/11 (9.1%)
    Fecal incontinence 0/11 (0%) 1/11 (9.1%)
    rectal hemorrhage 1/11 (9.1%) 1/11 (9.1%)
    hemorrhoidal hemorhage 0/11 (0%) 1/11 (9.1%)
    Hemorrhoids 0/11 (0%) 1/11 (9.1%)
    Mucositis oral 4/11 (36.4%) 1/11 (9.1%)
    Vomiting 6/11 (54.5%) 1/11 (9.1%)
    Dry mouth 2/11 (18.2%) 0/11 (0%)
    Dry throat 1/11 (9.1%) 0/11 (0%)
    Anal fissure 1/11 (9.1%) 0/11 (0%)
    Blood in stool 1/11 (9.1%) 0/11 (0%)
    Lip sore 1/11 (9.1%) 0/11 (0%)
    Sore throat 1/11 (9.1%) 0/11 (0%)
    Abdominal distension 1/11 (9.1%) 0/11 (0%)
    Gastroparesis 1/11 (9.1%) 0/11 (0%)
    Lower Gastrointestinal hemorrhage 1/11 (9.1%) 0/11 (0%)
    Upper Gastrointestinal hemorrhage 1/11 (9.1%) 0/11 (0%)
    General disorders
    Fatigue 11/11 (100%) 9/11 (81.8%)
    Edema limbs 2/11 (18.2%) 5/11 (45.5%)
    Chills 2/11 (18.2%) 1/11 (9.1%)
    Fever 2/11 (18.2%) 2/11 (18.2%)
    Malaise 1/11 (9.1%) 0/11 (0%)
    Hepatobiliary disorders
    Bile duct obstruction 0/11 (0%) 1/11 (9.1%)
    Infections and infestations
    Lung infection 1/11 (9.1%) 1/11 (9.1%)
    Mucosal infection 1/11 (9.1%) 0/11 (0%)
    Injury, poisoning and procedural complications
    Bruising 1/11 (9.1%) 2/11 (18.2%)
    Investigations
    Alkaline Phosphatase Increased 8/11 (72.7%) 10/11 (90.9%)
    Lymphocyte Count decreased 8/11 (72.7%) 9/11 (81.8%)
    Weight loss 9/11 (81.8%) 4/11 (36.4%)
    Platelet Count Decreased 5/11 (45.5%) 5/11 (45.5%)
    Electrocardiogram QT Corrected Interval Prolonged 2/11 (18.2%) 4/11 (36.4%)
    Aspartate aminotransferase Increase 8/11 (72.7%) 4/11 (36.4%)
    Creatinine increased 1/11 (9.1%) 3/11 (27.3%)
    Alanine Aminotransferase Increased 2/11 (18.2%) 2/11 (18.2%)
    Erythrocytes decreased 0/11 (0%) 1/11 (9.1%)
    White blood cell decreased 1/11 (9.1%) 2/11 (18.2%)
    Cholesterol high 0/11 (0%) 1/11 (9.1%)
    Lymphocyte count increased 0/11 (0%) 1/11 (9.1%)
    Activated partial thromboplastin time prolonged 0/11 (0%) 1/11 (9.1%)
    Neutrophil Count decreased 1/11 (9.1%) 1/11 (9.1%)
    Serum amylase increased 0/11 (0%) 1/11 (9.1%)
    Low T3 1/11 (9.1%) 0/11 (0%)
    Low T4 1/11 (9.1%) 0/11 (0%)
    Metabolism and nutrition disorders
    Obesity 1/11 (9.1%) 2/11 (18.2%)
    Anorexia 5/11 (45.5%) 6/11 (54.5%)
    Hypoalbuminemia 5/11 (45.5%) 8/11 (72.7%)
    Hyponatremia 5/11 (45.5%) 6/11 (54.5%)
    Hypocalcemia 3/11 (27.3%) 7/11 (63.6%)
    Hypophosphatemia 5/11 (45.5%) 3/11 (27.3%)
    Hypokalemia 4/11 (36.4%) 2/11 (18.2%)
    Hypomagnesemia 1/11 (9.1%) 1/11 (9.1%)
    Hyperkalemia 1/11 (9.1%) 2/11 (18.2%)
    Dehydration 0/11 (0%) 1/11 (9.1%)
    Glucose Intolerance 2/11 (18.2%) 1/11 (9.1%)
    Hypermagnesemia 0/11 (0%) 1/11 (9.1%)
    Hypernatremia 0/11 (0%) 1/11 (9.1%)
    Hyperglycemia 1/11 (9.1%) 0/11 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 3/11 (27.3%) 5/11 (45.5%)
    Arthritis 2/11 (18.2%) 3/11 (27.3%)
    Bone pain 6/11 (54.5%) 5/11 (45.5%)
    Pain in extremity 3/11 (27.3%) 1/11 (9.1%)
    Osteoporosis 0/11 (0%) 1/11 (9.1%)
    Myalgia 2/11 (18.2%) 1/11 (9.1%)
    Muscle weakness lower limb 0/11 (0%) 2/11 (18.2%)
    Restless legs 0/11 (0%) 1/11 (9.1%)
