Safety and Efficacy Study of Different Doses of 90Y-hPAM4 Combined With Gemcitabine in Pancreatic Cancer

NCT00603863 | Completed Phase 1

• 1 other identifier: IM-T-hPAM4-02
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Pancreatic Cancer

Keywords

pancreatic cancer; hPAM4; MUC1 antibody; cancer of the pancreas

Outcome Measures

Primary Outcomes (1)

• safety will be evaluated based upon physical examinations, hematology and chemistry laboratory testing as well as toxicity

  over 12 weeks

Secondary Outcomes (1)

• Efficacy and Clinical benefit measures such as quality of life, pain assessments, etc.

  over 5 years

Study Arms (1)

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)

Interventions

IMMU-107 (hPAM4) BIOLOGICAL

90Y-hPAM4 once weekly for 3 weeks gemcitabine once weekly for 4 weeks

Also known as: hPAM4, IMMU-107, 90Y-hPAM4, anti-mucin antibody

multiple dose levels

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \> 11 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (11)

Christiana Care Health Services

Newark, Delaware, 19718, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Herbert Werthem College of Medicine/Jackson North Medical Center

Miami, Florida, 33169, United States

Location

Moffit Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute/Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Goshen Cancer Center

Goshen, Indiana, 46526, United States

Location

New York Presbyterian Hospital/Weill Cornell Medical Center

New York, New York, 10021, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University Medical Center

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (15)

• 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. doi: 10.1158/1078-0432.CCR-07-1488.

  PMID: 18094420 BACKGROUND

• Modrak DE, Gold DV, Goldenberg DM. Sphingolipid targets in cancer therapy. Mol Cancer Ther. 2006 Feb;5(2):200-8. doi: 10.1158/1535-7163.MCT-05-0420.

  PMID: 16505092 BACKGROUND

• 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. doi: 10.1200/JCO.2005.02.8282. Epub 2005 Dec 12.

  PMID: 16344318 BACKGROUND

• 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. doi: 10.1158/0008-5472.CAN-04-2988.

  PMID: 15548711 BACKGROUND

• 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. doi: 10.1002/ijc.20004.

  PMID: 14991585 BACKGROUND

• 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.

  PMID: 14506191 BACKGROUND

• 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. doi: 10.1159/000070658.

  PMID: 12743424 BACKGROUND

• 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. doi: 10.1016/s0959-8049(02)00700-1.

  PMID: 12565994 BACKGROUND

• 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. doi: 10.1002/ijc.1613.

  PMID: 11774294 BACKGROUND

• 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.

  PMID: 11595713 BACKGROUND

• 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. doi: 10.1002/(sici)1097-0215(19970516)71:43.0.co;2-e.

  PMID: 9178823 BACKGROUND

• 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.

  PMID: 7493369 BACKGROUND

• 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.

  PMID: 7493339 BACKGROUND

• 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.

  PMID: 7866995 BACKGROUND

• 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. doi: 10.1002/ijc.2910570213.

  PMID: 7512537 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• William Wegener, MD, PHD

  Gilead Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2008
• First Posted: January 29, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: December 1, 2013
• Last Updated: August 16, 2021

Record last verified: 2014-01

Locations

US (11)