MONET1-MOtesanib NSCLC Efficacy and Tolerability Study

NCT00460317 | Terminated Phase 3 DMC

• 1 other identifier: 20050201
• Study Type: interventional
• Target: 1,450
• Locations: 0 countries
• Sites: N/A

Brief Summary

To determine if treatment with AMG 706 (motesanib diphosphate) in combination with paclitaxel and carboplatin improves overall survival compared to treatment with placebo in combination with paclitaxel and carboplatin in subjects with advanced non-squamous NSCLC and in subjects with adenocarcinoma histology (adenocarcinoma subpopulation).

Conditions

Non-Small Cell Lung Cancer

Keywords

lung; cancer; chemotherapy; paclitaxel; carboplatin; placebo; angiogenesis; VEGF; multi kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• Overall survival time. Time from randomization to death. Subjects who have not died while on study or are lost to follow up will be censored at their last contact date.

  Not able to be measured

Secondary Outcomes (8)

• Duration of response (calculated for only those subjects who respond)

  Time from first objective tumour response to objective disease progression or death due to any cause.

• Pharmacokinetics of AMG 706 when administered in combination with paclitaxel and carboplatin.

  Throughout the duration the patient is in the study.

• Association of AMG 706 treatment-induced PlGF increase with OS in subjects with non-squamous NSCLC and in subjects with adenocarcinoma histology

  Overall survival time in the PlGF analysis set

• Evaluation of OS, PFS, AMG 706 treatment-induced PlGF increase association with OS, ORR (only in subjects with measurable disease) and duration of response in subjects with non-squamous, non-adenocarcinoma histology

  OS, ORR and duration of response in the PlGF analysis set

• Evaluation of the pharmacokinetics of AMG 706 and metabolites when administered with paclitaxel and carboplatin (in approximately 250 subjects at selected centers)

  Carboplatin PK samples drawn from subjects at Cycle 3 and Cycle 5

Study Arms (2)

Arm B

PLACEBO COMPARATOR

All subjects on this treatment arm will receive a standard paclitaxel and carboplatin chemotherapy regimen (paclitaxel 200mg/m2 and carboplatin at AUC of 6mg/mL x min by Calvert formula) on day 1 of each 3 week cycle + - 3 days for a maximum of 6 cycles and placebo 125mg QD orally

Drug: placebo; Drug: paclitaxel; Drug: carboplatin

Arm A

ACTIVE COMPARATOR

All subjects on this treatment arm will receive a standard paclitaxel and carboplatin chemotherapy regimen (paclitaxel 200mg/m2 and carboplatin at AUC of 6mg/mL x min by Calvert formula) on day 1 of each 3 week cycle + - 3 days for a maximum of 6 cycles and AMG 706 125mg QD orally.

Drug: AMG 706; Drug: paclitaxel; Drug: carboplatin

Interventions

AMG 706 DRUG

125 mg QD orally every day

Arm A

placebo DRUG

125 mg QD orally every day

Arm B

paclitaxel DRUG

200mg/m2 on day 1 of each 3 week cycle +/- 3 days for a max of 6 cycles

Arm A; Arm B

carboplatin DRUG

AUC of 600mg/mL x min by Calvert formula on day 1 of each 3 week cycle +/- 3 days for a max of 6 cycles

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed, unresectable stage 111B with pericardial or pleural effusion or stage IV or recurrent non squamous NSCLC.
• Measurable or non-measurable disease per modified RECIST criteria
• ECOG performance status of 0 or 1
• Life expectancy of greater than or equal to 3 months as documented by the investigator
• ability to take oral medications
• competency to give written informed consent
• able to start protocol directed therapy within 7 days from date of randomization
• Hematological function, as follows:
• Absolute neutrophil count (ANC) \> = 1.5 x 109/L
• Platelet count \> = 100 x 109/L and \< = 850 x 109/L
• Hemoglobin \> =9 g/dL
• Renal function, as follows:
• Creatinine clearance \> 40 mL/min (calculated by Cockcroft Gault formula)
• Urinary protein quantitative value of \< = 30 mg in urinalysis or \< = 1+ on dipstick unless quantitative protein is \< 500 mg in a 24 hour urine sample
• Hepatic function, as follows:

You may not qualify if:

• Subjects with adenosquamous histology or an unclear histology subtype (eg, not otherwise specified) containing greater than 10% squamous cells
• untreated or symptomatic central nervous system metastases. Subjects with a history of brain metastases are eligible if definitive therapy has been administered (surgery and/or radiation therapy), there is no planned treatment for brain metastases, and the subject is clinically stable and is off corticosteroids for at least 2 weeks prior to randomization.
• Prior chemotherapy as follows: Any prior chemotherapy for advanced non squamous NSCLC
• Any prior adjuvant chemotherapy for non squamous NSCLC within 52 weeks prior to randomization. Adjuvant chemotherapy completed \> 52 weeks prior to randomization is permitted. Any prior chemoradiation for locally advanced stage III disease.
• Prior (within 30 days of randomization) yellow fever vaccination.
• Central (chest) radiation therapy within 28 days prior to randomization, radiation therapy within 14 days prior to randomization for peripheral lesions.
• History of pulmonary hemorrhage or gross hemoptysis (approximately 3 mL of bright red blood or more) within 6 months prior to randomization.
• Prior targeted therapies, including but not limited to:
• AMG 706, inhibitors of VEGF (eg, SU5416, SU6668, ZD6474, SU11248, PTK787, AZD2171, AEE 788, sorafenib, bevacizumab), or EGFr (eg, panitumumab, cetuximab, gefitinib, erlotinib).
• Known history of allergy or hypersensitivity reaction to paclitaxel or carboplatin.
• Any anticoagulation therapy within 7 days prior to randomization. The use of low-dose warfarin \[ \< = 2 mg daily\] or low molecular weight heparin or heparin flushes for prophylaxis against central venous catheter thrombosis is allowed.
• History of arterial or venous thrombosis within 12 months prior to randomization.
• History of bleeding diathesis or bleeding within 14 days prior to randomization.
• Peripheral neuropathy \> grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
• Clinically significant cardiac disease within 12 months of randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, congestive heart failure, or ongoing arrhythmias requiring medication.

Sponsors & Collaborators

• Amgen: lead
• Takeda: collaborator

Related Publications (4)

• Scagliotti GV, Vynnychenko I, Park K, Ichinose Y, Kubota K, Blackhall F, Pirker R, Galiulin R, Ciuleanu TE, Sydorenko O, Dediu M, Papai-Szekely Z, Banaclocha NM, McCoy S, Yao B, Hei YJ, Galimi F, Spigel DR. International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1. J Clin Oncol. 2012 Aug 10;30(23):2829-36. doi: 10.1200/JCO.2011.41.4987. Epub 2012 Jul 2.

  PMID: 22753922 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 BACKGROUND

• Novello S, Scagliotti GV, Sydorenko O, Vynnychenko I, Volovat C, Schneider CP, Blackhall F, McCoy S, Hei YJ, Spigel DR. Motesanib plus carboplatin/paclitaxel in patients with advanced squamous non-small-cell lung cancer: results from the randomized controlled MONET1 study. J Thorac Oncol. 2014 Aug;9(8):1154-61. doi: 10.1097/JTO.0000000000000227.

  PMID: 25157768 BACKGROUND

• Kubota K, Ichinose Y, Scagliotti G, Spigel D, Kim JH, Shinkai T, Takeda K, Kim SW, Hsia TC, Li RK, Tiangco BJ, Yau S, Lim WT, Yao B, Hei YJ, Park K. Phase III study (MONET1) of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC): Asian subgroup analysis. Ann Oncol. 2014 Feb;25(2):529-36. doi: 10.1093/annonc/mdt552. Epub 2014 Jan 13.

  PMID: 24419239 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

motesanib diphosphate; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2007
• First Posted: April 13, 2007
• Study Start: July 1, 2007
• Primary Completion: March 1, 2011
• Study Completion: August 1, 2013
• Last Updated: September 7, 2015

Record last verified: 2015-08