Clinical trial NCT01260688: Cediranib Maleate With or Without Dasatinib in Patients With HRPC-Resistant to Treatment With Docetaxel
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hormone Refractory Prostate Cancer
Recurrent Prostate Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-12-15
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: 12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2)
timeFrame: 3 months
Secondary outcomes:
measure: Number of Participants With Toxicities
timeFrame: Up to 30 days after last dose of study drugs
measure: Qualtiy of Life Assessment Number of Participants With a Score ≥2 on the Present Pain Intensity (PPI) Scale
timeFrame: After every cycle (median duration on study = 4 cycles)
measure: Number Who Experienced Study Medication Dose Intensity
timeFrame: Cycle 1 (an average of 28 days)
measure: Treatment Discontinuation
timeFrame: Cycle 1 (average of 28 days)
measure: Treatment Discontinuation Due to Adverse Events (AEs)
timeFrame: Through study completion (median duration on study = 4 cycles)
measure: Non-AE Related Treatment Discontinuation
timeFrame: Through study completion (median duration on study = 4 cycles)
measure: Overall Response Rate
timeFrame: Duration of Study (median duration on study = 4 cycles)
measure: Treatment Related Deaths
timeFrame: Through study completion (median duration on study = 4 cycles)
measure: Participants for Which Bone Biomarkers for Beta-C Telopeptide Was Reduced
timeFrame: Through study completion (median duration on study = 4 cycles)
measure: Number of Participants With Increased Alkaline Phosphatase BAP
timeFrame: Through study completion (median duration on study = 4 cycles)
measure: Dose Interruption Due to AEs
timeFrame: Through study completion (median duration on study = 4 cycles)
measure: Dose Reductions
timeFrame: Duration of Study (median duration on study = 4 cycles)
measure: Overall Response Rate
timeFrame: Duration of Study (median duration on study = 4 cycles)
measure: Quality of Life Assessment Using Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
timeFrame: Up to 16 weeks
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University Health Network-Princess Margaret Hospital
name: Sebastien Hotte
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.