A Randomized Study of Amplimexon (Imexon) With Gemcitabine in Pancreatic Cancer

A Phase 2 Randomized, Double-Blind, Multicenter Trial of Amplimexon® Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy Naïve Pancreatic Adenocarcinoma (Stage IV)

The purpose of this study is to determine if imexon in combination with gemcitabine could improve overall survival as compared to gemcitabine alone in subjects with pancreatic cancer that has spread to other organs such as the liver or lungs. The study will also look at the safety of the combination as compared to gemcitabine alone. Participants in the study will be randomly assigned to either treatment and neither the participant or their doctors will know which treatment they will be receiving.

Study Overview

• Status: Completed
• Conditions: Pancreatic Neoplasms
• Intervention / Treatment: Drug: imexon in combination with gemcitabine; Drug: imexon placebo + gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Birmingham Hematology and Oncology- US Oncology
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Arizona Clinical Research Center
    • Tucson, Arizona, United States, 85704
      • AZ Onc Associates D.B.A. Hematology Oncology- US Oncology
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Center- US Oncology
  • Florida
    • Ocala, Florida, United States, 34471
      • Ocala Oncology Center- US Oncology
    • Orlando, Florida, United States, 34761
      • Cancer Centers of Florida- US Oncology
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Peachtree Hematology and Oncology Consultants
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Hematology Oncology Associates of Illinois- US Oncology
    • Niles, Illinois, United States, 60714
      • Cancer Care & Hematolog Specialists of Chicagoland- US Oncology
  • Indiana
    • Indianapolis, Indiana, United States, 46227
      • Central Indiana Cancer Centers- US Oncology
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
    • Terre Haute, Indiana, United States, 47802
      • Hope Center- US Oncology
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • University of Kentucky, Hematology/Oncology/BMT Clinical Research
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Cancer Center, LLC- US Oncology
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada- US Oncology
  • New Jersey
    • Flemington, New Jersey, United States, 08822
      • Hunterdon Regional Cancer Center
    • Mount Holly, New Jersey, United States, 08060
      • Hematology Oncology Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Hematology Oncology Associates
    • Las Cruces, New Mexico, United States, 88011
      • University of New Mexico Cancer Center South
    • Santa Fe, New Mexico, United States, 87505
      • New Mexico Cancer Care Associates- US Oncology
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Cancer Center of North Carolina- US Oncology
  • Pennsylvania
    • Kingston, Pennsylvania, United States, 18704
      • Medical Onc Assoc of Wyoming Valley, PC- US Oncology
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute
    • Pottstown, Pennsylvania, United States, 19464
      • Pottstown Memorial Medical Center
    • Upland, Pennsylvania, United States, 19013
      • Associates in Hematology-Oncology P.C. US Oncology
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital Regional Medical Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Clinic
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Oncology - Amarillo- US Oncology
    • Beaumont, Texas, United States, 77702
      • Mamie Mcfaddin Ward Cancer Center, Texas Oncology- US Oncology
    • Bedford, Texas, United States, 76022
      • Texas Oncology P.A.- Bedford- US Oncology
    • Dallas, Texas, United States, 75230
      • Texas Cancer Center at Medical City- US Oncology
    • Dallas, Texas, United States, 75231
      • Texas Oncology P.A. - Dallas- US Oncology
    • Dallas, Texas, United States, 75237
      • Methodist Charlton Cancer Center - Texas Oncology- US Oncology
    • Odessa, Texas, United States, 79761
      • Texas Oncology - Odessa- US Oncology
    • Temple, Texas, United States, 76508
      • Scott and White Hospital and Clinics
    • Waco, Texas, United States, 76712
      • Texas Oncology Cancer Care and Research Center- US Oncology
    • Wichita Falls, Texas, United States, 76310
      • Texoma Cancer Center- US Oncology
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates- US Oncology
    • Salem, Virginia, United States, 24153
      • Onc & Hematology Assoc. of Southern VA, Inc D.B.A. - US Oncology
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest- US Oncology
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists- US Oncology

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. Patients with histologically or cytologically confirmed, chemotherapy naive, metastatic pancreatic adenocarcinoma (Stage IV). This does not include patients with only locally advanced pancreatic cancer.
2. At least one unidimensional measurable metastatic lesion by contrast enhanced CT scan (or MRI in patients ineligible for contrast enhanced CT) that are outside any prior radiation port.
3. Age at least 18 years.
4. ECOG performance status 0 or 1.
5. No prior chemotherapy or radiation therapy.
6. Projected life expectancy at least 2 months.
7. If female, neither pregnant nor lactating.
8. If of child bearing potential must agree to, and be able to use adequate contraception.
9. Concomitant disease: No respiratory insufficiency requiring oxygen therapy; no angina at rest; no myocardial infarction in previous 3 months; no life threatening ventricular arrhythmias. No uncompensated CHF or NY Heart Association class 3 or 4 cardiac disease.
10. No other concurrent active malignancy.
11. No infection requiring parenteral antibiotic therapy at the start of protocol treatment.

