An Efficacy Study of MORAb-009 in Subjects With Pancreatic Cancer

A Phase 2 Randomized, Placebo-controlled, Double-blind Study of the Efficacy of MORAb-009 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer.

The purpose of this study is to investigate the activity of MORAb-009 when added to a standard regimen of gemcitabine in patients with previously untreated unresectable stage 3 or 4 pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: MORAb-009; Drug: Gemcitabine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Liege, Belgium, 4000
    • Services de gastro-entérologie et d'oncologie, CHC Saint-Joseph
  • Mechelen, Belgium, 2800
    • AZ Sint Maarten - digestive oncology unit - campus
  • Hainaut
    • Haine Saint Paul, Hainaut, Belgium, 7100
      • Centre Hospitalier Jolimont-Lobbes
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Queen Elizabeth II Health Sciences Center
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program London Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • Jewish General Hospital - Montreal
• Germany
  • Berlin, Germany, D 13353
    • Charité, Universitätsmedizin Berlin
  • Baden Wurttemburg
    • Freiburg, Baden Wurttemburg, Germany, D 79106
      • Klinik fuer Tumorbiologie an der Albert-Ludwigs-Universität Freiburg
    • Heidelberg, Baden Wurttemburg, Germany, D 69120
      • Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg, Universitätsklinikum Heidelberg
    • Heilbronn, Baden Wurttemburg, Germany, D 74078
      • SLK-Kliniken Heilbronn GmbH, Medizinische Klinik III
    • Ulm, Baden Wurttemburg, Germany, D 89081
      • Universitätsklinikum Ulm, Innere Medizin I
  • Bayern
    • München, Bayern, Germany, D 81675
      • II. Medizinische Klinik des Klinikums rechts der Isar
  • Nordrhein-Westfalen
    • Bielefeld, Nordrhein-Westfalen, Germany, D 33604
      • Stadtische Kliniken Bielefeld-Mitte, Klinik fur Hamatologie und Onkologie
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic I Provincial de Barcelona
  • Barcelona, Spain, 8025
    • Hospital De La Santa Creu I Sant Pau
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Madrid, Spain, 28040
    • Hospital Clinico Universitario San Carlos
  • Madrid, Spain, 28010
    • Hospital Madrid
• United States
  • California
    • La Jolla, California, United States, 92037-0845
      • Moores UCSD Cancer Center
    • San Diego, California, United States, 92108
      • Southern California Permanente Medical Group
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
    • Vallejo, California, United States, 94589
      • Kaiser Permanente
  • Connecticut
    • Southington, Connecticut, United States, 06489
      • Cancer Center of Central Connecticut
    • Torrington, Connecticut, United States, 06790
      • Connecticut Oncology & Hematology
  • Florida
    • Boynton Beach, Florida, United States, 33435
      • Palm Beach Institute of Hematology and Oncology
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Lake Worth, Florida, United States, 33461
      • Hematology Oncology Associates of the Palm Beaches
  • Illinois
    • Skokie, Illinois, United States, 60076
      • Hematology-Oncology Associates of Illinois, LLC
    • Urbana, Illinois, United States, 61801
      • Carle Clinic Assoc.
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Jayne Gurtler, MD, Laura Brinz, MD, & Angelo Russo, MD
  • Michigan
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Center, Oncology, Clinical Trials
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08003
      • The Center for Cancer and Hematologic Disease
  • New York
    • Lake Success, New York, United States, 11042
      • Arena Oncology Associates, P.C.
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Hanover Medical Specialists, MD
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • South Carolina
    • Columbia, South Carolina, United States, 10595
      • South Carolina Oncology Associates, PA
  • Texas
    • Arlington, Texas, United States, 76012
      • Arlington Cancer Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • South Texas Onocology Hemotology, PA
  • Washington
    • Lacey, Washington, United States, 98503
      • Providence Western Washington Oncology
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Clinical Cancer 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. Female or male subjects, ≥ 18 years of age, with cytologically or histologically confirmed diagnosis of pancreatic adenocarcinoma.
2. Must have measurable disease, as defined by RECIST or evaluable by clinical signs/symptoms (e.g. ascites, pleural effusion, or lesions of less than 2 cm) supported by biomarker, radiologic, or pathologic studies conducted within 4 weeks prior to study entry.
3. Must have unresectable disease and have received no prior chemotherapy or radiation therapy for their pancreatic cancer.
4. Karnofsky performance status of greater than or equal to 70 %.
5. Female subjects of childbearing potential and all male subjects must be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period.
6. Other significant medical conditions must be well-controlled and stable in the opinion of the investigator for at least 30 days prior to Study Day 1.

