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

Phase 1

Terminated

• Conditions: Lung Cancer; Pancreatic Cancer; Esophageal Cancer
• Interventions: Biological: Panitumumab; Drug: AMG 706; Drug: Gemcitabine; Drug: Cisplatin

• Registration Number: NCT00101907
• Lead Sponsor: Amgen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2004-12
• Study First Submitted: 2005-01-18
• Study First Submitted QC: 2005-01-18
• Study First Posted: 2005-01-19
• Primary Completion: 2007-06
• Study Completion: 2008-04
• Results First Submitted: 2010-08-13
• Status Verified: 2014-02
• Results First Submitted QC: 2014-02-03
• Last Update Submitted: 2014-02-03
• Results First Posted: 2014-03-20
• Last Update Posted: 2014-03-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Panitumumab + Gem/Cis	Panitumumab	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.
50 mg QD AMG 706 + panitumumab + Gem/Cis	AMG 706	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.
50 mg QD AMG 706 + panitumumab + Gem/Cis	Panitumumab	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.
75 mg QD AMG 706 + panitumumab + Gem/Cis	AMG 706	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.
75 mg QD AMG 706 + panitumumab + Gem/Cis	Panitumumab	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.
100 mg QD AMG 706 + panitumumab + Gem/Cis	Panitumumab	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.
125 mg QD AMG 706 + panitumumab + Gem/Cis	Panitumumab	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.
75 mg BID AMG 706 + panitumumab + Gem/Cis	AMG 706	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.
75 mg BID AMG 706 + panitumumab + Gem/Cis	Panitumumab	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.
100 mg QD AMG 706 + panitumumab + Gem/Cis	AMG 706	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.
125 mg QD AMG 706 + panitumumab + Gem/Cis	AMG 706	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.
Panitumumab + Gem/Cis	Gemcitabine	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.
Panitumumab + Gem/Cis	Cisplatin	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.
50 mg QD AMG 706 + panitumumab + Gem/Cis	Gemcitabine	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.
50 mg QD AMG 706 + panitumumab + Gem/Cis	Cisplatin	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.
75 mg QD AMG 706 + panitumumab + Gem/Cis	Gemcitabine	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.
75 mg QD AMG 706 + panitumumab + Gem/Cis	Cisplatin	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.
100 mg QD AMG 706 + panitumumab + Gem/Cis	Gemcitabine	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.
100 mg QD AMG 706 + panitumumab + Gem/Cis	Cisplatin	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.
125 mg QD AMG 706 + panitumumab + Gem/Cis	Gemcitabine	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.
125 mg QD AMG 706 + panitumumab + Gem/Cis	Cisplatin	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.
75 mg BID AMG 706 + panitumumab + Gem/Cis	Gemcitabine	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.
75 mg BID AMG 706 + panitumumab + Gem/Cis	Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Participant Incidence of Adverse Events	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.	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With an Objective Tumor Response	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.	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.
Tmax	Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.	Time after dosing when maximum plasma concentration was observed for AMG 706
Cmax	Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.	The maximum observed plasma concentration after AMG 706 dosing
AUC0-24	Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.	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.
AUC0-inf	Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.	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.