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

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.

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Lung Neoplasms; Non-Small Cell Lung Cancer; Thrombocytopenia; Lung Cancer; Solid Tumors; Oncology; Chemotherapy-Induced Thrombocytopenia
• Intervention / Treatment: Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Drug: Placebo; Biological: Romiplostim

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Research Site
  • Graz, Austria
    • Research Site
  • Innsbruck, Austria, 6020
    • Research Site
  • Innsbruck, Austria
    • Research Site
  • Klagenfurt, Austria
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  • Klagenfurt, Austria, 9026
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  • Linz, Austria
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  • Linz, Austria, 4010
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  • Rankweil, Austria, 6830
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  • Rankweil, Austria
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  • Wien, Austria
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  • Wien, Austria, 1090
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• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
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    • Toronto, Ontario, Canada
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  • Quebec
    • Sainte-Foy, Quebec, Canada
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    • Sainte-Foy, Quebec, Canada, G1V 4G5
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• Germany
  • Bad Berka, Germany, 99437
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  • Bad Berka, Germany
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  • Dresden, Germany, 01307
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  • Dresden, Germany
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  • Halle/ Saale, Germany, 06120
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  • Halle/ Saale, Germany
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  • Hemer, Germany, 58675
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  • Hemer, Germany
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• Hungary
  • Budapest, Hungary
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  • Budapest, Hungary, 1125
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  • Budapest, Hungary, 1529
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  • Edeleny, Hungary, 3780
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  • Edeleny, Hungary
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  • Gyula, Hungary
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  • Gyula, Hungary, 5703
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  • Matrahaza, Hungary, 3233
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  • Matrahaza, Hungary
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  • Pecs, Hungary
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  • Pecs, Hungary, 7623
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  • Szekesfehervar, Hungary
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  • Szekesfehervar, Hungary, 8000
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  • Torokbalint, Hungary
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  • Torokbalint, Hungary, 2045
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  • Zalaegerszeg - Pozva, Hungary, 8900
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  • Zalaegerszeg - Pozva, Hungary
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• Ireland
  • Cork, Ireland
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  • Cork, Ireland, Cork
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  • Dublin, Ireland, 4
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  • Dublin, Ireland, 8
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  • Dublin, Ireland
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• Italy
  • Novara, Italy
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  • Novara, Italy, 28100
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  • Orbassano, Italy, 10043
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  • Orbassano, Italy
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  • Palermo, Italy
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  • Palermo, Italy, 90126
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  • Torino, Italy, 10126
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  • Torino, Italy
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• Portugal
  • Coimbra, Portugal
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  • Coimbra, Portugal, 3040-316
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  • Lisboa, Portugal
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  • Lisboa, Portugal, 1649-035
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  • Porto, Portugal, 4200-072
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  • Porto, Portugal
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  • Vila Nova de Gaia, Portugal
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  • Vila Nova de Gaia, Portugal, 4430-502
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• United States
  • Arizona
    • Glendale, Arizona, United States
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    • Glendale, Arizona, United States, 85304
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  • California
    • Anaheim, California, United States, 92801
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    • Anaheim, California, United States
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    • Los Angeles, California, United States
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    • Los Angeles, California, United States, 90048
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    • Rancho Mirage, California, United States
      • Research Site
    • Rancho Mirage, California, United States, 92270
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  • Florida
    • Boynton Beach, Florida, United States, 33435
      • Research Site
    • Boynton Beach, Florida, United States
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    • Vero Beach, Florida, United States
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    • Vero Beach, Florida, United States, 32960
