A Phase 2 Trial of AMG 706 or Bevacizumab in Combination With Chemo for Advanced NSCLC

NCT00369070 | Terminated Phase 2 DMC

• 1 other identifier: 20060136
• Study Type: interventional
• Target: 186
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to estimate the difference in objective response rates between each paclitaxel/carboplatin plus AMG 706 arm (Arm A and B) and paclitaxel/carboplatin plus bevacizumab arm (Arm C) in subjects with advanced non-squamous NSCLC.

Conditions

Advanced Non-squamous NSCLC

Keywords

AMG 706; Bevacizumab; Paclitaxel and Carboplatin; Randomized; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective tumor response rate

  Response assessments will be obtained every 6 +/- 1 week until subjects develop disease progression.

Secondary Outcomes (5)

• Duration of response

  Time from first objective tumor response to disease progression or death, if the death was due to disease progression.

• Progression free survival

  Number of days from randomization tot he date of radiological evidence of disease progression or death.

• Overall survival

  Time from randomization to death.

• Pharmacokinetics of AMG 706 when administered with paclitaxel and carboplatin in Arms A and B

  From randomization until disease progression or death.

• Safety and tolerability in the 3 arms

  From randomization until disease progression or death.

Study Arms (3)

A

EXPERIMENTAL

AMG 706 125 mg once daily (QD) and paclitaxel and carboplatin chemotherapy regimen (paclitaxel 200 mg/m2 and carboplatin at AUC of 6 mg/mL x min) on day 1 of each 3 week cycle for a maximum of 6 cycles.

Drug: AMG 706; Drug: Paclitaxel; Drug: Carboplatin

B

EXPERIMENTAL

AMG 706 75 mg twice daily every 12 ± approximately 1 hour for 5 days followed by a 2 day treatment free period every 7 days and paclitaxel and carboplatin chemotherapy regimen (paclitaxel 200 mg/m2 and carboplatin at AUC of 6 mg/mL x min) on day 1 of each 3 week cycle for a maximum of 6 cycles.

Drug: AMG 706; Drug: Paclitaxel; Drug: Carboplatin

C

ACTIVE COMPARATOR

Bevacizumab 15 mg/kg bevacizumab, delivered via intravenous (IV) infusion once every 3 weeks and paclitaxel and carboplatin chemotherapy regimen (paclitaxel 200 mg/m2 and carboplatin at AUC of 6 mg/mL x min) on day 1 of each 3 week cycle for a maximum of 6 cycles.

Biological: Bevacizumab; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Bevacizumab BIOLOGICAL

15 mg/kg bevacizumab, delivered via intravenous (IV) infusion once every 3 weeks

Also known as: Avastin

C

AMG 706 DRUG

subjects in Arms A and B will take AMG 706 orally in one of two dosing regimens over each 21-day cycle: •Arm A: 125 mg once daily (QD) •Arm B: 75 mg twice daily every 12 ± approximately 1 hour for 5 days followed by a 2 day treatment free period every 7 days

Also known as: Motesanib diphosphate

A; B

Paclitaxel DRUG

All subjects will receive a paclitaxel chemotherapy regimen (paclitaxel 200 mg/m2) on day 1 of each 3-week cycle for a maximum of 6 cycles.

A; B; C

Carboplatin DRUG

All subjects will receive carboplatin chemotherapy regimen (carboplatin at AUC of 6 mg/mL x min) on day 1 of each 3-week cycle for a maximum of 6 cycles.

A; B; C

Eligibility Criteria

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

You may qualify if:

• Men or women 18 years or older with histologically or cytologically confirmed advanced non-squamous NSCLC (unresectable stage IIIB with pericardial or pleural effusion or stage IV/recurrent)
• Measureable disease per RECIST criteria modified
• ECOG performance status of 0 or 1
• Ability to take oral medications
• Competent to give written informed consent

You may not qualify if:

• Current or prior history of CNS metastases
• Any prior chemotherapy for advanced NSCLC
• History of pulmonary hemorrhage or gross hemoptysis within 6 months prior to randomization
• Prior targeted therapies
• Known history of allergy or hypersensitivity to paclitaxel or carboplatin
• History of arterial or venous thrombosis within 52 weeks prior to randomization
• History of bleeding diathesis or non-pulmonary bleeding within 14 days prior to randomization
• Peripheral neuropathy \> grade 1 per CTCAE Version 3.0
• Myocardial infarction, cerebrovascular accident, grade 2 or greater peripheral vascular disease, transient ischemic attack, congestive heart failure, percutaneous transluminal coronary angioplasty/stent, ongoing arrythmias requiring medication or unstable angina within 52 weeks prior to randomization
• Any kind of disorder that compromises the ability of the subject to comply with the study procedures
• Uncontrolled hypertension as defined by resting blood pressure \> 150/90 mm Hg. Anti-hypertensive medications are allowed if hypertension is stably controlled at the time of randomization.
• Participation in therapeutic clinical trials or currently receiving other investigational treatment(s) within 30 days prior to randomization
• Pregnant or breast feeding women
• Known to be HIV, hepatitis B surface antigen, or hepatitis C positive

Sponsors & Collaborators

• Amgen: lead

Related Publications (3)

• Blumenschein GR Jr, Kabbinavar F, Menon H, Mok TSK, Stephenson J, Beck JT, Lakshmaiah K, Reckamp K, Hei YJ, Kracht K, Sun YN, Sikorski R, Schwartzberg L; Motesanib NSCLC Phase II Study Investigators. A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer. Ann Oncol. 2011 Sep;22(9):2057-2067. doi: 10.1093/annonc/mdq731. Epub 2011 Feb 14.

  PMID: 21321086 BACKGROUND

• Claret L, Lu JF, Bruno R, Hsu CP, Hei YJ, Sun YN. Simulations using a drug-disease modeling framework and phase II data predict phase III survival outcome in first-line non-small-cell lung cancer. Clin Pharmacol Ther. 2012 Nov;92(5):631-4. doi: 10.1038/clpt.2012.78. Epub 2012 Aug 22.

  PMID: 22910440 BACKGROUND

• Bass MB, Yao B, Hei YJ, Ye Y, Davis GJ, Davis MT, Kaesdorf BA, Chan SS, Patterson SD. Challenges in developing a validated biomarker for angiogenesis inhibitors: the motesanib experience. PLoS One. 2014 Oct 14;9(10):e108048. doi: 10.1371/journal.pone.0108048. eCollection 2014.

  PMID: 25314641 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab; motesanib diphosphate; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

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

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

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2006
• First Posted: August 29, 2006
• Study Start: January 31, 2007
• Primary Completion: April 23, 2008
• Study Completion: August 3, 2011
• Last Updated: January 4, 2018

Record last verified: 2018-01