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

NCT00094835 | Completed Phase 1 Results

• 1 other identifier: 20040153
• Study Type: interventional
• Target: 51
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (10)

• 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.

  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.

• 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.

  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.

• 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.

  Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours postdose.

• 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.

  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.

• 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).

  Cycle 1, Day 3, 24 hours post-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.

  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.

• 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.

  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.

• 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.

  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.

• 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.

  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.

• 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).

  Cycle 2, Day 1, 24 hours post-dose

Secondary Outcomes (1)

• Percentage of Participants With an Overall Objective Response

  After 9 weeks of treatment (at the end of Cycle 3)

Study Arms (3)

Paclitaxel + Carboplatin + Motesanib

EXPERIMENTAL

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.

Drug: Motesanib diphosphate; Drug: Paclitaxel; Drug: Carboplatin

Panitumumab + Motesanib

EXPERIMENTAL

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.

Biological: Panitumumab; Drug: Motesanib diphosphate

Panitumumab + Paclitaxel + Carboplatin + Motesanib

EXPERIMENTAL

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.

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

Interventions

Panitumumab BIOLOGICAL

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

Also known as: Vectibix, ABX-EGF

Panitumumab + Motesanib; Panitumumab + Paclitaxel + Carboplatin + Motesanib

Motesanib diphosphate 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.

Also known as: AMG 706

Paclitaxel + Carboplatin + Motesanib; Panitumumab + Motesanib; Panitumumab + Paclitaxel + Carboplatin + Motesanib

Paclitaxel DRUG

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

Paclitaxel + Carboplatin + Motesanib; Panitumumab + Paclitaxel + Carboplatin + Motesanib

Carboplatin 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.

Paclitaxel + Carboplatin + Motesanib; Panitumumab + Paclitaxel + Carboplatin + Motesanib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• 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.

  PMID: 20028752 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Panitumumab; motesanib diphosphate; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2004
• First Posted: October 27, 2004
• Study Start: January 1, 2005
• Primary Completion: March 1, 2007
• Study Completion: March 1, 2007
• Last Updated: March 24, 2016
• Results First Posted: March 24, 2014

Record last verified: 2016-02