Study of Romiplostim for Chemo-induced Thrombocytopenia in Adults Subjects With Gastrointestinal or Colorectal Cancer
- Inclusion: - 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. - Subjects must have a platelet count <75 x 10(9)/L on study day 1. - 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. - 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: 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 [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT (QTc) 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 polymerase chain reaction (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 the conditions listed in exclusion criteria 201 through 206, 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 malignancies listed in exclusion criteria 201 - 206). - 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 investigational platelet producing agent. Prior/Concurrent Clinical Study Experience • Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. Diagnostic Assessments - Anemia (hemoglobin 8 g/dL) on the day of initiation of investigational product as assessed by local labs. Use of red cell transfusions and erythropoietic stimulating agents is permitted throughout the study as per institutional guidelines. - Neutropenia (absolute neutrophil count 1 x 109/L) on the day of initiation of investigational product as assessed by local labs. Use of granulocyte-colony stimulating factor is permitted throughout the study as per institutional guidelines. - Abnormal renal function with creatinine clearance 30 mL/min using the Cockcroft-Gault estimated creatinine clearance as assessed by central laboratory during screening. - Abnormal liver function (total bilirubin 3X ULN; alanine aminotransferase [ALT] or aspartate aminotransferase [AST] 3X ULN for subjects without liver metastases or 5X ULN for subjects with liver metastases) as assessed by central laboratory during screening. Other Exclusions - Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after treatment (and chemotherapy) discontinuation (females of childbearing potential should only be included after a confirmed menstrual period and a negative highly sensitive urine pregnancy test.) - Females of childbearing potential unwilling to use a highly effective method of contraception during treatment and for an additional 6 months after treatment (and chemotherapy) discontinuation. Refer to Appendix 5 for additional contraceptive information. - Males unwilling to use contraception* (male condom or sexual abstinence) or their female partner(s) of childbearing potential who are unwilling to use a highly effective method of contraception during treatment (and chemotherapy) and for an additional 6 months after treatment (and chemotherapy) discontinuation. *If the male's sole partner is of non-childbearing potential, he is not required to use additional forms of contraception during the study. - Subject has known sensitivity to any of the products to be administered during dosing. - Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, COAs) to the best of the subject and investigator's knowledge. - History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. - Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment (and chemotherapy) and for an additional period of 6 months after treatment (and chemotherapy) discontinuation. - Male subjects unwilling to abstain from donating sperm during treatment (and chemotherapy) and for an additional 6 months after treatment (and chemotherapy) discontinuation.
A Phase 3 Randomized Placebo-controlled Double-blind Study of Romiplostim for the Treatment of Chemotherapy-induced Thrombocytopenia in Patients Receiving FOLFOX-based Chemotherapy for Treatment of Gastrointestinal or Colorectal Cancer
Trial Phase Phase III
Trial Type Treatment
- Primary ID 20140346
- Secondary IDs NCI-2019-04391, 2017-002992-25
- Clinicaltrials.gov ID NCT03362177