ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01260688
Recruitment Status : Completed
First Posted : December 15, 2010
Results First Posted : December 5, 2013
Last Update Posted : May 16, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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
Hormone Refractory Prostate Cancer Recurrent Prostate Cancer Drug: cediranib maleate Drug: dasatinib Phase 2

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.


Study Type : Interventional  (Clinical Trial)
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 : October 2010
Actual Primary Completion Date : January 2013
Actual Study Completion Date : February 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Dasatinib

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 Name: Recentin

Drug: dasatinib
Given orally
Other Name: 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 Name: Recentin




Primary Outcome Measures :
  1. 12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Cycle 1 (average of 28 days) ]
    Discontinuation of treatment in cycle 1 (average of 28 days)

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

  6. Non-AE Related Treatment Discontinuation [ Time Frame: Through study completion (median duration on study = 4 cycles) ]
    Non-Adverse Event related Treatment Discontinuation

  7. Overall Response Rate [ Time Frame: Duration of Study (median duration on study = 4 cycles) ]
    Best overall response rate of each evaluable patient

  8. Treatment Related Deaths [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Through study completion (median duration on study = 4 cycles) ]
    Number of participants with increased alkaline phosphatase BAP

  11. Dose Interruption Due to AEs [ Time Frame: 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 [ Time Frame: Duration of Study (median duration on study = 4 cycles) ]
    The number of participants with dose reductions in each arm

  13. Overall Response Rate [ Time Frame: 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 [ Time Frame: Up to 16 weeks ]
    Scale is measured on a range from 0 (worst quality of life) to 156 (best quality of life).



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
National Cancer Institute (NCI)
Investigators
Principal Investigator: Sebastien Hotte University Health Network-Princess Margaret Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01260688     History of Changes
Other Study ID Numbers: NCI-2011-02544
PMH-PJC-002 ( Other Identifier: University Health Network )
PJC-002 ( Other Identifier: Local protocol number )
8476 ( Other Identifier: NIH protocol number )
U01CA070095 ( U.S. NIH Grant/Contract )
U01CA132123 ( U.S. NIH Grant/Contract )
N01CM00071 ( U.S. NIH Grant/Contract )
First Posted: December 15, 2010    Key Record Dates
Results First Posted: December 5, 2013
Last Update Posted: May 16, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Cediranib
Dasatinib
Maleic acid
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors