Chemotherapy-induced Thrombocytopenia
Conditions
Keywords
Chemotherapy-induced thrombocytopenia, Non-small Cell Lung Cancer, Ovarian Cancer, Breast Cancer
Brief summary
To evaluate the efficacy of romiplostim for the treatment of CIT in patients receiving chemotherapy for the treatment of NSCLC, ovarian cancer, or breast cancer measured by the ability to administer on-time, full-dose chemotherapy
Detailed description
This is a phase 3, randomized, placebo-controlled, multicenter, international study for the treatment of CIT in adult subjects receiving chemotherapy for the treatment of NSCLC, ovarian cancer, or breast cancer. Subjects must have a platelet count ≤ 85 x 10\^9/L on day 1 of the study. The study will consist of a screening period of up to 4 weeks, a treatment period long enough to allow for assessment of 3 planned cycles of chemotherapy, a follow-up visit, and long-term follow-up (LTFU). Given that subjects are required to have 3 remaining planned cycles of chemotherapy, the chemotherapy cycles may be 3 or 4 weeks in duration, and the investigational product dose adjustment guidelines allow for up to 12 weeks of dosing before a subject is declared a non-responder, the majority of study subjects will receive investigational product for a range of 10-24 weeks.
Interventions
DRUGRomiplostim
This study is designed to study Romiplostim for the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients receiving chemotherapy for the treatment of non-small cell lung cancer (NSCLC), ovarian cancer, or breast cancer
DRUGPlacebo
Placebo comparator
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
The study will consist of a screening period of up to 4 weeks, a treatment period long enough to allow for assessment of 3 planned cycles of chemotherapy, a follow-up visit, and LTFU. Given that subjects are required to have 3 remaining planned cycles of chemotherapy, the chemotherapy cycles may be 3 or 4 weeks in duration, and the investigational product dose adjustment guidelines allow for up to 12 weeks of dosing before a subject is declared a non-responder, the majority of study subjects will receive investigational product for a range of 10-24 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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 greater than or equal to 18 years of age at signing of the informed consent. * Documented active stage I, II, III or IV locally advanced or metastatic of the following tumor types: NSCLC, breast cancer, or ovarian cancer (includes fallopian tube epithelial carcinomas and peritoneal epithelial carcinoma of unknown primary), or any stage recurrent disease. Patients with documented locally advanced (stage III) NSCLC should not be amenable to definitive treatment with chemoradiation and/or surgery. * Subjects must be receiving cancer treatment with 21- or 28-day cycles, using one of the following carboplatinum-based combination chemotherapy regimens: carboplatin/gemcitabine based, carboplatin/pemetrexed based, carboplatin/liposomal doxorubicin based or carboplatin/taxane based (which includes either paclitaxel, nab-paclitaxel, or docetaxel) or single agent chemotherapy regimen with any of the above mentioned drugs. Use of combination regimens with one of the above carboplatinum-based regimens is permitted with (1) anti-angiogenic agents (such as bevacizumab); (2) targeted therapy (such as anti-epidermal growth factor agents or anti- human epidermal growth factor receptor 2) or (3) immune checkpoint inhibitors. Cycle duration is based on intervals between day 1 of chemotherapy cycles (overlapping with carboplatin intervals) every 21 or 28 day cycles for single agent regimens. OR, Subjects must have CIT from a non-protocol chemotherapy regimen, planning to start treatment with one of the above protocol chemotherapy regimens which has been delayed ≥ 1 week due to CIT. * Subjects must have a local platelet count ≤ 85 x 109/L on day 1 of the study. * Subjects must be at least 21 or 28 days removed from the start of the chemotherapy cycle immediately prior to study day 1 if receiving a 21-day or 28-day cycle chemotherapy regimen, respectively. * 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
* 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 greater than 470 msec, pericardial disease, or myocardial infarction. * Major surgery less than or equal to 28 days or minor surgery less than or equal to 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 stable and suitable for continued therapeutic anticoagulation during trial participation. * History of arterial thrombotic events (eg, myocardial ischemia, transient ischemic attack, or stroke) within 6 months prior to screening. * Evidence of active infection within 2 weeks prior to the first dose of study treatment. * Known human immunodeficiency virus infection with any detectable viral load at screening. Subjects without a documented diagnosis in their medical history will require a local laboratory assessment at screening. If local laboratory results are not available use central laboratory results. * Known active of chronic hepatitis C or hepatitis B infection. Subjects without a documented diagnosis in their medical history will require a local laboratory assessment at screening. If local laboratory results are not available use central laboratory results. 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: hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C. * In addition to the conditions listed in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of either a chemotherapy dose delay or reduction | 48 days | No thrombocytopenia-induced modification of any myelosuppressive agent in the second and third cycles of the planned on-study chemotherapy regimen. Thrombocytopenia-induced modifications include chemotherapy dose reduction, delay, omission, or chemotherapy treatment discontinuation due to platelet counts below 100 x 109/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depth of Platelet Count | 48 days | the depth of the platelet count nadir from the start of the first on-study chemotherapy cycle through the end of the treatment period |
| Time to First platelet response | 7 days | The time to first platelet response, defined by platelet count ≥ 100 x 109/L in the absence of platelet transfusions during the preceding 7 days |
| the duration-adjusted event rate of ≥ grade 2 bleeding events | 48 days | the duration-adjusted event rate of ≥ grade 2 bleeding events, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading scale |
| Overall survival | 1 Year | 1-year overall survival |
| Proportion of subjects with at leat 1 incidence of platelet transfusion | 48 days | platelet transfusion(s) during the treatment period |
| proportion of patients achieving platelet count >= 100 x 10 9/L | 7 days | 7 days after 3rd dose of IP with no transfusions in preceding 7 days |
| The subject incidence of adverse events | 36 months | Through end of study, up to 36 months. It will be counted in as an adverse event: any treatment - emergent adverse events, fatal adverse events, serious adverse events, or clinically significant changes in laboratory values. |
| Number of subjects who develop anti-romiplostim antibodies | 36 Months | Through end of study up to 36 months |
| Number of subjects who develop anti-TPO antibodies | 36 months | Through end of study, up to 36 months |
| Number of subjects who experience myelodysplastic syndromes | 36 months | Through end of study, up to 36 months |
| Number of subjects who experience secondary malignancies | 36 months | Through end of study, up to 36 months |
Countries
Argentina, Austria, Brazil, Bulgaria, Chile, Colombia, Greece, Hungary, Mexico, Peru, Poland, Portugal, Romania, Russia, Spain, Turkey (Türkiye), Ukraine, United States
Contacts
STUDY_DIRECTORMD
Amgen
Outcome results
None listed