None listed
Conditions
Interventions
Treatment group 1:
Type of group
Treatment group 1:
Romiplostim is supplied in a 5 mL single-use vial as a sterile, white, preservative-free, lyophilized powder containing histidine, mannitol, sucrose, and polysorbate 20, and has a pH 5.0 when reconstituted with sterile water for injection.
Subjects will receive weekly subcutaneous injections of investigational product throughout the treatment period, starting at 2 μ
g/kg and increasing by increments of 1 μ
g/kg to a maximum dose of 10 μ
g/kg to reach a target platelet count of ≥
100 x 109/L. increasing by increments of 1 μ
Treatment group 2: Type of group
Placebo will be provided in identical 5 mL single-use vials as a sterile, white, preservative-free, lyophilized powder containing histidine, mannitol, sucrose, and polysorbate 20 and has a pH 5.0 when reconstituted with sterile water for injection.
Subjects will receive weekly subcutaneous injections of investigational product throughout the treatment period, starting at 2 μ
100 x 109/L.
Sponsors
AMGEN INC.,
Eligibility
Inclusion criteria
Inclusion criteria: - Subject has provided informed consent prior to initiation of any study specific activities/procedures or subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent. - Males or females ≥ 18 years of age at signing of the informed consent. - Histologically or cytologically confirmed diagnosis of gastrointestinal or colorectal adenocarcinoma, defined as cancers of the esophagus, stomach, colon, or rectum. Tumor stage will not affect eligibility. - Subjects must be receiving a FOLFOX-based chemotherapy regimen, containing 5-FU and oxaliplatin, on a 14-day schedule. Note: Use of a FOLFOX-based combination regimen is permitted with (1) anti-angiogenic agents (such as bevacizumab) or (2) targeted therapy (such as anti-epidermal growth factor receptor agents). FOLFOXIRI-based regimens will not be allowed. - Subjects must have a platelet count < 75 x 109/L on study day 1. - Subjects must be at least 14 days removed from the start of the chemotherapy cycle immediately prior to study day 1. - Subjects must have at least 3 remaining planned cycles of chemotherapy at study enrollment. - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Exclusion criteria
Exclusion criteria: Previous or Current Medical Conditions - Acute lymphoblastic leukemia. - Acute myeloid leukemia. - Any myeloid malignancy. - Myelodysplastic syndrome. Baseline bone marrow biopsy is not required to rule out MDS. However, if a bone marrow biopsy and cytogenetics were performed as part of diagnostic or staging work-up, these results will be collected to confirm. - Myeloproliferative disease. - Multiple myeloma. - Within 4 months prior to enrollment, any history of active congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT interval of > 470 msec, pericardial disease, or myocardial infarction. - Major surgery ≤ 28 days or minor surgery ≤ 3 days prior to enrollment. - New or uncontrolled venous thromboembolism or thrombotic events within 3 months prior to screening. To be eligible, subjects must have received at least 14 days of anticoagulation for a new thrombotic event and considered to be both stable and suitable for continued therapeutic anticoagulation during trial participation. - History of arterial thrombosis (eg, stroke or transient ischemic attack) within 6 months of screening. - Evidence of active infection within 2 weeks prior to first dose of study treatment. - Known human immunodeficiency virus infection. Subjects without a documented diagnosis in their medical history will require a central laboratory assessment at screening. - Known active chronic hepatitis B or C infection. Subjects without a documented diagnosis in their medical history will require a central laboratory assessment at screening. Hepatitis B and C infection is based on the following results: • Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B). • Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by PCR is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B. • Positive Hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C. - In addition to Acute lymphoblastic leukemia and Multiple myeloma, secondary malignancy within the past 5 years except: • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. • Adequately treated cervical carcinoma in situ without evidence of disease. • Adequately treated breast ductal carcinoma in situ without evidence of disease. • Prostatic intraepithelial neoplasia without evidence of prostate cancer. • Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ. • Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician (excluding Acute lymphoblastic leukemia and Multiple myeloma). - Thrombocytopenia due to another etiology other than CIT (eg, chronic liver disease, prior history of immune thrombocytopenia purpura). Prior/Concomitant Therapy - Previous use of romiplostim, pegylated recombinant human megakaryocyte growth and development factor, eltrombopag, recombinant human TPO, any other TPO receptor agonist, or any investigationa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:A 2-sided CMH test will be used to compare groups controlling for the stratification factors of tumor type and baseline platelet count. The Mantel-Haenszel estimate of common odds ratio for romiplostim vs placebo will be estimated along with a 95% CI for each treatment group and the difference in proportions between treatment groups will be provided with a 95% CI. Measure:Primary endpoint, which is no thrombocytopenia-induced modification of any myelosuppressive treatment agent. Chemotherapy dose modification includes dose reduction, delay, omission, and discontinuation. Timepoints:second and third cycles of the planned on-study chemotherapy regimen. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Linear regression models will be used to compare the mean nadir between the romiplostim and placebo groups. The normality assumption for linear regression models will be checked using a normal probability plot of the residuals and the Shapiro-Wilk test. Measure:Depth of Platelet Nadir Timepoints:from the start of the first on-study chemotherapy cycle through the EOTP. ; Outcome name:A 2-sided log-rank test stratified by tumor type and baseline platelet count will be performed to determine whether time to first platelet response is significantly different between treatment groups. The hazard ratio of achieving platelet response for romiplostim vs placebo and its corresponding 2-sided 95% CI will be provided using a stratified Cox regression model. Kaplan-Meier curves for the time to achieving first platelet response will be presented along with Kaplan-Meier rates and 2-sided 95% CIs at specified time points (week 3, week 4, etc) for each treatment group. In addition, Kaplan-Meier quartiles (median, 25th, and 75th percentiles) will be estimated with 2-sided 95% CI, if estimable. Measure:Time to Platelet Response. Timepoints:from the study day 1 to the date of achieving first platelet count ≥ 100 x 109/L ; Outcome name:An Andersen-Gill model with a robust variance estimator, stratified by tumor type and baseline platelet count, will be used to analyze recurrent bleeding events and will provide hazard ratio with 95% CI and p-value comparing treatment groups. Measure:Duration-adjusted Event Rate of ≥ Grade 2 Bleeding Events Timepoints:from study day 1 until the date of last dose of investigational product plus 30 days ; Outcome name:A 2-sided stratified log rank will test differences of survival rates between the two treatment groups. A hazard ratio with 95% CI from a stratified Cox regression model will describe the treatment effect. Measure:Overall Survival Tim | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Chile, Colombia, France, Greece, Hungary, Italy, Mexico, Poland, Portugal, Romania, Russian Federation, Spain, Turkey, Ukraine, United States
Contacts
Public ContactClaudia Zamata
IQVIA RDS Peru S.R.L
Outcome results
None listed