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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
123
15 milligrams per kilogram (mg/kg) intravenous (IV) Days 1 and 8
Mitoxantrone 12 milligrams per square meter (mg/m²) IV Day 1 Mitoxantrone is to be administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²)
5 mg orally (PO) twice daily (BID) on each day
Progression-Free Survival (PFS)
PFS is measured from randomization to the earliest date of the following events: PD according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version (v) 1.1, is a ≥20% increase in the sum of diameter of the target lesions taking as reference the smallest sum on study and an absolute increase in the sum diameter of ≥5 millimeter (mm), the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions, unequivocal evidence of progression by bone scan, clinical progression or death from any cause. For participants who had no documented PD or death or had started new anti-cancer therapy or were lost to follow-up, PFS was censored at their last tumor assessment.
Time frame: Randomization to Measured PD or Death Due to Any Cause Up to 23 Months
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death from any cause. If the participants were alive at the end of the follow-up period or were lost to follow-up, OS time was censored on the last date the participant was known to be alive.
Time frame: Randomization to Death Due to Any Cause Up to 36 Months
Percentage of Participants Who Achieved a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Best response is categorized using the RECIST v1.1 guidelines. CR is the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 mm. PR is a ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the pretreatment sum diameter. Percentage of participants = (number of participants who had CR or PR) / (number of participants treated) \* 100.
Time frame: Randomization to Objective PD or Death Up to 23 Months
Percentage of Participants With a ≥50% Decrease in Prostate Specific Androgen (PSA) From Pretreatment to Any Time
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ImClone Investigational Site
Charleroi, Belgium
ImClone Investigational Site
Edegem, Belgium
ImClone Investigational Site
Liège, Belgium
ImClone Investigational Site
Olomouc, Czechia
ImClone Investigational Site
Prague, Czechia
ImClone Investigational Site
Prague, Czechia
ImClone Investigational Site
Aachen, Germany
ImClone Investigational Site
Augsburg, Germany
ImClone Investigational Site
Bonn, Germany
ImClone Investigational Site
Dresden, Germany
...and 30 more locations
Decrease in PSA ≥50% from pretreatment required confirmation no less than 3 weeks after the initial suggestion of response and occurring prior to documentation of PD. Percentage of participants = (number of participants who had ≥50% decrease in PSA at any time) / (number of participants treated) \* 100.
Time frame: Pretreatment to PD Up to 23 Months
Percentage of Participants With a ≥30% Decrease in PSA From Pretreatment to Week 12
Percentage of participants = (number of participants who had ≥30% decrease in PSA at Week 12) / (number of participants treated) \* 100.
Time frame: Pretreatment through Week 12
Summary Listing of Participants Reporting Treatment-Emergent Adverse Events (TEAE)
Data presented are the number of participants who experienced serious adverse events (SAEs) and other nonserious adverse events (AEs). For participants in mitoxantrone group who had PD and chose optional IMC-3G3 follow-on treatment, the baseline was defined as the last assessment prior to the start of the olaratumab treatment. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Time frame: From Start of Treatment Through Study Completion Up to 36 months
PFS Based on Baseline Circulating Tumor Cells (CTC) Counts
High expression (HE) of CTC was defined as having CTC counts ≥5 cells/7.5 milliliter (mL) and low expression (LE) of CTC was defined as having CTC counts \<5 cells/7.5 mL. PFS is measured from randomization to the earliest date of the following events: PD according to RECIST criteria v. 1.1, is a ≥20% increase in the sum diameter of the target lesions taking as reference the smallest sum on study and an absolute increase in the sum diameter of ≥5 mm, the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions, unequivocal evidence of progression by bone scan, clinical progression or death from any cause.
Time frame: Randomization to Measured PD or Death Due to Any Cause Up to 23 Months
OS Based on Baseline CTC Counts
HE of CTC was defined as having CTC counts ≥5 cells/7.5 mL and LE of CTC was defined as having CTC counts \<5 cells/7.5 mL. OS was defined as the time from the date of randomization to the date of death from any cause.
Time frame: Randomization to Death Due to Any Cause Up to 36 Months
Number of Participants With Negative Platelet-Derived Growth Factor Receptor Alpha (PDGFRα) Protein Expression by Immunohistochemistry (IHC)
PDGFRα protein expression (pretreatment) by IHC was assessed in tumor cells, and was provided as a dichotomous variable with "positive" and "negative" expression. "Positive" corresponds to weak intensity membranous staining comprising greater than 30% of the tumor and/or moderate to strong intensity membranous staining comprising greater than 5% of the tumor. "Negative" corresponds to staining that does not meet these requirements.
Time frame: Baseline
Percentage of Participants With Anti-Olaratumab Antibody Assessment (Immunogenicity)
Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
Time frame: From Start of Treatment up to 9 Months
Maximum Concentration (Cmax) of Olaratumab Cycles 1, 2 and 3
Time frame: Day 1 of Cycles 1, 2 and 3, and Day 8 of Cycles 1 and 3 (21-day cycle)