Phase 3 Randomized, Double-blind, Placebo-controlled Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Gastrointestinal, Pancreatic, or Colorectal Cancer

The primary objective of this study is to evaluate the **efficacy** of romiplostim in the treatment of **chemotherapy-induced thrombocytopenia** (CIT) in patients undergoing chemotherapy for gastrointestinal, pancreatic, or colorectal cancer. This is measured by the ability to administer on-time, full-dose chemotherapy, which is clinically relevant as it may improve treatment outcomes and reduce the risk of complications associated with delayed or reduced chemotherapy dosing.

Secondary objectives include:

• Comparing the treatment effect of romiplostim with placebo on the depth of platelet nadir.
• Assessing the time to first platelet response between romiplostim and placebo.
• Evaluating the incidence of ≥ grade 2 bleeding events with romiplostim versus placebo.
• Comparing overall survival rates between the two groups.
• Investigating the incidence of platelet transfusions required in each treatment group.
• Determining the proportion of patients achieving a platelet response with romiplostim compared to placebo.
• Assessing the overall safety profile of romiplostim.

The clinical trial involves a total of **94 participants** diagnosed with **chemotherapy-induced thrombocytopenia** in the context of gastrointestinal, pancreatic, or colorectal cancer. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on a confirmed histological or cytological diagnosis of adenocarcinoma in the specified cancer types, with no restrictions on tumor stage. The trial includes individuals receiving specific chemotherapy regimens, such as oxaliplatin-based treatments, and those experiencing treatment delays due to thrombocytopenia. Participants must have a local platelet count of 85 x 10⁹/L or lower on study day 1 and an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. The trial population is characterized by a vulnerable group, as defined by the inclusion of individuals with compromised health due to cancer and chemotherapy. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy of **romiplostim** in treating **chemotherapy-induced thrombocytopenia** in patients undergoing **oxaliplatin-based chemotherapy** for gastrointestinal, pancreatic, or colorectal cancer. The trial aims to assess the ability to administer on-time, full-dose chemotherapy without thrombocytopenia-induced modifications. The study is expected to run from July 3, 2019, to March 31, 2025, with participant involvement lasting up to 21 days, corresponding to the maximum treatment period with the investigational product.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, cancer diagnosis, and platelet count. Following successful screening, participants will be randomized to receive either romiplostim or placebo, administered subcutaneously. The primary endpoint is the absence of thrombocytopenia-induced modifications in the second and third cycles of chemotherapy. Secondary endpoints include the depth of the platelet count nadir, time to first platelet response, and overall survival.

Study visits will include regular follow-up assessments to monitor platelet counts, adverse events, and overall health status. The end-of-study visit will occur after the completion of the treatment period, where final evaluations will be conducted. Participants may be withdrawn from the study early if they experience severe adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The trial is conducted under strict ethical guidelines, ensuring informed consent is obtained from all participants or their legally acceptable representatives before any study-specific procedures are initiated.

The clinical trial involves the administration of **romiplostim**, marketed under the name Nplate, which is provided as a 500 micrograms powder and solvent for solution for injection. The pharmaceutical form is a solution for injection, and the active substance is classified as a protein of other origin. The medication is administered subcutaneously. The dosing regimen allows for a maximum daily dose of 10 micrograms per kilogram, with a total maximum dose of 210 micrograms per kilogram over a treatment period of 21 days. The product is manufactured by Amgen Europe B.V. and is identified by the sponsor product code AMG 531. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The study also includes a **placebo** control, which is provided in identical 5 mL single-use vials. The placebo is a sterile, white, preservative-free, lyophilized powder that contains histidine, mannitol, sucrose, and polysorbate 20. Upon reconstitution with sterile water for injection, the solution has a pH of 5.0. The placebo is designed to match the appearance and administration route of the experimental medication to maintain the double-blind nature of the study. Participant compliance with the placebo administration is similarly monitored to ensure the integrity of the trial results.

The efficacy of **romiplostim** in the treatment of chemotherapy-induced thrombocytopenia (CIT) will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the absence of thrombocytopenia-induced modifications in the chemotherapy regimen during the second and third cycles. These modifications include dose reduction, delay, omission, or discontinuation of chemotherapy due to platelet counts falling below 100 x 10⁹/L.

Secondary endpoints will provide additional insights into the efficacy of the treatment. These include the depth of the platelet count nadir from the start of the first on-study chemotherapy cycle through the end of the treatment period, and the time to first platelet response, defined by achieving a platelet count of ≥ 100 x 10⁹/L without platelet transfusions in the preceding 7 days. The duration-adjusted event rate of ≥ grade 2 bleeding events will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading scale. Other secondary endpoints include overall survival, the occurrence of platelet transfusions during the treatment period, and achieving a platelet count of ≥ 100 x 10⁹/L at any time from study day 1 to week 4, again without platelet transfusions in the preceding 7 days. Additionally, adverse events, including treatment-emergent, fatal, serious adverse events, and clinically significant changes in laboratory values, will be monitored, along with the presence of anti-romiplostim antibodies and antibodies to thrombopoietin (TPO), myelodysplastic syndromes, and secondary malignancies.