Clinical trial NCT01204710: A Study of Olaratumab (IMC-3G3) in Prostate Cancer
Official title: A Randomized Phase 2 Study of Human Anti-PDGFRα Monoclonal Antibody IMC-3G3 Plus Mitoxantrone Plus Prednisone or Mitoxantrone Plus Prednisone in Metastatic Castration-Refractory Prostate Cancer Following Disease Progression or Intolerance on Docetaxel-based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-09-17
Enrollment: 123
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 is a study evaluating the safety and efficacy of the monoclonal antibody olaratumab plus mitoxantrone plus prednisone compared to mitoxantrone plus prednisone in metastatic castration-refractory prostate cancer following disease progression or intolerance on docetaxel-based chemotherapy.


Eligibility criteria: Inclusion Criteria:

* histologically-confirmed adenocarcinoma of the prostate
* radiographic evidence of metastatic prostate cancer (Stage M1 or D2)
* has prostate cancer unresponsive or refractory to medical or surgical castration with a serum testosterone level of \<50 nanograms per milliliter (ng/mL)
* has had disease progression or intolerance on docetaxel-based therapy
* prostate-specific antigen (PSA) ≥10 ng/mL
* all clinically significant toxic effects of prior surgery, radiotherapy, chemotherapy or hormonal therapy have resolved to ≤Grade 1, based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.02
* participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
* adequate hematologic function
* adequate hepatic function
* adequate renal function
* urinary protein is ≤1 on dipstick or routine analysis
* life expectancy of more than 3 months
* fertile man with partners that are women of childbearing potential must use an adequate method of contraception during the study
* signed Informed Consent Document

Exclusion Criteria:

* concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or other noninvasive or in situ neoplasms
* The participant has received more than 1 prior cytotoxic chemotherapy regimen for metastatic disease
* prior therapy with mitoxantrone for advanced prostate cancer
* The participant has a history of symptomatic congestive heart failure or has a pre study echocardiogram or multigated acquisition scan with left ventricular ejection fraction that is ≥10% below the lower limit of normal institutional range
* history of prior treatment with other agents that directly inhibit platelet-derived growth factor (PDGF) or platelet-derived growth factor receptors (PDGFR)
* known allergy to any of the treatment components: olaratumab, mitoxantrone, and/or prednisone
* radiotherapy within 21 days prior to first dose of olaratumab
* any investigational therapy within 30 days of randomization
* is receiving corticosteroids at a dose \>5 mg prednisone PO BID or equivalent
* received prior strontium-89, rhenium-186, rhenium-188, or samarium-153 radionucleotide therapy and has either ongoing evidence of bone marrow dysfunction or poorly controlled bone pain
* has any ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, psychiatric illness, active bleeding or pathological condition that carries a high risk of bleeding, or any other serious uncontrolled medical disorders
* known or suspected brain or leptomeningeal metastases
* known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Randomization to Measured PD or Death Due to Any Cause Up to 23 Months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization to Death Due to Any Cause Up to 36 Months
measure: Percentage of Participants Who Achieved a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
timeFrame: Randomization to Objective PD or Death Up to 23 Months
measure: Percentage of Participants With a ≥50% Decrease in Prostate Specific Androgen (PSA) From Pretreatment to Any Time
timeFrame: Pretreatment to PD Up to 23 Months
measure: Percentage of Participants With a ≥30% Decrease in PSA From Pretreatment to Week 12
timeFrame: Pretreatment through Week 12
measure: Summary Listing of Participants Reporting Treatment-Emergent Adverse Events (TEAE)
timeFrame: From Start of Treatment Through Study Completion Up to 36 months
measure: PFS Based on Baseline Circulating Tumor Cells (CTC) Counts
timeFrame: Randomization to Measured PD or Death Due to Any Cause Up to 23 Months
measure: OS Based on Baseline CTC Counts
timeFrame: Randomization to Death Due to Any Cause Up to 36 Months
measure: Number of Participants With Negative Platelet-Derived Growth Factor Receptor Alpha (PDGFRα) Protein Expression by Immunohistochemistry (IHC)
timeFrame: Baseline
measure: Percentage of Participants With Anti-Olaratumab Antibody Assessment (Immunogenicity)
timeFrame: From Start of Treatment up to 9 Months
measure: Maximum Concentration (Cmax) of Olaratumab Cycles 1, 2 and 3
timeFrame: Day 1 of Cycles 1, 2 and 3, and Day 8 of Cycles 1 and 3 (21-day cycle)
Other outcomes:
measure: Number of Participants Who Died During Study
timeFrame: From Start of Treatment through Study Completion up to 36 Months
Locations:
city: Charleroi
country: Belgium
facility: ImClone Investigational Site
city: Edegem
country: Belgium
facility: ImClone Investigational Site
city: Liège
country: Belgium
facility: ImClone Investigational Site
city: Olomouc
country: Czechia
facility: ImClone Investigational Site
city: Prague
country: Czechia
facility: ImClone Investigational Site
city: Praha 5
country: Czechia
facility: ImClone Investigational Site
city: Aachen
country: Germany
facility: ImClone Investigational Site
city: Augsburg
country: Germany
facility: ImClone Investigational Site
city: Bonn
country: Germany
facility: ImClone Investigational Site
city: Dresden
country: Germany
facility: ImClone Investigational Site
city: Essen
country: Germany
facility: ImClone Investigational Site
city: Frankfurt
country: Germany
facility: ImClone Investigational Site
city: Freiburg
country: Germany
facility: ImClone Investigational Site
city: Mainz
country: Germany
facility: ImClone Investigational Site
city: Mannheim
country: Germany
facility: ImClone Investigational Site
city: Münster
country: Germany
facility: ImClone Investigational Site
city: Rostock
country: Germany
facility: ImClone Investigational Site
city: Budapest
country: Hungary
facility: ImClone Investigational Site
city: Debrecen
country: Hungary
facility: ImClone Investigational Site
city: Kecskemét
country: Hungary
facility: ImClone Investigational Site
city: Miskolc
country: Hungary
facility: ImClone Investigational Site
city: Nyíregyháza
country: Hungary
facility: ImClone Investigational Site
city: Pécs
country: Hungary
facility: ImClone Investigational Site
city: Szeged
country: Hungary
facility: ImClone Investigational Site
city: Meldola
country: Italy
facility: ImClone Investigational Site
city: Milano
country: Italy
facility: ImClone Investigational Site
city: Roma
country: Italy
facility: ImClone Investigational Site
city: Rozzano
country: Italy
facility: ImClone Investigational Site
city: Trento
country: Italy
facility: ImClone Investigational Site
city: Kraków
country: Poland
facility: ImClone Investigational Site
city: Lublin
country: Poland
facility: ImClone Investigational Site
city: Poznań
country: Poland
facility: ImClone Investigational Site
city: Warszawa
country: Poland
facility: ImClone Investigational Site
city: Barcelona
country: Spain
facility: ImClone Investigational Site
city: Barcelona
country: Spain
facility: ImClone Investigational Site
city: Madrid
country: Spain
facility: ImClone Investigational Site
city: Palma de Mallorca
country: Spain
facility: ImClone Investigational Site
city: Pamplona - Navarra
country: Spain
facility: ImClone Investigational Site
city: Sabadell - Barcelona
country: Spain
facility: ImClone Investigational Site
city: Valencia
country: Spain
facility: ImClone Investigational Site
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: