MONET1-MOtesanib NSCLC Efficacy and Tolerability Study

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial of AMG 706 in Combination With Paclitaxel and Carboplatin for Advanced Non-small Cell Lung Cancer.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00460317
• Other study ID #: 20050201
• Status: Terminated
• Phase: Phase 3
• First received: April 12, 2007
• Last updated: August 24, 2015
• Start date: July 2007
• Est. completion date: August 2013

Study information

• Verified date: August 2015
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food & Drug AdministrationSpain: Spanish Drug AgencyTaiwan: Taiwan Provincial Department of HealthTurkey: Ministry of HealthUkraine: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug AdministrationAustria: Secretariat of HealthBrazil: Ministry of HealthCanada: Health CanadaChile: Health MinistryCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyFrance: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesGreece: National Organization for MedicinesHong Kong: Department of HealthArgentina: Ministry of HealthAustralia: Therapeutic Goods AdministrationHungary: National Institute of PharmacyIndia: Central Drugs Standard Control OrganizationIreland: Irish Medicines BoardIsrael: Ministry of HealthItaly: Ministry of HealthLithuania: State Medicines Control Agency of LithuaniaMexico: Ministry of HealthNetherlands: Medicines Evaluation BoardPhillippines: the Bureau of Food and DrugsPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Ministry of HealthSingapore: Health Science AuthoritySlovakia: Ministry of Health
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1450
• Est. completion date: August 2013
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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:

• Aspartate aminotransferase (AST) < =2.5 x upper limit of normal (ULN) OR AST < 5 x ULN if liver metastases are present

• Alanine aminotransferase (ALT) < =2.5 x ULN OR ALT < 5 x ULN if liver metastases are present

• Alkaline phosphatase < = 2.0 x ULN OR alkaline phosphatase < 5 x ULN if liver or bone metastases are present

• Total bilirubin < 1.5 x ULN OR total bilirubin < 3 X ULN if subject has UGT1A1 promoter polymorphism (ie, Gilbert syndrome) confirmed by genotyping or Invader UGT1A1 Molecular Assay prior to randomization Partial thromboplastin (PTT) or activated partial thromboplastin time (aPTT) < = 1 x ULN and international normalized ratio (INR) < = 1.5 x ULN

Exclusion Criteria:

• 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.

• History of other primary cancer unless: Curatively resected non melanomatous skin cancer. Curatively treated cervical carcinoma in situ. Other primary solid tumor curatively treated with no known active disease present and no curative treatment administered for the last 3 years

• Any kind of disorder that compromises the ability of the subject to comply with the study procedures.

• Open wound, ulcer or fracture.

• Uncontrolled hypertension as defined by resting blood pressure > 150/90 mm Hg. Antihypertensive medications are allowed if the subject is stable on their current dose at the time of randomization.

• Surgery:

• Major surgical procedures within 28 days prior to randomization

• Minor surgical procedures within 14 days prior to randomization

• Failure to recover from prior surgery

• Placement of a central venous access device (including ports and tunneled or non-tunneled catheters) within 7 days prior to randomization

• Planned elective surgery while on study treatment

• Core needle biopsy within 7 days prior to randomization

• Not recovered from all previous therapies (ie, radiation, surgery and medications). Adverse events related to previous therapies must be CTCAE grade < = 1 at screening or returned to the subject's baseline prior to their most recent previous therapy.

• Participation in therapeutic clinical trials or currently receiving other investigational treatment(s) within 30 days prior to randomization.

• Pregnant (eg, positive HCG test-serum or urine) or breast feeding woman.

• Any subject not consenting to use adequate contraceptive precautions (eg, hormonal, barrier or abstinence) during the course of the study and for 6 months after the last treatment.

• Known to be human immunodeficiency virus (HIV), hepatitis B surface antigen or hepatitis C positive.

• Known chronic hepatitis.

• Active infection requiring systemic treatment or any uncontrolled infection < = 14 days prior to randomization.

• History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results.

• Previously randomized to this study.

• Not available for follow-up assessments or unable to comply with study requirements.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-Small Cell Lung Cancer

Intervention

Drug:
• AMG 706
125 mg QD orally every day
• placebo
125 mg QD orally every day
• paclitaxel
200mg/m2 on day 1 of each 3 week cycle +/- 3 days for a max of 6 cycles
• carboplatin
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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Amgen	Takeda

References & Publications (3)

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. Erratum in: PLoS One. 2015;10(3):e0121162. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	No
Secondary	Pharmacokinetics of AMG 706 when administered in combination with paclitaxel and carboplatin.		Throughout the duration the patient is in the study.	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Safety and tolerability of AMG 706 in combination with paclitaxel and carboplatin compared to placebo in combination with paclitaxel and carboplatin in subjects with non-squamous NSCLC histology and in subjects with adenocarcinoma histology.		Throughout the duration the patient is in the study	Yes
Secondary	Progression free survival time: Subjects who have not progressed or died on study will be censored at their last evaluable assessment date.		Time from randomization to objective disease progression or death due to any cause	No
Secondary	Objective tumour response rate (complete and partial response) according to modified RECIST criteria in subjects with measurable disease at baseline.			No

External Links

•   AmgenTrials clinical trials website