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

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label, Dose-Finding Study to Evaluate the Safety of AMG 706 Plus Panitumumab Plus Gemcitabine-Cisplatin in the Treatment of Subjects With Advanced Cancer

Conditions
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Lung Cancer, Pancreatic Cancer, Esophageal Cancer

Intervention / Treatment
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* Drug: AMG 706
* Biological: Panitumumab
* Drug: Gemcitabine
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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For complete inclusion and exclusion, please refer to the investigator. 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panitumumab + Gem/Cis<br>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. | Biological: Panitumumab<br>* Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.<br>* Other names: Vectibix;Drug: Gemcitabine<br>* Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.<br>* Other names: cis-diamminedichloridoplatinum(II) (CDDP);|
| Experimental: 50 mg QD AMG 706 + panitumumab + Gem/Cis<br>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<br>* 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.<br>Biological: Panitumumab<br>* Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.<br>* Other names: Vectibix;Drug: Gemcitabine<br>* Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.<br>* Other names: cis-diamminedichloridoplatinum(II) (CDDP);|
| Experimental: 75 mg QD AMG 706 + panitumumab + Gem/Cis<br>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<br>* 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.<br>Biological: Panitumumab<br>* Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.<br>* Other names: Vectibix;Drug: Gemcitabine<br>* Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.<br>* Other names: cis-diamminedichloridoplatinum(II) (CDDP);|
| Experimental: 100 mg QD AMG 706 + panitumumab + Gem/Cis<br>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<br>* 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.<br>Biological: Panitumumab<br>* Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.<br>* Other names: Vectibix;Drug: Gemcitabine<br>* Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.<br>* Other names: cis-diamminedichloridoplatinum(II) (CDDP);|
| Experimental: 125 mg QD AMG 706 + panitumumab + Gem/Cis<br>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<br>* 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.<br>Biological: Panitumumab<br>* Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.<br>* Other names: Vectibix;Drug: Gemcitabine<br>* Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.<br>* Other names: cis-diamminedichloridoplatinum(II) (CDDP);|
| Experimental: 75 mg BID AMG 706 + panitumumab + Gem/Cis<br>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<br>* 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.<br>Biological: Panitumumab<br>* Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.<br>* Other names: Vectibix;Drug: Gemcitabine<br>* Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.<br>* Other names: cis-diamminedichloridoplatinum(II) (CDDP);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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

| Outcome Measure | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Cancer, AMG 706, Panitumumab, Gemcitabine-Cisplatin