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Safety and Efficacy Study of Different Doses of 90Y-hPAM4 Combined With Gemcitabine in Pancreatic Cancer
This study is currently recruiting participants.
Verified by Immunomedics, Inc., January 2009
Sponsored by: Immunomedics, Inc.
Information provided by: Immunomedics, Inc.
ClinicalTrials.gov Identifier: NCT00603863
  Purpose

This is a study to test whether different doses of 90Y-hPAM4 are safe to give in combination with gemcitabine in patients with previously untreated pancreatic cancer.


Condition Intervention Phase
Pancreatic Cancer
Biological: IMMU-107 (hPAM4)
Phase I
Phase II

MedlinePlus related topics: Cancer Pancreatic Cancer
Drug Information available for: Gemcitabine hydrochloride Gemcitabine Immunoglobulins Globulin, Immune Pancrelipase Ultrase
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase Ib Study of Fractionated 90Y-hPAM4 Plus Gemcitabine in Patients With Previously Untreated Advanced Pancreatic Cancer.

Further study details as provided by Immunomedics, Inc.:

Primary Outcome Measures:
  • safety will be evaluated based upon physical examinations, hematology and chemistry laboratory testing as well as toxicity [ Time Frame: over 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • efficacy [ Time Frame: over 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2008
Arms Assigned Interventions
multiple dose levels: Experimental
1 of 3 different dose levels of 90Y-hPAM4 given once weekly for 3 weeks along with 4 weekly doses of gemcitabine.
Biological: IMMU-107 (hPAM4)
90Y-hPAM4 once weekly for 3 weeks gemcitabine once weekly for 4 weeks

Detailed Description:

After confirming eligibility and undergoing baseline assessments, all patients receive 111In-hPAM4 administered at least one week prior to scheduled therapy, with scintigraphic images and blood samples obtained at intervals over 7 days for analysis of tumor targeting, biodistribution, dosimetry, and pharmacokinetics. The Investigator must confirm there is acceptable biodistribution for therapeutic treatment and the radiation dose estimates for the planned cohort 90Y doses must not exceed defined organ radiation dosimetry limits (i.e., 3,000 cGy for liver, 2,000 cGy for the lungs and kidneys, 300 cGy for red bone marrow). Otherwise the patient is not eligible for radioimmunotherapy with 90Y-hPAM4. Patients receive a 4-week treatment cycle with once-weekly 30-minute gemcitabine infusions beginning one week prior to the first 90Y-hPAM4dose and continuing during the 3 consecutive weeks over which onceweekly 90Y-hPAM4 doses are given. Depending on toxicity, patient cohorts will receive one of several possible 90Y and gemcitabine dose combinations. Post-treatment evaluations conducted until instituting retreatment or for a maximum period of 12 weeks.

  Eligibility

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

Inclusion Criteria:

  • Male or female patients, >18 years of age, who are able to understand and give written informed consent.
  • Histologically or cytologically confirmed pancreatic adenocarcinoma.
  • Stage III (locally advanced, unresectable) or Stage IV (metastatic) disease, including patients who underwent surgery but had incomplete resections.
  • Treatment naïve (no prior chemotherapy, radiotherapy or investigational agents for pancreatic cancer)
  • Karnofsky performance status > 70 % (Appendix A).
  • Expected survival > 3 months.
  • At least 4 weeks beyond major surgery and recovered from all acute toxicities
  • At least 2 weeks beyond corticosteroids, except low doses (i.e., 20 mg/day of prednisone or equivalent) to treat nausea or other illness such as rheumatoid arthritis
  • Adequate hematology without ongoing transfusional support (hemoglobin > 12 g/dL, ANC > 2,000 per mm3, platelets > 150,000 per mm3)
  • Adequate renal and hepatic function (creatinine and bilirubin ≤ 1.5 X IULN, AST and ALT ≤ 2.0 X IULN)
  • Otherwise, all toxicity at study entry <Grade 1 by NCI CTC v3.0.

Exclusion Criteria:

  • Women who are pregnant or lactating.

    • Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period.
    • Known metastatic disease to the central nervous system.
    • Presence of bulky disease (defined as any single mass >10 cm in its greatest dimension)
    • Patients with >Grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
    • Prior radiation dose >3,000 cGy to the liver, >2,000 cGy to lungs and kidneys or prior external beam irradiation to a field that includes more than 30% of the red marrow.
    • Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are not excluded, but patients with other prior malignancies must have had at least a 5-year disease free interval.
    • Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.
    • Known history of active coronary artery disease, unstable angina, myocardial infarction, or congestive heart failure present within 6 months or cardiac arrhythmia requiring anti-arrhythmia therapy.
    • Known history of active COPD, or other moderate-to-severe respiratory illness present within 6 months.
    • Known autoimmune disease or presence of autoimmune phenomena (except rheumatoid arthritis requiring only low dose maintenance corticosteroids).
    • Infection requiring intravenous antibiotic use within 1 week.
    • Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00603863

