MEDI-522 in the Treatment of Patients With Metastatic Androgen-Independent Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

Phase II, Randomized, Open-Label, Two-Arm, Multicenter Study of MEDI-522, a HuMA Directed Against the Human Alpha V Beta 3 Integrin, in Combination With Docetaxel, Prednisone, and Zoledronic Acid in the Treatment of Patients With Metastatic Androgen-Independent Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00072930
• Other study ID #: MI-CP098
• Status: Completed
• Phase: Phase 2
• First received: November 12, 2003
• Last updated: January 11, 2008
• Start date: December 2003
• Est. completion date: June 2007

Study information

• Verified date: January 2008
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objectives of this study are:

1. To explore the antitumor activity of MEDI-522 in combination with docetaxel, prednisone, and zoledronic acid in patients with metastatic Androgen-Independent Prostate Cancer (AIPC); and

2. To summarize the safety of MEDI-522 in combination with docetaxel, prednisone, and zoledronic acid in this patient population.

Description:

This is a Phase II, randomized, open-label, two-arm, multicenter study of MEDI-522 in combination with docetaxel, prednisone, and zoledronic acid in patients with metastatic AIPC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: June 2007
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult men at least 18 years of age at the time of randomization.

• Metastatic, histologically or cytologically confirmed adenocarcinoma of the prostate that has progressed after start of androgen deprivation therapy, which includes prior orchiectomy or medical castration using leuteinizing hormone-releasing hormone (LHRH) antagonists such as leuprolide or goserelin (patients must remain on LHRH analogue therapy for the duration of the study if not surgically castrated). Progressive disease should be documented by:

a. PSA progression (defined as two consecutive increases in PSA over a previous reference value, with the first increase in PSA occurring at a minimum of 1 week after the reference value [obtained within 2 months prior to study randomization] and confirmed by a subsequent increase in PSA whose value must be ³ 5 ng/mL prior to study randomization);41 and one of the following: i. Bone metastases (defined as ³3 foci on bone scan and confirmed radiologically within 1 month prior to study randomization); or ii. Measurable non-bony metastatic disease (documented by radiographic studies performed within 1 month prior to study randomization).

• Serum testosterone levels <50 ng/dL documented in non-surgically castrated patients within 21 days prior to randomization.

• Prior treatment with nonsteroidal antiandrogens (e.g., flutamide or bicalutamide) is allowed provided:

• There is evidence of disease progression (defined in Inclusion Criteria #2) following withdrawal of antiandrogens; and b. At least 4 weeks for flutamide or 6 weeks for bicalutamide have passed since last treatment.

• Prior treatment with ketoconazole and/or steroids is allowed provided at least 4 weeks have passed since last treatment. There are no restrictions for use of prednisone (5 mg twice daily) or another functionally equivalent oral corticosteroid for treatment of pain.

• In the rare instance a patient is potent, he must agree to practice an effective method of contraception including condom or abstinence, unless his sexual partner is sterile, from the time of first administration of MEDI-522 or docetaxel through 30 days after the last dose of either docetaxel or MEDI-522, whichever is the last drug discontinued.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 documented within 21 days prior to randomization.

• Life expectancy, in the opinion of the investigator, of at least 6 months.

• White blood cell (WBC) count = 3,000/mm3; absolute neutrophil count (ANC) = 1,500/mm3; platelet count = 100,000/mm3; and hemoglobin ³ 9 g/dL documented within 21 days prior to randomization.

• Bilirubin = ULN; aspartate transaminase (AST)/alanine transaminase (ALT) £1.5 times ULN or if AST/ALT is >1.5 times ULN, then alkaline phosphatase must be £2.5 times ULN; serum creatinine = 1.5 mg/dL; INR within normal range, unless a patient is receiving anticoagulation therapy; and corrected serum calcium between 8.0-11.5 mg/dL documented within 21 days prior to randomization.

