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

NCT01260688 | Completed Phase 2 Results

• 7 other identifiers: NCI-2011-02544PMH-PJC-002PJC-0028476U01CA070095U01CA132123N01CM00071
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 8

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.

Conditions

Hormone Refractory Prostate Cancer; Recurrent Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Number of Participants With Toxicities

  Up to 30 days after last dose of study drugs

• Qualtiy of Life Assessment Number of Participants With a Score ≥2 on the Present Pain Intensity (PPI) Scale

  After every cycle (median duration on study = 4 cycles)

• Number Who Experienced Study Medication Dose Intensity

  Cycle 1 (an average of 28 days)

• Treatment Discontinuation

  Cycle 1 (average of 28 days)

• Treatment Discontinuation Due to Adverse Events (AEs)

  Through study completion (median duration on study = 4 cycles)

Study Arms (2)

Arm I

EXPERIMENTAL

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; Drug: dasatinib

Arm II

EXPERIMENTAL

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

Interventions

cediranib maleate DRUG

Given orally

Also known as: Recentin

Arm I; Arm II

dasatinib DRUG

Given orally

Also known as: BMS-354825

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• \>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
• weeks since prior anti-androgens
• weeks since prior chemotherapy following docetaxel for metastatic disease (Any number of regimens allowed)
• weeks since prior hormonal therapy or abiraterone

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Central Illinois Hematology Oncology Center

Springfield, Illinois, 60702, United States

Location

Fort Wayne Medical Oncology and Hematology Inc - State Boulevard

Fort Wayne, Indiana, 46845, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• 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.

  PMID: 24788563 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cediranib; Dasatinib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

Clinical development discontinuation of Cediranib leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Dr. Lillian Siu
• Organization: Princess Margaret Cancer Centre

lillian.siu@uhn.ca

416-946-2911

Study Officials

• Sebastien Hotte

  University Health Network-Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2010
• First Posted: December 15, 2010
• Study Start: October 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: February 1, 2014
• Last Updated: August 8, 2018
• Results First Posted: December 5, 2013

Record last verified: 2018-07

Locations

US (5); CA (3)