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

Amgen

Status and phase: Completed; Phase 2; Phase 1

Conditions: Lung Cancer; Non-Small Cell Lung Cancer

Treatments: Drug: Motesanib diphosphate; Drug: Carboplatin; Biological: Panitumumab; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT00094835

20040153

Details and patient eligibility

About

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.

Full 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.

Enrollment: 51 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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51 participants in 3 patient groups

Paclitaxel + Carboplatin + Motesanib

Experimental group

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.

Treatment:

Drug: Carboplatin

Drug: Paclitaxel

Drug: Motesanib diphosphate

Panitumumab + Motesanib

Experimental group

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.

Treatment:

Biological: Panitumumab

Drug: Motesanib diphosphate

Panitumumab + Paclitaxel + Carboplatin + Motesanib

Experimental group

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.

Treatment:

Drug: Carboplatin

Drug: Paclitaxel

Biological: Panitumumab

Drug: Motesanib diphosphate