A Phase 1 Study of Safety and Bioactivity With FG-3019 in Combination With Gemcitabine and Erlotinib for Subjects With Locally Advanced or Metastatic Pancreatic Cancer

Objectives

• Primary: To evaluate the safety and tolerability of FG-3019 in combination with gemcitabine and erlotinib
• Secondary: To evaluate the efficacy and pharmacokinetics of FG-3019 in combination with gemcitabine and erlotinib

Study Overview

• Status: Completed
• Conditions: Locally Advanced or Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: FG-3019

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305-5152
      • Stanford University School of Medicine
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland, Case Comprehensive Cancer Center
  • Oregon
    • Portland, Oregon, United States
      • Oregon Health Sciences University (OHSU)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • University of Pittsburgh
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Written informed consent
2. Males and females aged ≥18 years old
3. Histologically or cytologically confirmed adenocarcinoma of the pancreas
4. Locally advanced (Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas
5. Spiral CT scan demonstrating at least one pancreatic adenocarcinoma measurable lesion according to RECIST criteria and PET scan showing metabolically active lesion (for the last six subjects in the 15 mg/kg and the subjects in the 25 mg/kg FG-3019 dose cohorts only)
6. Women of childbearing potential and men must use effective contraception during and for at least 90 days following study participation. Women of childbearing potential must have a negative Screening serum pregnancy test.
7. ECOG performance status score of 0-1
8. Life expectancy >12 weeks
9. Ability to adhere to the study visit schedule and understand and comply with all protocol requirements and instructions from study staff

Exclusion Criteria

1. Absolute neutrophil count (ANC) <500 cells/mm3
2. Hemoglobin <10.0 g/dL
3. Platelet count <100,000 cells/mm3
4. Bilirubin >2.0 x upper limit of normal (ULN)
5. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2.5 x ULN, or >3.5 x ULN if liver metastases are present
6. If the subject is diabetic, HbA1c >10%
7. Current pregnancy or breast feeding due to recent pregnancy
8. History of another malignancy in the past 2 years with the exception of basal cell or squamous cell carcinoma of the skin
9. Previous chemotherapy with gemcitabine
10. Previous systemic antineoplastic agent (other than adjuvant 5-fluorouracil as radio-sensitizer)
11. Adjuvant 5-fluorouracil within 28 days prior to Day 1
12. Major surgery within 28 days prior to Day 1 (stent placement is allowed)
13. Radiation therapy within 28 days prior to Day 1
14. Clinical evidence or any history of brain metastasis
15. Uncontrolled hypertension (systolic blood pressure [SBP] >180 mmHg or diastolic blood pressure [DBP] >105 mmHg)
16. New York Heart Association Class III or IV congestive heart failure
17. History of allergic or anaphylactic reaction to human, humanized, or chimeric monoclonal antibodies
18. Current clinical or laboratory evidence of active infection requiring antibiotic or antiviral therapy
19. Active major gastrointestinal bleeding
20. Full-dose heparin therapy within 28 days prior to Day 1
21. Participation in studies of investigational products within 42 days prior to Day 1
22. Clinically significant and uncontrolled medical condition considered a high risk for participation in an investigational study or a likelihood that the subject will be unable to comply with protocol requirements and complete the trial (e.g., emphysema requiring supplemental oxygen, poorly controlled arrhythmia, psychiatric illness, Alzheimer's disease)
23. Current abuse of alcohol or drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FG-3019; All subjects are treated with FG-3019	Drug: FG-3019; 3mg/kg IV, 10mg/kg IV, 15mg/kg IV, 25mg/kg, 35mg/kg IV, 45mg/kg IV - Biweekly, 35/17.5mg/kg, 45/22.5 mg/kg - Weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety and tolerability of FG-3019 in combination with gemcitabine and erlotinib	Through the end of the study

Secondary Outcome Measures

Outcome Measure	Time Frame
FG-3019 PK parameters	Through the end of the study
Time to Progression (TTP)	Through the end of the study
6-month, 12-month and overall median survival rates	Through the end of the study
Maximal tumor response as determined by RECIST criteria	Through the end of the study

Collaborators and Investigators

• Sponsor: FibroGen
• Investigators: Principal Investigator: Albert C Koong, MD, PhD, Stanford University; Principal Investigator: J. Marc Pipas, MD, Dartmouth-Hitchcock Medical Center; Principal Investigator: Vincent J Picozzi, MD, PhD, Virginia Mason Hospital/Medical Center; Principal Investigator: Peter J O'Dwyer, MD, University of Pennsylvania; Principal Investigator: Smitha Krishnamurthi, MD, University Hospitals of Cleveland, Case Comprehensive Cancer Center; Principal Investigator: Charles Lopez, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: May 4, 2009
• First Submitted That Met QC Criteria: August 12, 2010
• First Posted (ESTIMATE): August 13, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): August 6, 2014
• Last Update Submitted That Met QC Criteria: August 4, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Pancreatic Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: FGCL-MC3019-028