Study to Evaluate Motesanib With or Without Carboplatin/Paclitaxel or Panitumumab in the Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

NCT ID: NCT00094835

Last Updated: 2016-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2007-03-31

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.

Conditions

Lung Cancer; Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Paclitaxel + Carboplatin + Motesanib

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.

Group Type: EXPERIMENTAL

Motesanib diphosphate

Intervention Type: DRUG

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.

Paclitaxel

Intervention Type: DRUG

Paclitaxel 200 mg/m\^2 administered by IV infusion over 3 hours.

Carboplatin

Intervention Type: DRUG

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.

Panitumumab + Motesanib

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.

Group Type: EXPERIMENTAL

Panitumumab

Intervention Type: BIOLOGICAL

9.0 mg/kg on Day 1 of each 21-day cycle administered by intravenous infusion over approximately 60 minutes.

Motesanib diphosphate

Intervention Type: DRUG

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.

Panitumumab + Paclitaxel + Carboplatin + Motesanib

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.

Group Type: EXPERIMENTAL

Panitumumab

Intervention Type: BIOLOGICAL

9.0 mg/kg on Day 1 of each 21-day cycle administered by intravenous infusion over approximately 60 minutes.

Motesanib diphosphate

Intervention Type: DRUG

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.

Paclitaxel

Intervention Type: DRUG

Paclitaxel 200 mg/m\^2 administered by IV infusion over 3 hours.

Carboplatin

Intervention Type: DRUG

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.

Interventions

Panitumumab

9.0 mg/kg on Day 1 of each 21-day cycle administered by intravenous infusion over approximately 60 minutes.

Intervention Type: BIOLOGICAL

Motesanib diphosphate

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

Paclitaxel

Paclitaxel 200 mg/m\^2 administered by IV infusion over 3 hours.

Intervention Type: DRUG

Carboplatin

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.

Intervention Type: DRUG

Other Intervention Names

Vectibix; ABX-EGF; AMG 706

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

References

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.

Reference Type: BACKGROUND

PMID: 20028752 (View on PubMed)

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20040153

Identifier Type: -

Identifier Source: org_study_id

NCT00107224

Identifier Type: -

Identifier Source: nct_alias