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

NCT ID: NCT00603863

Last Updated: 2021-08-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-01-31

Study Completion Date

2013-12-31

Brief Summary

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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.

Detailed Description

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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 once weekly 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 another 90YhPAM4 treatment cycle, maintenance gemcitabine or for a maximum period of 12 weeks.

Conditions

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Pancreatic Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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multiple dose levels

1 of 3 different dose levels of 90Y-hPAM4 given once weekly for 3 weeks along with 4 weekly doses of gemcitabine.

Group Type EXPERIMENTAL

IMMU-107 (hPAM4)

Intervention Type BIOLOGICAL

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

Interventions

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IMMU-107 (hPAM4)

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

Intervention Type BIOLOGICAL

Other Intervention Names

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hPAM4 IMMU-107 90Y-hPAM4 anti-mucin antibody

Eligibility Criteria

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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 \> 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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William Wegener, MD, PHD

Role: STUDY_CHAIR

Gilead Sciences

Locations

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Christiana Care Health Services

Newark, Delaware, United States

Site Status

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Herbert Werthem College of Medicine/Jackson North Medical Center

Miami, Florida, United States

Site Status

Moffit Cancer Center

Tampa, Florida, United States

Site Status

Winship Cancer Institute/Emory University Hospital

Atlanta, Georgia, United States

Site Status

Goshen Cancer Center

Goshen, Indiana, United States

Site Status

New York Presbyterian Hospital/Weill Cornell Medical Center

New York, New York, United States

Site Status

Mt. Sinai Medical Center

New York, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Thomas Jefferson University Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 18094420 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16505092 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16344318 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15548711 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14991585 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14506191 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12743424 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12565994 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11774294 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11595713 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9178823 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7493369 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7493339 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7866995 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7512537 (View on PubMed)

Other Identifiers

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IM-T-hPAM4-02

Identifier Type: -

Identifier Source: org_study_id

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