Back to resultsStudy to Evaluate Motesanib With or Without Carboplatin/Paclitaxel or Panitumumab in the Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Primary Purpose
Lung Cancer, Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Panitumumab
Motesanib diphosphate
Paclitaxel
Carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Lung Cancer focused on measuring Lung cancer, Non-small cell lung cancer, NSCLC, Clinical Trial, Panitumumab, AMG 706, Anti-angiogenesis, Immunex, Abgenix, Amgen, Stage IIIB, Stage IV, Unresectable
Eligibility Criteria
Inclusion Criteria: Diagnosis of unresectable stage IIIB or IV non-small cell lung cancer (NSCLC) No more than one prior chemotherapy Adequate hematologic, renal and hepatic function Measurable disease or evaluable disease on CAT scan or MRI Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Able to fast for 10 hrs twice during the study - Able to tolerate oral medications Life expectancy of at least 3 months Exclusion Criteria: Symptomatic or untreated central nervous system metastases requiring current treatment History of arterial thrombosis within 1 year prior to enrollment Anticoagulant therapy, except for warfarin of less than 2mg per day Symptomatic peripheral neuropathy History of pulmonary hemorrhage or hemoptysis Myocardial infarction within 1 year before enrollment Uncontrolled hypertension [diastolic greater than 85 mmHg; systolic greater than 145 mmHg] History of other cancer, unless treated with no known active disease for longer than 3 years Previous treatment with AMG 706 or panitumumab, previous treatment with inhibitors of VEGF or EGF No antibody treatment for 6 weeks prior to enrollment Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Paclitaxel + Carboplatin + Motesanib
Panitumumab + Motesanib
Panitumumab + Paclitaxel + Carboplatin + Motesanib
Arm Description
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. The initial dose of motesanib was 50 mg once daily administered in the initial cohort and up to 125 mg once daily was used in subsequent cohorts. A cycle was defined as the 3 weeks plus the time to recover from toxicity, if encountered.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab administered by IV at 9.0 mg/kg on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. The initial dose of motesanib was 50 mg once daily administered in the initial cohort, up to 125 mg once daily was used in subsequent cohorts.
Chemotherapy naïve participants received panitumumab administered by IV at 9.0 mg/kg on Day 1 of each 21-day cycle, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants were enrolled in this arm once a safe and tolerable dose of motesanib was established.
Outcomes
Primary Outcome Measures
Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1
The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 1. For the 75 mg BID cohorts, Tmax is reported for the first daily dose.
Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1
The maximal observed plasma concentration of motesanib after a single dose dose in Cycle 1. For the 75 mg BID cohorts, Cmax is reported for the first daily dose.
Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1
The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose.
Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1
Area under the plasma concentration-time curve for motesanib in Cycle 1 calculated using the using the linear/log trapezoidal method. AUC from time zero to infinity (AUC0-inf) is reported for the 50 and 125 mg QD cohorts and AUC from time 0 to 24 hours post-dose (AUC0-24) is reported for the 75 mg BID cohort, where AUC0-24 is the sum of AUC0-12 for the first and second daily dose.
Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1
The trough plasma concentration for motesanib at 24 hours postdose in Cycle 1. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose).
Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2
The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 2. For the 75 mg BID cohorts, Tmax is reported for the first daily dose.
Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2
The maximal observed plasma concentration of motesanib in Cycle 2, after multiple doses. For the 75 mg BID cohorts, Cmax is reported for the first daily dose.
Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2
The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose.
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) for motesanib in Cycle 2 calculated using the using the linear/log trapezoidal method. For the 75 mg BID cohort AUC0-24 is the sum of AUC0-12 for the first and second daily dose.
Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2
The trough plasma concentration for motesanib at 24 hours postdose in Cycle 2. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose).
