Phase 2 Study of NPC-1C Chimeric Monoclonal Antibody to Treat Pancreatic and Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Precision Biologics, Inc
Sponsor:
Information provided by (Responsible Party):
Precision Biologics, Inc
ClinicalTrials.gov Identifier:
NCT01040000
First received: December 23, 2009
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

The purpose of the phase 2 component of this study is to determine if giving the immune molecule NPC-1C to individuals who have cancer of the pancreas or gastrointestinal tract (colon or rectum) which has not responded to standard treatments can shrink or halt the growth of cancer, and to obtain additional data to study its effect on the immune system. Safety data will also be accumulated and evaluated during this study. NPC-1C is a monoclonal antibody that recognizes a specific tumor target on certain cancers. In laboratory studies, the antibody killed tumor cells in some colon and pancreatic cancers that express the NPC-1C antigen by a process called "antibody-dependent cell cytotoxicity" or ADCC.


Condition Intervention Phase
Metastatic Pancreatic Cancer
Metastatic Colorectal Cancer
Drug: NPC-1C/NEO-102
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Therapeutic, Open Label, Multi-Center Clinical Trial of NPC-1C, a Chimeric Monoclonal Antibody, in Adults With Recurrent, Locally Advanced Unresectable or Metastatic Pancreatic and Colorectal Cancer After Standard Therapy

Resource links provided by NLM:


Further study details as provided by Precision Biologics, Inc:

Primary Outcome Measures:
  • Efficacy will be assessed by analysis of CT scans pre and post therapy, clinical laboratory tests, and physical examinations. [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  • Efficacy OS [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    Using the recommended phase 2 dose (RP2D) evaluate the overall survival (OS) associated with administration of NPC-1C (NEO-102) in subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer or metastatic colorectal cancer that express NPC-1C target on tumor.


Secondary Outcome Measures:
  • Safety will be assessed by analysis of adverse experiences, clinical laboratory tests, and physical examinations. [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics and select immune responses to the antibody will be assessed. [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 116
Study Start Date: January 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NPC-1C/NEO-102 Drug: NPC-1C/NEO-102
Subjects will receive NPC-1C at a dose of 3.0 mg/kg. NPC-1C will be given intravenously (by vein) over approximately 1-6 hours, once every 2 weeks for 4 doses per course. Courses will be repeated in the absence of disease progression or unacceptable toxicity.
Other Name: Ensituximab

Detailed Description:

The limitations of many current therapeutic products for pancreatic cancer are widely recognized. Despite the development of several new treatment regimens for pancreatic cancer, little if any benefit has been appreciated, leaving this disease as one of the most significant unmet medical needs in cancer.

NPC-1C is a chimeric immunoglobulin molecule comprised from the variable region of the heavy chain and light chain of murine NPC-1, genetically engineered in-frame with the constant regions of a human IgG1 isotype. NPC-1, the predecessor of NPC-1C, was derived from a Tumor Associated Antigen (TAA) based vaccine that was previously tested in a Phase 1-2 clinical trial performed in the United States in the 1980's that explored the use of TAA therapy in patients with adenocarcinoma of the colon. These early studies demonstrated safety as well as preliminary evidence of activity in these patients treated with the vaccine.

NPC-1C antibody-staining studies demonstrate specific immunoreactivity with cancer tissues from colon and pancreas patients, whereas only weak binding, if at all, is observed in normal pancreas or colon tissues with no cross-reactivity observed in other normal human tissues. The Phase 2 portion of this trial is an open label, multi-center study estimated to treat approximately 30 patients with pancreatic cancer who have failed first line therapy, and 43 patients with metastatic colorectal cancer who are refractory to standard treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Age: >/= 18
  • Diagnosis:

    • Histologically confirmed recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas who have progressed after front line chemotherapy, OR
    • Histologically confirmed metastatic colorectal adenocarcinoma who have progressed after at least 2 standard chemotherapy regimens.
  • Tumor sections must stain >/= 20% positive for NPC-1C antibody/antigen target
  • Measurable disease (by RECIST)
  • Karnofsky performance status of >/= 50%
  • Laboratory Function (within 21 days of receiving first dose of study drug):

    • Hemoglobin > 8.5 g/dL, or on stable doses (hematocrit stable within 1 gram and dose stable for one month) of erythropoietin or similar medication.
    • Absolute neutrophil count (ANC) >/= 1,500/mm3
    • Platelets >/= 50,000/mm3
    • Total bilirubin </= 2.0 mg/dL
    • ALT and AST </= 2.5 times the ULN, or, if the patient has liver metastases, </= 5 times the ULN
    • Creatinine </= ULN
  • Voluntary written informed consent before performance of any study-related procedure that is not part of normal medical care.
  • Expected to be able to remain on a study protocol for at least 8 weeks.
  • Is post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control for the duration of the study. Male subject agrees to use an acceptable barrier method for contraception during the study.

