Safety Of AMG 706 Plus Panitumumab Plus Gemcitabine-Cisplatin In The Treatment Of Patients With Advanced Cancer

Study Overview

Safety of AMG 706 Plus Panitumumab Plus Gemcitabine-Cisplatin in the Treatment of Patients With Advanced Cancer

The purpose of this study is to characterize the safety and tolerability of AMG 706 plus panitumumab when administered with gemcitabine and cisplatin chemotherapy. This is a Phase 1b clinical study.

N/A

Lung Cancer
Pancreatic Cancer
Esophageal Cancer

DRUG: AMG 706
BIOLOGICAL: Panitumumab
DRUG: Gemcitabine
DRUG: Cisplatin

20040206

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2005-01-18	Results First Submitted 2010-08-13	Last Update Submitted that met QC Criteria 2014-02-03
First Submitted that Met QC Criteria 2005-01-18	Results First Submitted that Met QC Criteria 2014-02-03	Last Update Posted (ESTIMATED) 2014-03-20
First Posted (ESTIMATED) 2005-01-19	Results First Posted 2014-03-20	Last Verified 2014-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Panitumumab + Gem/Cis Panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle.	DRUG: AMG 706 AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1. BIOLOGICAL: Panitumumab Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle. DRUG: Gemcitabine Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2. DRUG: Cisplatin Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
EXPERIMENTAL: 50 mg QD AMG 706 + panitumumab + Gem/Cis AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle.	DRUG: AMG 706 AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1. BIOLOGICAL: Panitumumab Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle. DRUG: Gemcitabine Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2. DRUG: Cisplatin Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
EXPERIMENTAL: 75 mg QD AMG 706 + panitumumab + Gem/Cis AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle.	DRUG: AMG 706 AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1. BIOLOGICAL: Panitumumab Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle. DRUG: Gemcitabine Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2. DRUG: Cisplatin Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
EXPERIMENTAL: 100 mg QD AMG 706 + panitumumab + Gem/Cis AMG 706 100 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle.	DRUG: AMG 706 AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1. BIOLOGICAL: Panitumumab Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle. DRUG: Gemcitabine Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2. DRUG: Cisplatin Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
EXPERIMENTAL: 125 mg QD AMG 706 + panitumumab + Gem/Cis AMG 706 125 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle.	DRUG: AMG 706 AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1. BIOLOGICAL: Panitumumab Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle. DRUG: Gemcitabine Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2. DRUG: Cisplatin Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
EXPERIMENTAL: 75 mg BID AMG 706 + panitumumab + Gem/Cis AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle.	DRUG: AMG 706 AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1. BIOLOGICAL: Panitumumab Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle. DRUG: Gemcitabine Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2. DRUG: Cisplatin Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.

Primary Outcome Measures	Measure Description	Time Frame
Participant Incidence of Adverse Events	The number of participants who experienced at least one treatment-emergent adverse event. Additional details regarding specfic adverse events are provided in the Adverse Event section of this posting.	From the first dose of any study treatment until 30 days after the last dose of study treatment, up to a maximum of 509 days.

Secondary Outcome Measures	Measure Description	Time Frame
Number of Participants With an Objective Tumor Response	The number of participants with a confirmed objective tumor response, defined as a complete response (CR) or partial response (PR) throughout based on modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Any CR or PR was to be confirmed 4 to 6 weeks after the initial CR or PR.	From enrollment until date of last follow-up visit. The median follow-up time was 24 weeks, with a range of 3 to 73 weeks.
Tmax	Time after dosing when maximum plasma concentration was observed for AMG 706	Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.
Cmax	The maximum observed plasma concentration after AMG 706 dosing	Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.
AUC0-24	Area under the plasma concentration-time curve from time 0 to 24 hours postdose (AUC0-24) with AMG 706. AUC0-24 was estimated using the linear/log trapezoidal method. For the BID cohort, AUC0 24 was estimated as 2 times the AUC from time 0 to 12 hours post the first daily dose (AUC0-12) using the linear/log trapezoidal method.	Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.
AUC0-inf	Area under the concentration-time curve from time 0 to infinite time (AUC0-inf) postdose with AMG 706. AUC0-inf was estimated using the linear/log trapezoidal method. AUC0-inf was not calculated for the BID cohort.	Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Competent to comprehend, sign, and date an Institutional Review Board (IRB) approved informed consent form
Subjects with advanced cancer in whom the gemcitabine and cisplatin chemotherapy regimen is clinically indicated
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate hematological function
Adequate renal function
Adequate hepatic function
Life expectancy of greater than or equal to 3 months as documented by the investigator

More than 1 prior chemotherapy regimen
History of venous thrombosis
Myocardial infarction, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, or unstable angina within 1 year before study enrollment
History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on screening chest computed tomograph (CT) scan
Average systolic blood pressure of greater than 145 mm Hg or average diastolic blood pressure of greater than 85 mm Hg
Radiotherapy within 28 days of study enrollment or within 14 days of study enrollment for peripheral lesions
Prior AMG 706, panitumumab, or another anti-EGFr monoclonal antibody (mAb) (e.g., cetuximab [Erbitux®] or EMD 72000)
Systemic chemotherapy within 28 days before study enrollment
Major surgery within 28 days or minor surgery within 14 days of study enrollment
Central nervous system metastases (Exception: subjects with treated asymptomatic central nervous system metastases, those who have been clinically stable in the judgment of the investigator and off steroids for at least 30 days before the study enrollment are eligible)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: MD, Amgen

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Burris H, Stephenson J, Otterson GA, Stein M, McGreivy J, Sun YN, Ingram M, Ye Y, Schwartzberg LS. Safety and pharmacokinetics of motesanib in combination with panitumumab and gemcitabine-Cisplatin in patients with advanced cancer. J Oncol. 2011;2011:853931. doi: 10.1155/2011/853931. Epub 2011 Apr 14.

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