Secondary Outcome Measures
Percentage of Participants With an Overall Objective Response
Confirmed objective tumor response defined as a complete response (CR) or partial response (PR) using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Tumor response was evaluated by computed tomography (CT) scan or magnetic resonance imaging (MRI). Responding disease (CR or PR) was confirmed no less than 4 weeks after the criteria for response were first met. A complete response defined as the disappearance of all target lesions and all non-target lesions, no new lesions and normalization of tumor marker level. Partial response defined as either the disappearance of all target lesions and the persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diamer (LD) of target lesions, taking as reference the baseline sum LD and no new lesions and/or unequivocal progression of existing non-target lesions.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00094835
Brief Title
Study to Evaluate Motesanib With or Without Carboplatin/Paclitaxel or Panitumumab in the Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Official Title
An Open-label, Dose-finding Study to Evaluate the Safety and Pharmacokinetics (PK) of AMG 706 With Carboplatin/Paclitaxel, AMG 706 With Panitumumab and AMG 706 With Panitumumab and Carboplatin/Paclitaxel in the Treatment of Subjects With Advanced Non-Small Cell Lung Cancer (NSCLC)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
March 2007 (Actual)
Study Completion Date
March 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
5. Study Description
Brief Summary
The purpose of this trial is: - To characterize the safety profile of motesanib when used in combination with carboplatin/paclitaxel (CP), with panitumumab or with CP and panitumumab in patients with advanced non-small cell lung cancer (NSCLC). - To establish the pharmacokinetic (PK) profile of motesanib when it is used in combination with CP, with panitumumab, or with CP and panitumumab. - To compare the paclitaxel and motesanib PK profiles when the medications are administered 30 minutes (min) or approximately 48 hours (hrs) apart. - To characterize the panitumumab and paclitaxel exposure in the combination regimens of motesanib with CP, motesanib with panitumumab, or motesanib with CP and panitumumab. - To describe the objective response rate (ORR) in each dose cohort. - To measure the immunogenicity of panitumumab in patients administered motesanib with panitumumab and motesanib with CP and panitumumab.
Detailed Description
This was a multicenter, open-label, dose-finding clinical trial examining the safety and PK of once or twice daily motesanib administered with CP or with CP and panitumumab in chemotherapy naïve patients, and with panitumumab in patients with no more than one prior chemotherapy regimen for NSCLC.
Participants were enrolled into the Panitumumab + Paclitaxel + Carboplatin + Motesanib once a safe and tolerable dose of AMG 706 was established in the other treatment arms.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, Non-Small Cell Lung Cancer
Keywords
Lung cancer, Non-small cell lung cancer, NSCLC, Clinical Trial, Panitumumab, AMG 706, Anti-angiogenesis, Immunex, Abgenix, Amgen, Stage IIIB, Stage IV, Unresectable
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Paclitaxel + Carboplatin + Motesanib
Arm Type
Experimental
Arm Description
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. The initial dose of motesanib was 50 mg once daily administered in the initial cohort and up to 125 mg once daily was used in subsequent cohorts. A cycle was defined as the 3 weeks plus the time to recover from toxicity, if encountered.
Arm Title
Panitumumab + Motesanib
Arm Type
Experimental
Arm Description
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab administered by IV at 9.0 mg/kg on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. The initial dose of motesanib was 50 mg once daily administered in the initial cohort, up to 125 mg once daily was used in subsequent cohorts.
Arm Title
Panitumumab + Paclitaxel + Carboplatin + Motesanib
Arm Type
Experimental
Arm Description
Chemotherapy naïve participants received panitumumab administered by IV at 9.0 mg/kg on Day 1 of each 21-day cycle, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants were enrolled in this arm once a safe and tolerable dose of motesanib was established.
Intervention Type
Biological
Intervention Name(s)
Panitumumab
Other Intervention Name(s)
Vectibix, ABX-EGF
Intervention Description
9.0 mg/kg on Day 1 of each 21-day cycle administered by intravenous infusion over approximately 60 minutes.
Intervention Type
Drug
Intervention Name(s)
Motesanib diphosphate
Other Intervention Name(s)
AMG 706
Intervention Description
Dose-finding with an initial dose of 50 mg once daily and up to 125 mg once daily. 75 mg twice daily was also to be tested.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Paclitaxel 200 mg/m^2 administered by IV infusion over 3 hours.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin was administered IV over approximately 30 minutes. Carboplatin was dosed using the glomerular filtration rate (GFR) and Calvert formula to AUC/time curve of 6 mg/mL×min.
Primary Outcome Measure Information:
Title
Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1
Description
The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 1. For the 75 mg BID cohorts, Tmax is reported for the first daily dose.
