Dose/ Schedule Finding Trial of Romiplostim for Chemotherapy-Induced Thrombocytopenia (CIT) in Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The purpose of this study is to identify an effective, well tolerated dose and schedule of romiplostim that is appropriate for the treatment of chemotherapy induced thrombocytopenia (CIT) in patients with non-small cell lung cancer receiving gemcitabine and platinum.

Official Title
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Phase 2, Randomized, Double Blind, Placebo-Controlled Dose and Schedule Finding Trial to Evaluate the Safety and Efficacy of AMG 531 For Treatment of Chemotherapy-Induced Thrombocytopenia in Subjects With Advanced Non-Small Cell Lung Cancer Already Receiving Gemcitabine and Platinum.

Conditions
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Lung Cancer, Chemotherapy-Induced Thrombocytopenia, Non-Small Cell Lung Cancer, Cancer, Lung Neoplasms, Oncology, Solid Tumors, Thrombocytopenia

Intervention / Treatment
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* Biological: Romiplostim
* Drug: Placebo
* Drug: Gemcitabine
* Drug: Carboplatin
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed locally advanced or metastatic stage IIIB or stage IV NSCLC receiving 21-day cycles of gemcitabine/carboplatin or gemcitabine/cisplatin Life expectancy ≥ 12 weeks at the time of screening Thrombocytopenia as evidenced by a platelet count ≤ 50 x 10^9/L during the qualifying cycle of chemotherapy, OR platelet count < 100 x 10^9/L on Day 22 of the qualifying cycle (for eligibility inclusion: ability to receive the same dose of chemotherapy on study), this criteria ensures that the patient must be dose delayed for platelet recovery Ability to receive the same dose and schedule of chemotherapy during the first on-study treatment cycle as was given in the qualifying cycle (except Day 8 gemcitabine) Absolute neutrophil count (ANC) ≥ 1,000/µL, hemoglobin ≥ 9.5 g/dL, and platelet count ≥ 100 x 10 ^9/L on Day 1 of the first on study chemotherapy treatment cycle Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at the time of screening Adequate Liver function; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN) (except for patients with a confirmed diagnosis of Gilbert's Syndrome) Adequate renal function; serum creatinine < 1.5 x ULN Exclusion Criteria: Receipt of > 1 prior systemic chemotherapy regimen Sepsis, disseminated coagulation or any other condition (i.e. immune [idiopathic] thrombocytopenic purpura [ITP], thrombotic thrombocytopenic purpura [TTP], hemolytic uremic syndrome [HUS]) that may exacerbate thrombocytopenia History of unstable angina, congestive heart failure, uncontrolled hypertension (diastolic > 100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year of screening ) myocardial infarction History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 1 year of screening History of pulmonary embolism or other venous thrombosis within 1 year of screening (except for catheter-related clots) Use of any nitrosourea or mitomycin-C within 6 weeks of screening Have received any thrombopoietic growth factor or related substance Have received granulocyte macrophage colony stimulating factor (GM-CSF) within the last 4 weeks prior to screening Have received any experimental therapy within 4 weeks prior to screening Have ever received a bone marrow or peripheral blood stem cell infusion (within 1 year of screening) Known hypersensitivity to any recombinant E. coli-derived product.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received a placebo subcutaneous injection on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice. | Drug: Placebo<br>* Placebo subcutaneous injection.<br>Drug: Gemcitabine<br>* Intravenous infusion<br>Drug: Carboplatin<br>* Intravenous infusion<br>Drug: Cisplatin<br>* Intravenous infusion<br>|
| Experimental: Romiplostim 250 μg<br>Participants received romiplostim 250 μg administered subcutaneously on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice. | Biological: Romiplostim<br>* Romiplostim is a thrombopoiesis recombinant protein that targets the thrombopoietin (TPO) receptor which results in increased platelet production.<br>* Other names: Nplate®;Drug: Gemcitabine<br>* Intravenous infusion<br>Drug: Carboplatin<br>* Intravenous infusion<br>Drug: Cisplatin<br>* Intravenous infusion<br>|
| Experimental: Romiplostim 500 μg<br>Participants received romiplostim 500 μg administered subcutaneously on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice. | Biological: Romiplostim<br>* Romiplostim is a thrombopoiesis recombinant protein that targets the thrombopoietin (TPO) receptor which results in increased platelet production.<br>* Other names: Nplate®;Drug: Gemcitabine<br>* Intravenous infusion<br>Drug: Carboplatin<br>* Intravenous infusion<br>Drug: Cisplatin<br>* Intravenous infusion<br>|
| Experimental: Romiplostim 750 μg<br>Participants received romiplostim 750 μg administered subcutaneously on Day 2 of each chemotherapy cycle. Chemotherapy consisted of 21-day cycles of gemcitabine/carboplatin (gemcitabine and carboplatin on Day 1 and gemcitabine again on Day 8) or 21-day cycles of gemcitabine/cisplatin (gemcitabine and cisplatin on Day 1 and gemcitabine again on Day 8), up to a maximum of 5 cycles administered according to standard institutional practice. | Biological: Romiplostim<br>* Romiplostim is a thrombopoiesis recombinant protein that targets the thrombopoietin (TPO) receptor which results in increased platelet production.<br>* Other names: Nplate®;Drug: Gemcitabine<br>* Intravenous infusion<br>Drug: Carboplatin<br>* Intravenous infusion<br>Drug: Cisplatin<br>* Intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | This summary includes all treatment-emergent adverse events recorded from the start of investigational product on this study, or any worsening of adverse events initially experienced before initiation of this study. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Grade 3 or 4 Thrombocytopenia | The duration of grade 3 or 4 thrombocytopenia (defined as platelet count <50 x 10^9/L) experienced during the first on study chemotherapy cycle by treatment group. | 3 weeks | 
| Number of Participants Experiencing Grade 3 or 4 Thrombocytopenia During the First Treatment Cycle. | The number of participants in each treatment group with grade 3 or 4 thrombocytopenia during the first on study treatment cycle. Per the Common Terminology Criteria for Adverse Events (CTCAE) v3.0, participants with a platelet count < 50 x 10^9/L, but ≥ 25 x 10^9/L are considered to have Grade 3 thrombocytopenia and participants with a platelet count < 25 x 10^9/L are considered to have Grade 4 thrombocytopenia. Additionally, participants with a platelet transfusion during the first on-study treatment cycle were classified as having Grade 3/4 thrombocytopenia. | 3 weeks | 
| Number of Participants With Platelet Transfusions | Number of participants who were administered platelet transfusions during first on study treatment cycle. | 3 weeks | 
| Platelet Count on Day 22 | Platelet count on Day 22 of the first on study chemotherapy treatment cycle (planned Day 1 of next cycle) by treatment group | Day 22 | 
| Gemcitabine Dose Reduction on Day 8 of the First Chemotherapy Cycle | Number of participants who required a gemcitabine dose reduction on Day 8 of the first on study chemotherapy cycle. | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Non-Small Cell Lung Cancer, Chemotherapy Induced Thrombocytopenia, CIT, NSCLC, Stage IIIB NSCLC, Stage IV NSCLC, Gemcitabine, Carboplatin, Cisplatin