Contacts
Contact: Heather Horne 973-727-7589 hhorne@immunomedics.com

Locations
United States, California
Hoag Cancer Center Not yet recruiting
Newport Beach, California, United States, 92658
United States, Delaware
Christiana Care Health Services Recruiting
Newark, Delaware, United States, 19718
United States, Florida
Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Moffit Cancer Center Not yet recruiting
Tampa, Florida, United States, 33612
Contact: Susan Garl     973-727-7195     sgarl@immunomedics.com    
United States, Indiana
Goshen Cancer Center Recruiting
Goshen, Indiana, United States, 46526
Contact: Rebecca Eickhoff, RN     574-535-2974     reickhoff@goshenhealth.com    
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
New York Presbyterian Hospital/Weill Cornell Medical Center Not yet recruiting
New York, New York, United States, 10021
Mt. Sinai Medical Center Not yet recruiting
New York, New York, United States, 10029
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Susan Garl     973-727-7195     sgarl@immunomedics.com    
Contact: Heather Horne            
United States, Ohio
Ohio State University Medical Center Not yet recruiting
Columbus, Ohio, United States, 43210
United States, Wisconsin
Aspirus REgional Cancer Center Not yet recruiting
Wausau, Wisconsin, United States, 54401
Sponsors and Collaborators
Immunomedics, Inc.
Investigators
Study Chair: William Wegener, MD, PHD Immunomedics, Inc.
  More Information

Publications:
Gold DV, Karanjawala Z, Modrak DE, Goldenberg DM, Hruban RH. PAM4-Reactive MUC1 Is a Biomarker for Early Pancreatic Adenocarcinoma. Clin Cancer Res. 2007 Dec 15;13(24):7380-7.
Modrak DE, Gold DV, Goldenberg DM. Sphingolipid targets in cancer therapy. Mol Cancer Ther. 2006 Feb;5(2):200-8. Review.
Gold DV, Modrak DE, Ying Z, Cardillo TM, Sharkey RM, Goldenberg DM. New MUC1 serum immunoassay differentiates pancreatic cancer from pancreatitis. J Clin Oncol. 2006 Jan 10;24(2):252-8. Epub 2005 Dec 12.
Modrak DE, Cardillo TM, Newsome GA, Goldenberg DM, Gold DV. Synergistic interaction between sphingomyelin and gemcitabine potentiates ceramide-mediated apoptosis in pancreatic cancer. Cancer Res. 2004 Nov 15;64(22):8405-10.
Gold DV, Modrak DE, Schutsky K, Cardillo TM. Combined 90Yttrium-DOTA-labeled PAM4 antibody radioimmunotherapy and gemcitabine radiosensitization for the treatment of a human pancreatic cancer xenograft. Int J Cancer. 2004 Apr 20;109(4):618-26.
Gold DV, Schutsky K, Modrak D, Cardillo TM. Low-dose radioimmunotherapy ((90)Y-PAM4) combined with gemcitabine for the treatment of experimental pancreatic cancer. Clin Cancer Res. 2003 Sep 1;9(10 Pt 2):3929S-37S.
Modrak DE, Gold DV, Goldenberg DM, Blumenthal RD. Colonic tumor CEA, CSAp and MUC-1 expression following radioimmunotherapy or chemotherapy. Tumour Biol. 2003 Jan-Feb;24(1):32-9.
Reddy PK, Gold DV, Cardillo TM, Goldenberg DM, Li H, Burton JD. Interferon-gamma upregulates MUC1 expression in haematopoietic and epithelial cancer cell lines, an effect associated with MUC1 mRNA induction. Eur J Cancer. 2003 Feb;39(3):397-404.
Cardillo TM, Blumenthal R, Ying Z, Gold DV. Combined gemcitabine and radioimmunotherapy for the treatment of pancreatic cancer. Int J Cancer. 2002 Jan 20;97(3):386-92.
Cardillo TM, Ying Z, Gold DV. Therapeutic advantage of (90)yttrium- versus (131)iodine-labeled PAM4 antibody in experimental pancreatic cancer. Clin Cancer Res. 2001 Oct;7(10):3186-92.
Gold DV, Cardillo T, Vardi Y, Blumenthal R. Radioimmunotherapy of experimental pancreatic cancer with 131I-labeled monoclonal antibody PAM4. Int J Cancer. 1997 May 16;71(4):660-7.
Mariani G, Molea N, Bacciardi D, Boggi U, Fornaciari G, Campani D, Salvadori PA, Giulianotti PC, Mosca F, Gold DV, et al. Initial tumor targeting, biodistribution, and pharmacokinetic evaluation of the monoclonal antibody PAM4 in patients with pancreatic cancer. Cancer Res. 1995 Dec 1;55(23 Suppl):5911s-5915s.
Alisauskus R, Wong GY, Gold DV. Initial studies of monoclonal antibody PAM4 targeting to xenografted orthotopic pancreatic cancer. Cancer Res. 1995 Dec 1;55(23 Suppl):5743s-5748s.
Gold DV, Alisauskas R, Sharkey RM. Targeting of xenografted pancreatic cancer with a new monoclonal antibody, PAM4. Cancer Res. 1995 Mar 1;55(5):1105-10.
Gold DV, Lew K, Maliniak R, Hernandez M, Cardillo T. Characterization of monoclonal antibody PAM4 reactive with a pancreatic cancer mucin. Int J Cancer. 1994 Apr 15;57(2):204-10.

Responsible Party: Immunomedics, INc. ( William Wegener, MD, PhD )
Study ID Numbers: IM-T-hPAM4-02
Study First Received: January 8, 2008
Last Updated: January 8, 2009
ClinicalTrials.gov Identifier: NCT00603863  
Health Authority: United States: Food and Drug Administration

Keywords provided by Immunomedics, Inc.:
pancreatic cancer
hPAM4
MUC1 antibody
cancer of the pancreas

Study placed in the following topic categories:
Antibodies
Digestive System Diseases
Digestive System Neoplasms
Pancreatic Neoplasms
Endocrine System Diseases
Pancreatic Diseases
Gastrointestinal Neoplasms
Endocrinopathy
Gemcitabine
Pancrelipase
Immunoglobulins
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 14, 2009