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

Amgen

Status and phase: Completed; Phase 2

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

Treatments: Drug: Carboplatin; Biological: Romiplostim; Drug: Placebo; Drug: Gemcitabine; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00413283

20050154

Details and patient eligibility

About

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.

Enrollment: 63 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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63 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Placebo

Drug: Cisplatin

Drug: Gemcitabine

Romiplostim 250 μg

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Cisplatin

Drug: Gemcitabine

Biological: Romiplostim

Romiplostim 500 μg

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Cisplatin

Drug: Gemcitabine

Biological: Romiplostim

Romiplostim 750 μg

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Cisplatin

Drug: Gemcitabine

Biological: Romiplostim