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

NCT ID: NCT01260688

Last Updated: 2018-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2014-02-28

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.

Conditions

Hormone Refractory Prostate Cancer; Recurrent Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

cediranib maleate

Intervention Type: DRUG

Given orally

dasatinib

Intervention Type: DRUG

Given orally

Arm II

Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

cediranib maleate

Intervention Type: DRUG

Given orally

Interventions

cediranib maleate

Given orally

Intervention Type: DRUG

dasatinib

Given orally

Intervention Type: DRUG

Other Intervention Names

Recentin; BMS-354825

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sebastien Hotte

Role: PRINCIPAL_INVESTIGATOR

University Health Network-Princess Margaret Hospital

Locations

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Central Illinois Hematology Oncology Center

Springfield, Illinois, United States

Fort Wayne Medical Oncology and Hematology Inc - State Boulevard

Fort Wayne, Indiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 24788563 (View on PubMed)

Other Identifiers

PMH-PJC-002

Identifier Type: OTHER

Identifier Source: secondary_id

PJC-002

Identifier Type: OTHER

Identifier Source: secondary_id

8476

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA070095

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA132123

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02544

Identifier Type: -

Identifier Source: org_study_id