Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects with Gastrointestinal, Pancreatic, or Colorectal Cancer
RECITE: A phase 3 Randomized Placebo-controlled Double-blind Study of Romiplostim for the Treatment of Chemotherapy-induced Thrombocytopenia in Patients Receiving Oxaliplatin-based Chemotherapy for Treatment of Gastrointestinal, Pancreatic, or Colorectal Cancer
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
165
This study is designed to study Romiplostim for the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients receiving chemotherapy for the treatment of gastrointestinal/colorectal/pancreatic cancer.
Placebo Comparator
Percentage of Participants Who Had Thrombocytopenia-induced Dose Modification
Participants met the criteria of the primary endpoint if there was no thrombocytopenia-induced modification of any myelosuppressive treatment agent in the second and third cycles of the planned on-trial chemotherapy regimen (cycles were up to 3 weeks). A thrombocytopenia-induced modification was defined as any dose reduction, dose delay, dose omission, and/or early chemotherapy treatment discontinuation due to low platelet counts less than 100 x 10\^9/L. The 95% confidence interval (CI) is based on the exact Clopper-Pearson method.
Time frame: Day 1 up to Week 12
Platelet Count Nadir at the End of the Treatment Period
The platelet count nadir from the first on-trial chemotherapy through the end of the treatment period is presented. The least squares (LS) mean platelet count nadirs were estimated using a general linear model which included treatment, stratification factors, and the interaction between treatment and the stratification factors (tumor type and baseline platelet count).
Time frame: Up to 21 weeks
Kaplan-Meier Estimate of Time to First Platelet Response
Platelet response was defined as achieving a platelet count of ≥ 100 x 10\^9/L in the absence of platelet transfusions during the preceding 7 days. Participants who did not achieve a response event during the treatment period were censored at their last platelet count assessment up to end of treatment period or at the randomization date if they did not have any post-baseline platelet assessments.
Time frame: Up to 21 weeks
Duration-adjusted Event Rate of Bleeding Events in the Treatment Period
The duration-adjusted adverse event (AE) incidence rate was the number of events per 100 subject-years from the trial day 1 until the date of last dose of investigational product + 30 days, or end of trial, whichever is earlier. It was calculated as: duration-adjusted event rate per 100 subject years (n/Subj-yr) x 100. The duration-adjusted event rate was assessed for Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 2 bleeding events. CTCAE grading for AEs ranges from Grade 1 (mild) to Grade 5 (death related to AE). Grade 2 AEs were moderate.
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Saint Bernards Medical Center
Jonesboro, Arkansas, United States
Pacific Cancer Medical Center Inc
Anaheim, California, United States
University of California Irvine
Orange, California, United States
Colorado West Healthcare System dba Grand Valley Oncology
Grand Junction, Colorado, United States
Mid Florida Hematology and Oncology Centers PA
Orange City, Florida, United States
Oncology and Hematology Associates of West Broward, PA
Tamarac, Florida, United States
Cleveland Clinic Florida
Weston, Florida, United States
Orchard Healthcare Research Inc
Skokie, Illinois, United States
Christus Saint Frances Cabrini Hospital
Alexandria, Louisiana, United States
University Medical Center New Orleans
New Orleans, Louisiana, United States
...and 107 more locations
Time frame: Up to 21 weeks
Overall Survival
Overall survival was defined as the time calculated from trial Day 1 to death. Participants who did not died were censored.
Time frame: From Day 1 up to 1 year after last dose of investigational product (IP) (max 1869 days)
Percentage of Participants Who Had Platelet Transfusions During the Treatment Period
Participants who had at least 1 platelet transfusion during the treatment period.
Time frame: Up to 21 weeks
Percentage of Participants Who Achieved a Platelet Count ≥ 100 x 10^9/L
The number of participants who achieved a platelet count ≥ 100 x 10\^9/L at any time after trial Day 1 to Week 4 (7 days after the planned third dose of IP). If a platelet transfusion occurred during the 7 days preceding a platelet count, then that platelet count was not considered as achieving the endpoint even if it is ≥ 100 x 109/L. Participants who had no platelet counts during this period were considered as not achieving achieved a platelet count ≥ 100 x 109/L. For participants who never received IP, the participants are considered as not achieving a platelet count ≥ 100 x 109/L. Weeks with no platelet count measurements (missing data) were considered as not achieving a platelet count ≥ 100 x 109/L.
Time frame: Day 1 to Week 4
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and Fatal AEs
An AE was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was an AE that started on or after the first dose of IP up to 30 days after the end of investigational product or last dose of on-trial chemotherapy (up to 3 cycles), whichever occurs later. Clinically significant changes in laboratory values were considered AEs. A SAE was defined as any untoward medical occurrence that, met at least 1 ofthe following criteria: resulted in death (fatal), immediately life-threatening,required in-patient hospitalization or prolongation of existing hospitalization,resulted in persistent or significant disability/incapacity or was a congenitalanomaly/birth defect.
Time frame: From first dose of IP to 30 days after last dose of IP: median (min, max) duration was 86.0 (31.0, 184.0) days
Number of Participants Who Developed Anti-romiplostim Antibodies and Anti-thrombopoietin (TPO) Antibodies
Blood samples were collected from all participants for the measurement of anti-romiplostim and anti-TPO binding antibodies. Participants were tested for the presence of anti-romiplostim and anti-TPO antibodies at baseline (pre-existing antibody) and post-baseline (developed antibody). Samples testing positive for binding antibodies were also be tested for neutralizing antibodies.
Time frame: Up to 21 weeks
Number of Participants Who Reported Myelodysplastic Syndromes (MDS) and SecondaryMalignancies
Events were identified using narrow search of pre-defined list of preferred terms for myelodysplastic syndromes (SMQ). Secondary malignancies included progression from myelodysplastic syndrome to acute myeloid leukemia (AML).
Time frame: From Day 1 up to 1 year after last dose of IP (max 1869 days)