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

• ClinicalTrials.gov Identifier: NCT01260688
• Recruitment Status: Completed
• First Posted: December 15, 2010
• Results First Posted: December 5, 2013
• Last Update Posted: August 8, 2018
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

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
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 Design

• 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

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 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

Outcome Measures

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).

Eligibility Criteria

• 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

Contacts and Locations

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Spreafico A, Chi KN, Sridhar SS, Smith DC, Carducci MA, Kavsak P, Wong TS, Wang L, Ivy SP, Mukherjee SD, Kollmannsberger CK, Sukhai MA, Takebe N, Kamel-Reid S, Siu LL, Hotte SJ. A randomized phase II study of cediranib alone versus cediranib in combination with dasatinib in docetaxel resistant, castration resistant prostate cancer patients. Invest New Drugs. 2014 Oct;32(5):1005-16. doi: 10.1007/s10637-014-0106-5. Epub 2014 May 3.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01260688
• 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
• Results First Posted: December 5, 2013
• Last Update Posted: August 8, 2018
• Last Verified: July 2018

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Dasatinib; Cediranib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action