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

February 3, 2014 updated by: Amgen

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Phase 1

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

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

How is the study designed?

Design Details

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

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.
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.
Other Names:
  • Vectibix
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.
Other Names:
  • Gemzar
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
  • cisplatinum
  • cis-diamminedichloridoplatinum(II) (CDDP)
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.
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.
Other Names:
  • Vectibix
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.
Other Names:
  • Gemzar
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
  • cisplatinum
  • cis-diamminedichloridoplatinum(II) (CDDP)
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.
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.
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.
Other Names:
  • Vectibix
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.
Other Names:
  • Gemzar
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
  • cisplatinum
  • cis-diamminedichloridoplatinum(II) (CDDP)
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.
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.
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.
Other Names:
  • Vectibix
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.
Other Names:
  • Gemzar
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
  • cisplatinum
  • cis-diamminedichloridoplatinum(II) (CDDP)
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.
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.
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.
Other Names:
  • Vectibix
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.
Other Names:
  • Gemzar
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
  • cisplatinum
  • cis-diamminedichloridoplatinum(II) (CDDP)
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.
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.
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.
Other Names:
  • Vectibix
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.
Other Names:
  • Gemzar
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
  • cisplatinum
  • cis-diamminedichloridoplatinum(II) (CDDP)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participant Incidence of Adverse Events
Time Frame: 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.
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
Time Frame: 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.
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 Frame: 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
Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.
Cmax
Time Frame: 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
Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.
AUC0-24
Time Frame: 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.
Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.
AUC0-inf
Time Frame: 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.
Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.

Collaborators and Investigators

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

Sponsor

Amgen

Publications and helpful links

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

General Publications

Helpful Links

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 Major Dates

Study Start

December 1, 2004

Primary Completion (Actual)

June 1, 2007

Study Completion (Actual)

April 1, 2008

Study Registration Dates

First Submitted

January 18, 2005

First Submitted That Met QC Criteria

January 18, 2005

First Posted (Estimate)

January 19, 2005

Study Record Updates

Last Update Posted (Estimate)

March 20, 2014

Last Update Submitted That Met QC Criteria

February 3, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20040206

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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