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

Phase 2

Completed

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

Interventions: Drug: Placebo
Biological: Romiplostim
Drug: Gemcitabine
Drug: Carboplatin
Drug: Cisplatin

Registration Number: NCT00413283

Lead Sponsor: Amgen

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 63

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
Placebo	Gemcitabine	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.
Romiplostim 500 μg	Romiplostim	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.
Romiplostim 250 μg	Romiplostim	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.
Romiplostim 750 μg	Romiplostim	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.
Placebo	Cisplatin	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.
Placebo	Carboplatin	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.
Romiplostim 250 μg	Gemcitabine	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.
Romiplostim 250 μg	Carboplatin	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.
Romiplostim 250 μg	Cisplatin	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.
Romiplostim 500 μg	Carboplatin	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.
Romiplostim 500 μg	Gemcitabine	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.
Romiplostim 500 μg	Cisplatin	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.
Romiplostim 750 μg	Gemcitabine	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.
Romiplostim 750 μg	Carboplatin	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.
Romiplostim 750 μg	Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	4 months	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Platelet Transfusions	3 weeks	Number of participants who were administered platelet transfusions during first on study treatment cycle.
Duration of Grade 3 or 4 Thrombocytopenia	3 weeks	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.
Number of Participants Experiencing Grade 3 or 4 Thrombocytopenia During the First Treatment Cycle.	3 weeks	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.
Platelet Count on Day 22	Day 22	Platelet count on Day 22 of the first on study chemotherapy treatment cycle (planned Day 1 of next cycle) by treatment group
Gemcitabine Dose Reduction on Day 8 of the First Chemotherapy Cycle	8 days	Number of participants who required a gemcitabine dose reduction on Day 8 of the first on study chemotherapy cycle.