• Patients who had prior major surgery are eligible if at least 4 weeks have passed since their surgery and all surgical wounds have healed prior to study randomization.

• Prior radiotherapy including therapeutic isotopes is allowed provided measurable or evaluable disease that is clearly progressing is present and all acute radiation-related toxicities have resolved prior to study randomization.

• Prior treatment with unconventional therapy for malignancy (e.g., vitamins, St. John's Wort, PC-SPES, saw palmetto, or other herbal remedies) is allowed provided at least 4 weeks have passed since last treatment prior to randomization.

• Written informed consent and HIPAA authorization (USA sites only) obtained from the patient prior to receipt of any study medication or beginning study procedures.

Exclusion Criteria:

• Prior chemotherapy for metastatic prostate cancer (prior adjuvant chemotherapy is allowed provided it is non-taxane based and at least 6 months have passed since last treatment).

• Prior treatment with other investigational agents within 4 weeks prior to randomization.

• Planned concurrent treatment with unconventional therapy for malignancy (e.g., vitamins, St. John's Wort, PC-SPES, saw palmetto, or other herbal other herbal remedies) based on medical history. Currently requiring anticoagulation (excluding use of heparin flush solutions for maintenance of catheter lines) for any thromboembolic disease based on medical history and physical examination.

• Current or planned participation (from the time of randomization through 30 days after the last dose of either docetaxel or MEDI-522, whichever is the last drug discontinued) in a research protocol in which an investigational agent or therapy may be administered.

• Any evidence of or history elicited by the investigator of prior treatment with MEDI-522 or MEDI-523.

• Prior treatment with calcitonin, mithramycin, or gallium nitrate within 2 weeks prior to randomization.

• Clinically evident central nervous system (CNS) metastasis.

• History of prior malignancies within the past 5 years other than adequately treated basal cell or squamous cell skin cancer or Stage I or II cancer currently in complete remission;

• Any evidence of or history elicited by the investigator of symptomatic cerebrovascular events (i.e., stroke or transient ischemic attack) within 6 months prior to randomization; or any history or evidence of pulmonary embolism or thrombophlebitis (including deep vein thrombosis) requiring anticoagulant therapy (e.g., warfarin or heparin).

• Any evidence of or history elicited by the investigator of myocardial infarction or angina within 6 months prior to randomization.

• Any evidence of or history elicited by the investigator of hematemesis, melena, hematochezia, or uncontrolled gross hematuria within 4 weeks prior to randomization.

• Any evidence of or history elicited by the investigator of bleeding diatheses.

• Major elective surgery planned from the time of randomization through 30 days after the last dose of either docetaxel or MEDI-522, whichever is the last drug discontinued.

• Any evidence of or history elicited by the investigator of hypersensitivity to a previously administered monoclonal antibody.

• Any evidence of or history elicited by the investigator of hypersensitivity to drugs formulated with polysorbate 80, prednisone (or other functionally equivalent oral corticosteroid), or zoledronic acid.

• Known human immunodeficiency virus (HIV) or known active viral hepatic infections based on medical history and physical examination.

• Any evidence of or history elicited by the investigator of uncontrolled or refractory hypertension or uncontrolled diabetes despite medication within 6 months prior to randomization.

• Any evidence of or history elicited by the investigator of an active infection requiring parenteral anti-infective therapy.

• A general medical or psychological condition or behavior, including substance dependence or abuse that, in the opinion of the investigator, might not permit the patient to complete the study or sign the informed consent.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• MEDI-522
IV at a concentration of 50 mg/mL and 10mL vials
• Docetaxel + Prednisone* + Zoledronic Acid
IV 75 mg/m2 IV 3-4 mg 5 mg