7. Laboratory and clinical results within the 2 weeks prior to Study Day 1 as follows:

   Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL Serum bilirubin ≤ 2.0 mg/dL Aspartate transaminase (AST)* ≤ 5 x upper limit of normal (ULN) Alanine transaminase (ALT)* ≤ 5 x ULN Alkaline phosphatase* ≤ 5 x ULN Serum creatinine ≤ 2.0 mg/dL Stenting to reduce liver functions to qualifying levels is permitted.

   * Subjects with liver function abnormalities greater than the ULN are eligible only if in the opinion of the investigator they are due to disease obstruction of the bile ducts or metastatic disease.

8. Must be willing and able to provide written informed consent.

Exclusion Criteria:

1. Known central nervous system (CNS) tumor involvement.
2. Evidence of other active malignancy requiring treatment.
3. Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class 3 or 4 angina not well controlled by medication, or myocardial infarction within 6 months).
4. Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Note: Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia [SVT], are eligible).
5. Active serious systemic disease, including active bacterial or fungal infection.
6. Active viral hepatitis or symptomatic human immunodeficiency virus (HIV) infection.
7. Prior chemotherapy or radiation therapy for their pancreatic cancer.
8. Breast-feeding, pregnant, or likely to become pregnant during the study.
9. No other concurrent immunotherapy (e.g., immunosuppressants or chronic use of systemic corticosteroids with the exception that low-dose corticosteroids are allowed)
10. Known hypersensitivity to a monoclonal antibody or biologic therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MORAb-009; MORAb-009 plus gemcitabine ('MORAb-009'): MORAb-009 was administered at 5 mg/kg on Day 1 of Weeks 1 through 7 during the first cycle and on Day 1 of Weeks 1 through 3 of subsequent cycles. Gemcitabine was administered by i.v. infusion at an initial dose of 1000 mg/m2 once weekly for up to 7 weeks (or until toxicity necessitated reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles consisted of infusions once weekly for 3 consecutive weeks, followed by a week of rest from treatment.	Drug: MORAb-009; Monoclonal antibody administered once weekly by intravenous injection.; Drug: Gemcitabine; Gemcitabine was administered by i.v. infusion at an initial dose of 1000 mg/m2 once weekly for up to 7 weeks (or until toxicity necessitated reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles consisted of infusions once weekly for 3 consecutive weeks, followed by a week of rest from treatment.
Active Comparator: Placebo; Placebo plus gemcitabine ('Placebo') Placebo was administered on Day 1 of Weeks 1 through 7 during the first cycle and on Day 1 of Weeks 1 through 3 of subsequent cycles. Gemcitabine was administered by i.v. infusion at an initial dose of 1000 mg/m2 once weekly for up to 7 weeks (or until toxicity necessitated reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles consisted of infusions once weekly for 3 consecutive weeks, followed by a week of rest from treatment.	Drug: Gemcitabine; Gemcitabine was administered by i.v. infusion at an initial dose of 1000 mg/m2 once weekly for up to 7 weeks (or until toxicity necessitated reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles consisted of infusions once weekly for 3 consecutive weeks, followed by a week of rest from treatment.; Drug: Placebo; As per package insert.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	This measure was defined as the time (in months) from the date of randomization to the date of death, whatever the cause. The primary endpoint was analyzed when 110 events (deaths) were observed. In the absence of death confirmation or for subjects alive at the time of analysis, the survival time will be censored at the date of the last study follow-up.	1-21 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free Survival (PFS) is defined as the time from the date of randomization to the date of the first observation of disease progression (clinical or radiological) or death due to any cause. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline. If progression or death is not observed, the PFS time will be censored at the date of the last tumor assessment without evidence of progression prior to the date of initiation of further anticancer treatment.	1-21 Months
Best Overall Response Rate	Best overall response is the number of participants with a Complete Response (CR) or Partial Response (PR), as classified by independent blinded review of the CT or MRI images, based on RECIST 1.0. A CR is the disappearance of all target lesions. PR is at least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum longest diameter. Progressive Disease (PD) is at least a 20% increase in the sum of the longest diameters of target lesions or the appearance of one or more new lesions. Stable disease (SD) is neither CR, PR or PD.	Baseline to response up to 21 months

Collaborators and Investigators

• Sponsor: Morphotek

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: December 7, 2007
• First Submitted That Met QC Criteria: December 7, 2007
• First Posted (Estimate): December 11, 2007

Study Record Updates

• Last Update Posted (Estimate): September 9, 2015
• Last Update Submitted That Met QC Criteria: September 4, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• 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: MORAb-009-002