EXCLUSION CRITERIA:

  • Has history of disseminated or uncontrolled brain metastases or central nervous system disease.
  • Ascites with abdominal distention.
  • Mechanical, non-reversible reason for not being able to eat, or have a likelihood of developing malignant bowel obstruction during the course of the induction phase of treatment; subjects with uncomplicated J-tubes will not be excluded.
  • Any major surgery within four weeks of enrollment.
  • Uncontrolled concomitant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  • Has another serious medical illness, including a second malignancy, or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • Pregnant or breast-feeding.
  • Any chemotherapeutic agents or corticosteroids within 2 weeks of study entry or biologic treatment within 4 weeks of study entry.
  • Use of any high risk medications that prolong the QT/QTc interval.
  • History of allergic reaction to Erbitux greater than grade 1.
  • Uncontrolled diabetes.
  • Prior history of a documented hemolytic event.
  • Receiving warfarin.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01040000

Locations
United States, Maryland
Johns Hopkins Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Sheila Linden, RN    410-614-4397    slinden2@jhmi.edu   
Contact: Nilofer Azad, M.D.    410-614-9169    nazad2@jhmi.edu   
Sub-Investigator: Luis A. Diaz, M.D.         
Sub-Investigator: Daniel Laheru, M.D.         
Sub-Investigator: Ross Donehower, M.D.         
Sub-Investigator: David Cosgrove, MBBCh         
Sub-Investigator: Dung Thi Le, M.D.         
Sub-Investigator: Keith McIntyre, CRNP         
Principal Investigator: Nilofer Azad, M.D.         
Sub-Investigator: Emily Petito, CRNP         
United States, New Jersey
Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Elizabeth Poplin, MD    732-235-7066    poplinea@cinj.rutgers.edu   
Contact: Samantha Williams, BS    732-235-9850    charlesm@cinj.rutgers   
Principal Investigator: Elizabeth Poplin, MD         
Sub-Investigator: Rebecca Moss, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Sherry Haley    919-668-1861    sherri.haley@duke.edu   
Principal Investigator: Michael A Morse, MD         
Sub-Investigator: Herbert Hurwitz, MD         
Sub-Investigator: Hope Uronis, MD         
Sub-Investigator: Syed Y Zafar, MD         
Sub-Investigator: Shiao-Wen D Hsu, MD, PhD         
Sub-Investigator: Gerard Blobe, MD, PhD         
Sub-Investigator: Evan Dropkin, PA-C         
Sub-Investigator: Leigh Howard, FNP         
Sub-Investigator: Margot O'Neill, PA-C         
Sub-Investigator: John Strickler, MD         
Sub-Investigator: Fatima Rangwala, M.D., Ph.D.         
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-9179
Contact: Muhammad S Beg, Medical Doctor       muhammad.beg@utsouthwestern.edu   
Contact: Tyson Dudley, MPH, MBA    214-648-7031    tyson.dudley@utsouthwestern.edu   
Sub-Investigator: Udit Verma, MD         
Sub-Investigator: Sirisha Karri, MD         
Sponsors and Collaborators
Precision Biologics, Inc
Investigators
Study Director: Philip M Arlen, M.D. Precision Biologics, Inc
  More Information

No publications provided

Responsible Party: Precision Biologics, Inc
ClinicalTrials.gov Identifier: NCT01040000     History of Changes
Other Study ID Numbers: Neogenix 0901
Study First Received: December 23, 2009
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Precision Biologics, Inc:
NPC-1C
Monoclonal antibody
Pancreatic Cancer
Adenocarcinoma of the pancreas
Ductal carcinoma of the pancreas
Duct cell carcinomas, pancreas
Carcinomas, pancreas duct cell
Pancreas duct cell carcinoma
Pancreatic duct cell carcinoma
Adenocarcinoma of the colon
Adenocarcinoma of the rectum
Colorectal cancer
Colorectal tumor
Colorectal neoplasm

Additional relevant MeSH terms:
Pancreatic Neoplasms
Colorectal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014