Phase 3 Trial of 90Y-Clivatuzumab Tetraxetan & Gemcitabine vs Placebo & Gemcitabine in Metastatic Pancreatic Cancer

Pancreatic Cancer Clinical Trial

— PANCRIT®-1  

Official title:

An International, Multi-Center, Double-Blind, Randomized, Phase III Trial of 90Y-Clivatuzumab Tetraxetan Plus Low-Dose Gemcitabine Versus Placebo Plus Low-Dose Gemcitabine in Patients With Metastatic (Stage IV) Pancreatic Adenocarcinoma Who Received at Least Two Prior Treatments (PANCRIT-1)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01956812
• Other study ID #: IMMU-107-04
• Status: Terminated
• Phase: Phase 3
• Start date: December 2013
• Est. completion date: November 2016

Study information

• Verified date: March 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The is a double-blind, randomized phase 3 study of 90Y-clivatuzumab tetraxetan with low-dose gemcitabine, versus placebo and low-dose gemcitabine in metastatic pancreatic cancer patients who have progressed on at least 2 prior therapies for metastatic cancer (1 of which was a gemcitabine-containing regimen).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 334
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• Metastatic disease
• Received at least two prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease.
• At least one of the prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease must have contained gemcitabine and have met

the following criteria:

• Completed at least one cycle of the treatment
• Received gemcitabine administered at a minimum dose of 800 mg/m2 per week in the first cycle of treatment
• Progressed while receiving this gemcitabine regimen or within 3 months of completing gemcitabine
• Progression was documented,
• Preferentially radiologically by tumor growth or new lesions, or by
• Clear symptomatic deterioration supported by at least two of the following clinical criteria: = 10% worsening in KPS or = 1 worsening in ECOG; increasing weakness or fatigue; progressive weight loss; new/worsening pain requiring increased pain medication; new/worsening jaundice, nausea, or vomiting; new/worsening ascites or pleural effusions; other physical or laboratory findings consistent with disease progression.
• KPS >/= 70
• Adequate bone marrow function
• Adequate hepatic function
• Adequate renal function

Exclusion Criteria:

• CNS metastatic disease
• Bulky disease (any single mass >10 cm). ->Grade 2 nausea or vomiting, and/or signs of intestinal obstruction.
• Prior external beam irradiation to a field that includes more than 30% of the red bone marrow.
• Patients with clinically significant severe cardiorespiratory disease. Please consult with the clinical trial site for the full detailed list of specific inclusion/exclusion criteria.

Related Conditions & MeSH terms

• Metastatic Pancreatic Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• IMMU-107
Arm A: gemcitabine 200 mg/m2 administered weekly x 4 and IMMU-107 administered weekly x 3 for multiple cycles
• placebo
placebo weekly x 3 and gemcitabine 200 mg/m2 weekly x 4 for multiple cycles
• Gemcitabine
Gemcitabine, 200 mg/m2, given weekly x 4 in both arms

Locations

Country	Name	City	State
Austria	Krankenhaus der Elisabethinen Linz	Linz
Austria	Medical University Vienna	Vienna
Belgium	University Hospital Leuven	Leuven
Canada	Centre Hospitalier Université de Sherbrooke	Sherbrooke	Quebec
Canada	Cancer Care Manitoba	Winnepeg	Manitoba
France	Institut Bergonie	Bordeaux	Cedex
France	Centre Léon Bérard Cancerologie Medicale	Lyon
France	Institut Paoli-Calmettes	Marseille
France	Institut Paoli-Calmettes	Marseille	Cedex 9
France	CRLC Val D'Aurelle	Montpellier
France	CRLC Val D'Aurelle	Montpellier Cedex 5
France	ICO René Gauducheau	Nantes	Cedex 1
France	Hopital Cochin	Paris
Israel	Soroka Medical Center	Beer Sheva
Israel	Rambam Medical Center	Haifa
Poland	Centrum Onkologii Instytut im. M. Sklodowskiej-Curie - Warszawa	Warszawa
Spain	Hospital Vall D'Hebrón	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Sant Joan de Reu	Reus	Tarragona
Spain	Hospital Miguel Servet	Zaragoza
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	Ashland-Bellefonte Cancer Center	Ashland	Kentucky
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho
United States	University of North Carolina Hospitals, Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	The Ohio State University - Comprehensive Cancer Center	Columbus	Ohio
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Michael and Dianne Bienes Comprehensive Cancer Center - Holy Cross Hospital	Fort Lauderdale	Florida
United States	Banner MD Anderson	Gilbert	Arizona
United States	Indiana University Health Goshen Center for Cancer Care	Goshen	Indiana
United States	The Pennsylvania State University (Penn State) Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Oncology Consultants	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Center for Biomedical Research	Knoxville	Tennessee
United States	University of Tennessee Medical Center, Cancer Institute	Knoxville	Tennessee
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Pacific Shores Medical Group	Long Beach	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Texas Oncology - McAllen	McAllen	Texas
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Presbyterian Hospital/Weill Cornell Medical Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Whittingham Cancer Center	Norwalk	Connecticut
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Oncology Hematology West P.C. dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center/Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	University of Rochester Medical Center	Rochester	New York
United States	University of Washington	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Texas Oncology - Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Israel,  Poland,  Spain, 