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  • Georgia
    • Athens, Georgia, United States, 30607
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    • Athens, Georgia, United States
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    • Macon, Georgia, United States
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    • Macon, Georgia, United States, 31201
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  • Illinois
    • Peoria, Illinois, United States, 61615
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    • Peoria, Illinois, United States
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  • Iowa
    • Sioux City, Iowa, United States
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    • Sioux City, Iowa, United States, 51101
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  • Kentucky
    • Paducah, Kentucky, United States, 42003
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    • Paducah, Kentucky, United States
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  • Louisiana
    • Shreveport, Louisiana, United States
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    • Shreveport, Louisiana, United States, 71101
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  • Maryland
    • Baltimore, Maryland, United States
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    • Baltimore, Maryland, United States, 21201
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  • Michigan
    • Sterling Heights, Michigan, United States, 48314
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    • Sterling Heights, Michigan, United States
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  • Montana
    • Billings, Montana, United States, 59101
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    • Billings, Montana, United States
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  • New Jersey
    • Flemington, New Jersey, United States
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    • Flemington, New Jersey, United States, 08822
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  • New York
    • Johnson City, New York, United States, 13790
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    • Johnson City, New York, United States
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  • Oklahoma
    • Oklahoma City, Oklahoma, United States
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    • Oklahoma City, Oklahoma, United States, 73104
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  • Pennsylvania
    • Drexel Hill, Pennsylvania, United States
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    • Drexel Hill, Pennsylvania, United States, 19026
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    • Dunmore, Pennsylvania, United States
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    • Dunmore, Pennsylvania, United States, 18512
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    • Radnor, Pennsylvania, United States, 19087
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    • Radnor, Pennsylvania, United States
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  • South Carolina
    • Columbia, South Carolina, United States
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    • Columbia, South Carolina, United States, 29203
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  • Tennessee
    • Germantown, Tennessee, United States
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    • Germantown, Tennessee, United States, 38138
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  • Texas
    • Austin, Texas, United States, 78705
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    • Austin, Texas, United States
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    • Houston, Texas, United States, 77030
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    • Houston, Texas, United States, 77074
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    • Houston, Texas, United States
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Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Gemcitabine; Intravenous infusion; Drug: Cisplatin; Intravenous infusion; Drug: Carboplatin; Intravenous infusion; Drug: Placebo; Placebo subcutaneous injection.
Experimental: Romiplostim 250 μg; 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.	Drug: Gemcitabine; Intravenous infusion; Drug: Cisplatin; Intravenous infusion; Drug: Carboplatin; Intravenous infusion; Biological: Romiplostim; Romiplostim is a thrombopoiesis recombinant protein that targets the thrombopoietin (TPO) receptor which results in increased platelet production.; Other Names: Nplate®; AMG 531
Experimental: Romiplostim 500 μg; 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.	Drug: Gemcitabine; Intravenous infusion; Drug: Cisplatin; Intravenous infusion; Drug: Carboplatin; Intravenous infusion; Biological: Romiplostim; Romiplostim is a thrombopoiesis recombinant protein that targets the thrombopoietin (TPO) receptor which results in increased platelet production.; Other Names: Nplate®; AMG 531
Experimental: Romiplostim 750 μg; 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.	Drug: Gemcitabine; Intravenous infusion; Drug: Cisplatin; Intravenous infusion; Drug: Carboplatin; Intravenous infusion; Biological: Romiplostim; Romiplostim is a thrombopoiesis recombinant protein that targets the thrombopoietin (TPO) receptor which results in increased platelet production.; Other Names: Nplate®; AMG 531

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: December 15, 2006
• First Submitted That Met QC Criteria: December 15, 2006
• First Posted (Estimate): December 19, 2006

Study Record Updates

• Last Update Posted (Estimate): October 24, 2013
• Last Update Submitted That Met QC Criteria: September 18, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Gemcitabine; NSCLC; Cisplatin; Carboplatin; CIT; Advanced Non-Small Cell Lung Cancer; Chemotherapy Induced Thrombocytopenia; Stage IIIB NSCLC; Stage IV NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Hematologic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Blood Platelet Disorders; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Thrombocytopenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Carboplatin; Cisplatin
• Other Study ID Numbers: 20050154