Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy

Cancer

Volumn 119, Issue 24, 2013, Pages 4268-4276

  Limaye, Sewanti Atul ^a   Haddad, Robert I ^a   Cilli, Fiona ^b   Sonis, Stephen T ^c,d   Colevas, A Dimitrios ^e   Brennan, Michael T ^f   Hu, Kenneth S ^g   Murphy, Barbara A ^h  

^a HARVARD MEDICAL SCHOOL   (United States)

^b ActoGeniX NV   (Belgium)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d Biomodels   (United States)

^e STANFORD UNIVERSITY   (United States)

^f CAROLINAS MEDICAL CENTER   (United States)

^g BETH ISRAEL MEDICAL CENTER   (United States)

^h VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

head and neck cancer; induction chemotherapy; mouth rinse; oral mucositis; safety and tolerability

Indexed keywords

AG 013; CISPLATIN; DOCETAXEL; FLUOROURACIL; MOUTHWASH; OPIATE; PLACEBO; PROTECTIVE AGENT; TREFOIL FACTOR 1; TREFOIL PEPTIDE; UNCLASSIFIED DRUG;

ABNORMAL LABORATORY RESULT; ADULT; ADVANCED CANCER; AMBULATORY CARE; ARTICLE; BACTERIAL COUNT; CLINICAL ARTICLE; COLONY FORMING UNIT; CONTROLLED STUDY; DIARRHEA; DISEASE CLASSIFICATION; DOSAGE SCHEDULE COMPARISON; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG TOLERABILITY; DRUG USE; DRUG WITHDRAWAL; EMERGENCY WARD; FATIGUE; FEMALE; FOLLOW UP; GENETIC ENGINEERING; HEAD AND NECK CANCER; HUMAN; INDUCTION CHEMOTHERAPY; LACTOCOCCUS LACTIS; MALE; MIDDLE AGED; MOUTH FLORA; MOUTH MUCOSA; MOUTH PAIN; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; ORAL MUCOSITIS; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SALIVA LEVEL; SEPSIS; SINGLE BLIND PROCEDURE; SORE THROAT; STOMACH TUBE; STOMATITIS; YOUNG ADULT;

HEAD AND NECK CANCER; INDUCTION CHEMOTHERAPY; MOUTH RINSE; ORAL MUCOSITIS; SAFETY AND TOLERABILITY;

ADMINISTRATION, TOPICAL; ADOLESCENT; ADULT; AGED; ANTINEOPLASTIC AGENTS; FEMALE; HEAD AND NECK NEOPLASMS; HUMANS; INDUCTION CHEMOTHERAPY; LACTOCOCCUS LACTIS; MALE; MIDDLE AGED; MOUTH MUCOSA; MOUTHWASHES; STOMATITIS; TUMOR SUPPRESSOR PROTEINS; YOUNG ADULT;

EID: 84889883370     PISSN: 0008543X     EISSN: 10970142     Source Type: Journal    
DOI: 10.1002/cncr.28365     Document Type: Article

References (19)

1. Keefe DM, Schubert MM, Elting LS, et al. Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer. 2007; 109: 820-831.
2. Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007; 357: 1705-1715.
3. Vermorken JB, Remenar E, van Herpen C, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007; 357: 1695-1704.
4. Rosen LS, Abdi E, Davis ID, et al. Palifermin reduces the incidence of oral mucositis in patients with metastatic colorectal cancer treated with fluorouracil-based chemotherapy. J Clin Oncol. 2006; 24: 5194-5200.
5. Hoffmann W,. Trefoil factor family (TFF) peptides: regulators of mucosal regeneration and repair, and more. Peptides. 2004; 25: 727-730.
6. Poulsen SS, Thulesen J, Hartmann B, Kissow HL, Nexo E, Thim L,. Injected TFF1 and TFF3 bind to TFF2-immunoreactive cells in the gastrointestinal tract in rats. Regul Pept. 2003; 115: 91-99.
7. Taupin D, Podolsky DK,. Trefoil factors: initiators of mucosal healing. Nat Rev Mol Cell Biol. 2003; 4: 721-732.
8. Devine DA, High AS, Owen PJ, Poulsom R, Bonass WA,. Trefoil factor expression in normal and diseased human salivary glands. Hum Pathol. 2000; 31: 509-515.
9. Beck PL, Wong JF, Li Y, et al. Chemotherapy- and radiotherapy-induced intestinal damage is regulated by intestinal trefoil factor. Gastroenterology. 2004; 126: 796-808.
10. Peterson DE, Barker NP, Akhmadullina LI, et al. Phase II, randomized, double-blind, placebo-controlled study of recombinant human intestinal trefoil factor oral spray for prevention of oral mucositis in patients with colorectal cancer who are receiving fluorouracil-based chemotherapy. J Clin Oncol. 2009; 27: 4333-4338.
11. Steidler L, Hans W, Schotte L, et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science. 2000; 289: 1352-1355.
12. Steidler L, Neirynck S, Huyghebaert N, et al. Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nat Biotechnol. 2003; 21: 785-789.
13. Vandenbroucke K, Hans W, Van Huysse J, et al. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology. 2004; 127: 502-513.
14. Caluwaerts S, Vandenbroucke K, Steidler L, et al. AG013, a mouth rinse formulation of Lactococcus lactis secreting human Trefoil Factor 1, provides a safe and efficacious therapeutic tool for treating oral mucositis. Oral Oncol. 2010; 46: 564-570.
15. Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003; 349: 2091-2098.
16. Braat H, Rottiers P, Hommes DW, et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin Gastroenterol Hepatol. 2006; 4: 754-759.
17. ICH. Efficacy Guidelines: Good Clinical Practice E6. http://www.ich.org/ products/guidelines/efficacy/efficacy-single/article/good-clinical-practice. html. Accessed August 26, 2013.
18. Stiff PJ, Emmanouilides C, Bensinger WI, et al. Palifermin reduces patient-reported mouth and throat soreness and improves patient functioning in the hematopoietic stem-cell transplantation setting. J Clin Oncol. 2006; 24: 5186-5193.
19. ActoGeniX announces positive results from a phase 1 PK study of AG013 for the prevention of oral mucositis in cancer patients [press release]. Ghent, Belgium: ActoGeniX; 2012. Released August 22, 2012.