References & Publications (19)

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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. — View 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. — View Citation

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. — View 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. — View Citation

Gold DV, Gaedcke J, Ghadimi BM, Goggins M, Hruban RH, Liu M, Newsome G, Goldenberg DM. PAM4 enzyme immunoassay alone and in combination with CA 19-9 for the detection of pancreatic adenocarcinoma. Cancer. 2013 Feb 1;119(3):522-8. doi: 10.1002/cncr.27762. Epub 2012 Aug 16. — View Citation

Gold DV, Goggins M, Modrak DE, Newsome G, Liu M, Shi C, Hruban RH, Goldenberg DM. Detection of early-stage pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2786-94. doi: 10.1158/1055-9965.EPI-10-0667. Epub 2010 Sep 1. — View Citation

Gold DV, Goldenberg DM, Karacay H, Rossi EA, Chang CH, Cardillo TM, McBride WJ, Sharkey RM. A novel bispecific, trivalent antibody construct for targeting pancreatic carcinoma. Cancer Res. 2008 Jun 15;68(12):4819-26. doi: 10.1158/0008-5472.CAN-08-0232. — View 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. — View 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. — View 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. — View 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. Epub 2005 Dec 12. — View Citation

Gold DV, Newsome G, Liu D, Goldenberg DM. Mapping PAM4 (clivatuzumab), a monoclonal antibody in clinical trials for early detection and therapy of pancreatic ductal adenocarcinoma, to MUC5AC mucin. Mol Cancer. 2013 Nov 20;12(1):143. doi: 10.1186/1476-4598-12-143. — View 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. — View Citation

Gulec SA, Cohen SJ, Pennington KL, Zuckier LS, Hauke RJ, Horne H, Wegener WA, Teoh N, Gold DV, Sharkey RM, Goldenberg DM. Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial. Clin Cancer Res. 2011 Jun 15;17(12):4091-100. doi: 10.1158/1078-0432.CCR-10-2579. Epub 2011 Apr 28. — View 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. — View Citation

Ocean AJ, Pennington KL, Guarino MJ, Sheikh A, Bekaii-Saab T, Serafini AN, Lee D, Sung MW, Gulec SA, Goldsmith SJ, Manzone T, Holt M, O'Neil BH, Hall N, Montero AJ, Kauh J, Gold DV, Horne H, Wegener WA, Goldenberg DM. Fractionated radioimmunotherapy with (90) Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A phase 1 trial. Cancer. 2012 Nov 15;118(22):5497-506. doi: 10.1002/cncr.27592. Epub 2012 May 8. — View Citation

Sharkey RM, Karacay H, Govindan SV, Goldenberg DM. Combination radioimmunotherapy and chemoimmunotherapy involving different or the same targets improves therapy of human pancreatic carcinoma xenograft models. Mol Cancer Ther. 2011 Jun;10(6):1072-81. doi: 10.1158/1535-7163.MCT-11-0115. Epub 2011 Apr 5. — View Citation

Tokh M, Bathini V, Saif MW. First-line treatment of metastatic pancreatic cancer. JOP. 2012 Mar 10;13(2):159-62. Review. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall survival		24 months
Secondary	Overall survival		3, 6 and 12 months
Secondary	Objective tumor response		24 months
Secondary	Progression free survival		24 months
Secondary	Clinical benefit	quality of life will be assessed over 24 months using the FACT-hepatopancreatic form	24 months