Time Frame
Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Title
Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1
Description
The maximal observed plasma concentration of motesanib after a single dose dose in Cycle 1. For the 75 mg BID cohorts, Cmax is reported for the first daily dose.
Time Frame
Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Title
Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1
Description
The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose.
Time Frame
Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours postdose.
Title
Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1
Description
Area under the plasma concentration-time curve for motesanib in Cycle 1 calculated using the using the linear/log trapezoidal method. AUC from time zero to infinity (AUC0-inf) is reported for the 50 and 125 mg QD cohorts and AUC from time 0 to 24 hours post-dose (AUC0-24) is reported for the 75 mg BID cohort, where AUC0-24 is the sum of AUC0-12 for the first and second daily dose.
Time Frame
Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Title
Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1
Description
The trough plasma concentration for motesanib at 24 hours postdose in Cycle 1. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose).
Time Frame
Cycle 1, Day 3, 24 hours post-dose
Title
Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2
Description
The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 2. For the 75 mg BID cohorts, Tmax is reported for the first daily dose.
Time Frame
Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Title
Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2
Description
The maximal observed plasma concentration of motesanib in Cycle 2, after multiple doses. For the 75 mg BID cohorts, Cmax is reported for the first daily dose.
Time Frame
Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Title
Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2
Description
The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose.
Time Frame
Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Title
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2
Description
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) for motesanib in Cycle 2 calculated using the using the linear/log trapezoidal method. For the 75 mg BID cohort AUC0-24 is the sum of AUC0-12 for the first and second daily dose.
Time Frame
Cycle 2, Day 1 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Title
Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2
Description
The trough plasma concentration for motesanib at 24 hours postdose in Cycle 2. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose).
Time Frame
Cycle 2, Day 1, 24 hours post-dose
Secondary Outcome Measure Information:
Title
Percentage of Participants With an Overall Objective Response
Description
Confirmed objective tumor response defined as a complete response (CR) or partial response (PR) using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Tumor response was evaluated by computed tomography (CT) scan or magnetic resonance imaging (MRI). Responding disease (CR or PR) was confirmed no less than 4 weeks after the criteria for response were first met. A complete response defined as the disappearance of all target lesions and all non-target lesions, no new lesions and normalization of tumor marker level. Partial response defined as either the disappearance of all target lesions and the persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diamer (LD) of target lesions, taking as reference the baseline sum LD and no new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame
After 9 weeks of treatment (at the end of Cycle 3)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of unresectable stage IIIB or IV non-small cell lung cancer (NSCLC)
No more than one prior chemotherapy
Adequate hematologic, renal and hepatic function
Measurable disease or evaluable disease on CAT scan or MRI
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Able to fast for 10 hrs twice during the study - Able to tolerate oral medications
Life expectancy of at least 3 months
Exclusion Criteria:
Symptomatic or untreated central nervous system metastases requiring current treatment
History of arterial thrombosis within 1 year prior to enrollment
Anticoagulant therapy, except for warfarin of less than 2mg per day
Symptomatic peripheral neuropathy
History of pulmonary hemorrhage or hemoptysis
Myocardial infarction within 1 year before enrollment
Uncontrolled hypertension [diastolic greater than 85 mmHg; systolic greater than 145 mmHg]
History of other cancer, unless treated with no known active disease for longer than 3 years
Previous treatment with AMG 706 or panitumumab, previous treatment with inhibitors of VEGF or EGF
No antibody treatment for 6 weeks prior to enrollment
Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
20028752
Citation
Blumenschein GR Jr, Reckamp K, Stephenson GJ, O'Rourke T, Gladish G, McGreivy J, Sun YN, Ye Y, Parson M, Sandler A. Phase 1b study of motesanib, an oral angiogenesis inhibitor, in combination with carboplatin/paclitaxel and/or panitumumab for the treatment of advanced non-small cell lung cancer. Clin Cancer Res. 2010 Jan 1;16(1):279-90. doi: 10.1158/1078-0432.CCR-09-1675. Epub 2009 Dec 22.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Study to Evaluate Motesanib With or Without Carboplatin/Paclitaxel or Panitumumab in the Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
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