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

Recurrent Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01260688
• Other study ID #: NCI-2011-02544
• Secondary ID: PMH-PJC-002PJC-0
• Status: Completed
• Phase: Phase 2
• Start date: October 2010
• Est. completion date: February 2014

Study information

• Verified date: July 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: February 2014
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hormone Refractory Prostate Cancer
• Prostatic Neoplasms
• Recurrent Prostate Cancer

Intervention

Drug:
• cediranib maleate
Given orally
• dasatinib
Given orally

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
United States	University of Michigan	Ann Arbor	Michigan
United States	Johns Hopkins University	Baltimore	Maryland
United States	Fort Wayne Medical Oncology and Hematology Inc - State Boulevard	Fort Wayne	Indiana
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2)	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.	3 months
Secondary	Number of Participants With Toxicities	Incidence of toxicities graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4.0	Up to 30 days after last dose of study drugs
Secondary	Qualtiy of Life Assessment Number of Participants With a Score =2 on the Present Pain Intensity (PPI) Scale	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.	After every cycle (median duration on study = 4 cycles)
Secondary	Number Who Experienced Study Medication Dose Intensity	Number of patients who experienced study medication dose of over 80% during Cycle 1 was assessed.	Cycle 1 (an average of 28 days)
Secondary	Treatment Discontinuation	Discontinuation of treatment in cycle 1 (average of 28 days)	Cycle 1 (average of 28 days)
Secondary	Treatment Discontinuation Due to Adverse Events (AEs)	Treatment discontinuation due to Adverse Events	Through study completion (median duration on study = 4 cycles)
Secondary	Non-AE Related Treatment Discontinuation	Non-Adverse Event related Treatment Discontinuation	Through study completion (median duration on study = 4 cycles)
Secondary	Overall Response Rate	Best overall response rate of each evaluable patient	Duration of Study (median duration on study = 4 cycles)
Secondary	Treatment Related Deaths	Number of treatment related deaths	Through study completion (median duration on study = 4 cycles)
Secondary	Participants for Which Bone Biomarkers for Beta-C Telopeptide Was Reduced	Participants for which beta-C telopeptide was reduced	Through study completion (median duration on study = 4 cycles)
Secondary	Number of Participants With Increased Alkaline Phosphatase BAP	Number of participants with increased alkaline phosphatase BAP	Through study completion (median duration on study = 4 cycles)
Secondary	Dose Interruption Due to AEs	The number of participants with dose-interruptions in each arm due to adverse events	Through study completion (median duration on study = 4 cycles)
Secondary	Dose Reductions	The number of participants with dose reductions in each arm	Duration of Study (median duration on study = 4 cycles)
Secondary	Overall Response Rate	Response Rate of Stable Disease and Progressive Disease	Duration of Study (median duration on study = 4 cycles)
Secondary	Quality of Life Assessment Using Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire	Scale is measured on a range from 0 (worst quality of life) to 156 (best quality of life).	Up to 16 weeks