Locations

Country	Name	City	State
Belgium	A.Z. Middelheim	Antwerpen
Belgium	University Hospital Erasme	Bruxelles
Belgium	Az Groeninge	Kortrijk
Belgium	H.-Hartziekenhuis Medische Onocology-Hematologie	Roeselare
Canada	Centre Hospitalier de L'Universite de Montreal	Montreal
Hungary	Borsod County Teaching Hospital	Miskolc, H
Hungary	Szolnoki Mav Hospital	Szolnok
Israel	Sapir Medical Center - Meir Hospital	Kfar Saba
Israel	Rabin Medical Center	Petach Tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Poland	Samodzielny Publiczny Wojewodzki Szpital Zespolony	Slupsk
Russian Federation	Arkhangelsk Regional Oncology Center	Arkhangelsk
Russian Federation	Chelyabinsk Regional Oncology Center	Chelyabinsk
Russian Federation	Kazan City Oncology Center	Kazan
Russian Federation	Blokhin Cancer Research Center	Moscow
Russian Federation	Russian Research Center of Radiology	Moscow
Russian Federation	Semashko Central Clinical Hospital	Moscow
Russian Federation	Medical Rediological Research Centre of Ran	Obninsk
Russian Federation	City Clinical Oncology Dispensary	Saint Petersburg
Russian Federation	Samara Regional Oncology Center	Samara
Russian Federation	Voronezh Regional Oncology Clinical Center	Voronezh
United States	New Mexico Oncology Hematology, Consultants Ltd.	Albuquerque	New Mexico
United States	Clinical Research Services	Bismark	North Dakota
United States	SUNY Down State Medical Center	Brooklyn	New York
United States	VA Western New York Healthcare System	Buffalo	New York
United States	Associates in Oncology and Hematology	Chattanooga	Tennessee
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati, Barrett Cancer Center	Cincinnati	Ohio
United States	Danville Hematology and Oncology	Danville	Virginia
United States	North Shore Hematology Oncology Assoc., PC	East Setauket	New York
United States	Florida Cancer Specialist	Fort Myers	Florida
United States	South Valley Medical Plaza	Gilroy	California
United States	Ingalls Hospital	Harvey	Illinois
United States	Hawaii Medical Consultants	Honolulu	Hawaii
United States	Clinical Research Consultants, Inc.	Hoover	Alabama
United States	The Florida Wellcare Alliance, L.C.	Inverness	Florida
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Western Washington Oncology, Inc., P.S.	Lacey	Washington
United States	Hemotology/Oncology Associates	Lake Worth	Florida
United States	Comprehensive Cancer Center of Nevada	Las Vegas	Nevada
United States	The Community Hospital	Munster	Indiana
United States	The Sarah Cannon Cancer Center	Nashville	Tennessee
United States	Hematology Oncology Services, LLC	New Orleans	Louisiana
United States	Columbia Presbyterian Medical Center	New York	New York
United States	VA Medical Center	Northport	New York
United States	Raleigh Hematology Oncology Association	Raleigh	North Carolina
United States	VA Sierra Nevada Health Care System	Reno	Nevada
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Hubert H. Humphrey Cancer Center	Robbinsdale	Minnesota
United States	San Bernardino Urological Associates	San Bernardino	California
United States	Saint Francis Memorial Hospital	San Francisco	California
United States	Highlands Oncology Group, P.A.	Springdale	Arizona
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Stanford Advanced Medical Center	Stanford	California
United States	Santee Hematology/Oncology	Sumter	South Carolina
United States	Arizona Hematology-Oncology, P.C.	Tucson	Arizona
United States	North Mississippi Hematology & Oncology Associates, Ltd.	Tupelo	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Hungary,  Israel,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to disease progression		Baseline to disease progression	Yes
Primary	PSA Response Rate		Baseline to disease progression	Yes
Primary	Tumor Response Rate		Baseline to disease progression	Yes
Secondary	Anti-bone resorption assessed as the incidence of skeletal related events (SREs). (SREs) are defined as radiotherapy, surgery, pathologic bone fracture, spinal cord fracture. Overall survival will also be measured.		Baseline to disease progression	Yes