Clinical trial NCT00603863: Safety and Efficacy Study of Different Doses of 90Y-hPAM4 Combined With Gemcitabine in Pancreatic Cancer
Official title: A Phase Ib/II Study of Fractionated 90Y-hPAM4 Plus Gemcitabine in Patients With Previously Untreated Advanced Pancreatic Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: pancreatic cancer
hPAM4
MUC1 antibody
cancer of the pancreas
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2008-01-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility 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 \> 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.

Primary outcomes:
measure: safety will be evaluated based upon physical examinations, hematology and chemistry laboratory testing as well as toxicity
timeFrame: over 12 weeks
Secondary outcomes:
measure: Efficacy and Clinical benefit measures such as quality of life, pain assessments, etc.
timeFrame: over 5 years
Other outcomes:
Locations:
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: Herbert Werthem College of Medicine/Jackson North Medical Center
state: Florida
city: Tampa
country: United States
facility: Moffit Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute/Emory University Hospital
state: Georgia
city: Goshen
country: United States
facility: Goshen Cancer Center
state: Indiana
city: New York
country: United States
facility: New York Presbyterian Hospital/Weill Cornell Medical Center
state: New York
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Medical Center
state: Pennsylvania
Study officials:
affiliation: Gilead Sciences
name: William Wegener, MD, PHD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.