    Flank pain 0/11 (0%) 1/11 (9.1%)
    Arthralgia 1/11 (9.1%) 1/11 (9.1%)
    Blood bilirubin increased 0/11 (0%) 1/11 (9.1%)
    Muscle spasms 0/11 (0%) 1/11 (9.1%)
    Neck pain 1/11 (9.1%) 1/11 (9.1%)
    Chest wall pain 2/11 (18.2%) 0/11 (0%)
    Generalized muscle weakness 1/11 (9.1%) 0/11 (0%)
    Osteonecrosis of Jaw 1/11 (9.1%) 0/11 (0%)
    Movements involuntary 1/11 (9.1%) 0/11 (0%)
    Rib pain 1/11 (9.1%) 0/11 (0%)
    Shoulder pain 1/11 (9.1%) 0/11 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Disease Progression 0/11 (0%) 1/11 (9.1%)
    Nervous system disorders
    Peripheral Sensory Neuropathy 6/11 (54.5%) 4/11 (36.4%)
    Dysgeusia 2/11 (18.2%) 2/11 (18.2%)
    Paresthesia 0/11 (0%) 2/11 (18.2%)
    Seizure 0/11 (0%) 1/11 (9.1%)
    Headache 4/11 (36.4%) 2/11 (18.2%)
    Dizziness 3/11 (27.3%) 2/11 (18.2%)
    Spasticity 0/11 (0%) 1/11 (9.1%)
    Psychiatric disorders
    Anxiety 0/11 (0%) 3/11 (27.3%)
    Depression 3/11 (27.3%) 2/11 (18.2%)
    Insomnia 1/11 (9.1%) 4/11 (36.4%)
    Confusion 0/11 (0%) 1/11 (9.1%)
    Renal and urinary disorders
    Hematuria 2/11 (18.2%) 5/11 (45.5%)
    Urinary incontinence 1/11 (9.1%) 4/11 (36.4%)
    Proteinuria 4/11 (36.4%) 6/11 (54.5%)
    Urinary frequency 4/11 (36.4%) 2/11 (18.2%)
    Nocturia 1/11 (9.1%) 1/11 (9.1%)
    Urinary tract obstruction 0/11 (0%) 1/11 (9.1%)
    Reproductive system and breast disorders
    Erectile dysfunction 0/11 (0%) 1/11 (9.1%)
    Genital edema 0/11 (0%) 1/11 (9.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 3/11 (27.3%) 3/11 (27.3%)
    Hoarseness 0/11 (0%) 2/11 (18.2%)
    Dyspnea 4/11 (36.4%) 4/11 (36.4%)
    Voice alteration 1/11 (9.1%) 1/11 (9.1%)
    Diminished breath sounds 0/11 (0%) 1/11 (9.1%)
    Bilateral rales 0/11 (0%) 1/11 (9.1%)
    Postnasal drip 0/11 (0%) 2/11 (18.2%)
    Nasal congestion 0/11 (0%) 1/11 (9.1%)
    Epistaxis 1/11 (9.1%) 0/11 (0%)
    Runny nose 1/11 (9.1%) 0/11 (0%)
    Skin and subcutaneous tissue disorders
    Scalp dermatitis 0/11 (0%) 1/11 (9.1%)
    Skin ulceration 0/11 (0%) 1/11 (9.1%)
    Pruritus 0/11 (0%) 1/11 (9.1%)
    Rash maculo-papular 0/11 (0%) 1/11 (9.1%)
    Retroperitoneal hemorrhage 0/11 (0%) 1/11 (9.1%)
    Alopecia 2/11 (18.2%) 0/11 (0%)
    Dry skin 2/11 (18.2%) 0/11 (0%)
    Hyperhidrosis 2/11 (18.2%) 0/11 (0%)
    Palmar-Plantar Erythrodysesthesia 1/11 (9.1%) 0/11 (0%)
    Vascular disorders
    Hypertension 9/11 (81.8%) 11/11 (100%)
    Hot Flashes 4/11 (36.4%) 2/11 (18.2%)
    Thromboembolic event 0/11 (0%) 1/11 (9.1%)
    Flushing 0/11 (0%) 1/11 (9.1%)

    Limitations/Caveats

    Clinical development discontinuation of Cediranib leading to small numbers of subjects analyzed.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Dr. Lillian Siu
    Organization Princess Margaret Cancer Centre
    Phone 416-946-2911
    Email lillian.siu@uhn.ca
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01260688
    Other Study ID Numbers:
    • NCI-2011-02544
    • PMH-PJC-002
    • PJC-002
    • 8476
    • U01CA070095
    • U01CA132123
    • N01CM00071
    First Posted:
    Dec 15, 2010
    Last Update Posted:
    Aug 8, 2018
    Last Verified:
    Jul 1, 2018