12. Laboratory values within the following criteria:

    Hgb greater than or equal to 9 gm/dL WBC greater than or equal 3,500/mm^3 ANC greater than or equal 1,500/mm^3 Platelet count greater than or equal 100,000/mm^3 Creatinine greater than or equal 2.0 Bilirubin less than or equal to 2.0 Hepatic enzymes (AST, ALT) less than or equal 3 times upper limit of normal (ULN)

13. G6PD level greater than or equal lower limit of normal (LLN).
14. Able to render informed consent and follow protocol requirements.

Exclusion Criteria:

1. Patients with locally advanced, non-metastatic pancreas cancer (Stage III or below).
2. Age less than 18 years.
3. ECOG performance status 2 or greater.
4. Prior anticancer drug therapy for metastatic disease.
5. Ascites.
6. Prior abdominal or thoracic surgery < 4 weeks before the start of therapy.
7. Current or prior brain metastases. Brain MRI or CT required pre-registration only if the patient has CNS symptoms indicating a need for evaluation.
8. Life expectancy projected less than 2 months.
9. Pregnancy or lactation.
10. Unable or unwilling to utilize medically acceptable contraception if of childbearing potential.
11. Laboratory parameters outside of specified ranges, (see above).
12. Infection requiring parenteral antibiotics.
13. NY Heart Association stage 3 or 4 heart disease.
14. Unable to render informed consent.
15. Failure to meet any of the eligibility criteria as outlined above.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: imexon + gemcitabine	Drug: imexon in combination with gemcitabine; 875 mg/m^2 imexon IV + 1000 mg/m^2 gemcitabine IV; Other Names: Amplimexon, Gemzar
Active Comparator: Placebo + gemcitabine; Placebo in combination with gemcitabine	Drug: imexon placebo + gemcitabine; imexon placebo IV + 1000 mg/m^2 gemcitabine IV; Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival for the Intent to Treat Population	To compare the overall survival duration of the two treatment arms. Overall survival is measured from the time of randomization until reported death. Subjects were censored at last time known alive if lost to follow-up. Alive patients were censored at the last survival follow-up. Follow-up was monthly after off study treatment.	up to 2 years
To Evaluate and Compare the Tolerability and Toxicity of the Two Treatment Arms by Comparing Adverse Events	Number of Participants with Adverse Events were compared between the two arms to detect any differences in number or types of events	Adverse events were collected from the time of treatment until the participant went off study treatment, an average of 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rates of the Two Treatment Arms	Objective response is measured by tumor reduction as defined in the RECIST criteria. Tumor shrinkage must be at least 30% to qualify as an objective response.	one year
Progression Free Survival	To compare the median progression free survival (PFS) of the two treatment arms. Progression free survival is measured from randomization until the subject has documented disease progression by an objective measure. Subjects were censored if no documented progression had occurred at the one year time point. Subjects must be alive with no more than 20% increase in tumor size to qualify for progression free survival. Changes in tumor size are defined by RECIST criteria.	one year

Collaborators and Investigators

• Sponsor: AmpliMed Corporation
• Investigators: Study Director: Evan Hersh, MD, AmpliMed Corporation

Publications and helpful links

General Publications

• Cohen SJ, Zalupski MM, Conkling P, Nugent F, Ma WW, Modiano M, Pascual R, Lee FC, Wong L, Hersh E. A Phase 2 Randomized, Double-Blind, Multicenter Trial of Imexon Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy-naive Pancreatic Adenocarcinoma. Am J Clin Oncol. 2018 Mar;41(3):230-235. doi: 10.1097/COC.0000000000000260.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2008
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: March 10, 2008
• First Submitted That Met QC Criteria: March 10, 2008
• First Posted (Estimate): March 17, 2008

Study Record Updates

• Last Update Posted (Actual): March 20, 2019
• Last Update Submitted That Met QC Criteria: March 11, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: pancreatic cancer; metastatic; chemotherapy naive
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: AMP-019