Safety and Efficacy Study of 90Y-hPAM4 at Different Doses

NCT ID: NCT00597129

Last Updated: 2021-08-19

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

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-08-31

Study Completion Date

2007-10-31

Brief Summary

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Safety study to determine highest dose of 90Y-hPAM4 can be safety administered

Detailed Description

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radiolabeled anti-MUC1 humanized antibody) administered intravenously as a single dose to patients with locally advanced and/or metastatic pancreatic cancer. The primary objective is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of 90Y-hPAM4 in this population. Secondary objectives include the assessment of tumor targeting, biodistribution, organ dosimetry and pharmacokinetics (PK) of 90Y-hPAM4 as determined by pre-therapy administration of 111In-hPAM4, the assessment of the antigenicity of 90Y-hPAM4, as determined by development of human anti-humanized antibodies (HAHA), and to obtain preliminary information on the efficacy of single dose 90Y-hPAM4 in this patient population.

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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Multi Dose levels

different doses of 90YhPAM4 will be given only once.

Group Type EXPERIMENTAL

90Y-hPAM4

Intervention Type BIOLOGICAL

Single dose of 90Y-hPAM4 will be given and all patients will be followed for 12 weeks.

Interventions

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90Y-hPAM4

Single dose of 90Y-hPAM4 will be given and all patients will be followed for 12 weeks.

Intervention Type BIOLOGICAL

Other Intervention Names

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111-IN-hPAM4 MUC-1 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, Stage III or IV pancreatic adenocarcinoma.
* Patients with Stage III (locally advanced) disease must have documented progression after failing primary therapy
* Patients with Stage IV (metastatic) disease must not have received more than one chemotherapy regimen.
* Measurable disease by CT, with at least on lesion \>1.5 cm in one dimension.
* Karnofsky performance status \> 70 % (Appendix A).
* Expected survival \> three months.
* At least 4 weeks beyond chemotherapy, radiotherapy, major surgery, other experimental treatments, 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 \> 10 g/dL, ANC \> 1,500 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 treatment with nitrosureas, actinomycin-D, radioimmunotherapy or other antibody-based therapies (murine, chimeric, humanized or human) 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
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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Immunomedics, Inc.

Principal Investigators

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William Wegener, MD, PhD

Role: STUDY_CHAIR

Gilead Sciences

Locations

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Goshen Cancer Center

Goshen, Indiana, United States

Site Status

Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

University of Medicine and Dentistry

Newark, New Jersey, United States

Site Status

Fox Chase Cancer 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, Karacay H, Cardillo TM, Newsome G, Goldenberg DM, Gold DV. Identification of a Mu-9 (anti-colon-specific antigen-p)-reactive peptide having homology to CA125 (MUC16). Int J Oncol. 2005 Jun;26(6):1591-6.

Reference Type BACKGROUND
PMID: 15870874 (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, Goldenberg DM, Sharkey RM. Localization of pancreatic cancer with radiolabeled monoclonal antibody PAM4. Crit Rev Oncol Hematol. 2001 Jul-Aug;39(1-2):147-54. doi: 10.1016/s1040-8428(01)00114-7.

Reference Type BACKGROUND
PMID: 11418312 (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-hPAM4-01

Identifier Type: -

Identifier Source: org_study_id

NCT00303680

Identifier Type: -

Identifier Source: nct_alias

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