Clinical trial NCT00094835: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2004-10-27
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1
timeFrame: 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.
measure: Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1
timeFrame: 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.
measure: Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1
timeFrame: Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours postdose.
measure: Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1
timeFrame: 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.
measure: Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1
timeFrame: Cycle 1, Day 3, 24 hours post-dose
measure: Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2
timeFrame: 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.
measure: Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2
timeFrame: 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.
measure: Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2
timeFrame: 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.
measure: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2
timeFrame: 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.
measure: Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2
timeFrame: Cycle 2, Day 1, 24 hours post-dose
Secondary outcomes:
measure: Percentage of Participants With an Overall Objective Response
timeFrame: After 9 weeks of treatment (at the end of Cycle 3)
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
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.