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

BACKGROUND Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluat...

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Veröffentlicht in:Cancer Jg. 119; H. 24; S. 4268 - 4276
Hauptverfasser: Limaye, Sewanti Atul, Haddad, Robert I., Cilli, Fiona, Sonis, Stephen T., Colevas, A. Dimitrios, Brennan, Michael T., Hu, Kenneth S., Murphy, Barbara A.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Hoboken, NJ Wiley-Blackwell 15.12.2013
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ISSN:0008-543X, 1097-0142, 1097-0142
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Abstract BACKGROUND Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5‐fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained. METHODS A total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 × 1011, 6 × 1011, and 1.2 × 1012 colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted. RESULTS AG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013‐subjects versus placebo. All placebo subjects experienced ≥ 2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement. CONCLUSIONS AG013 was safe and well tolerated. Preliminary efficacy data support further study. Cancer 2013;119:4268–4276. © 2013 American Cancer Society. An oral rinse formulation of AG013 containing recombinant Lactococcus lactis secreting the mucosal protectant human Trefoil Factor 1 (hTFF1) was evaluated in a phase 1b study in subjects with locally advanced head and neck cancer who were receiving induction chemotherapy with cisplatin, 5‐fluorouracil with or without docetaxel. AG013 rinse was found to be safe and tolerable with preliminary efficacy data warranting further study.
AbstractList Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5-fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained. A total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 × 10(11) , 6 × 10(11) , and 1.2 × 10(12) colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted. AG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013-subjects versus placebo. All placebo subjects experienced ≥ 2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement. AG013 was safe and well tolerated. Preliminary efficacy data support further study.
An oral rinse formulation of AG013 containing recombinant Lactococcus lactis secreting the mucosal protectant human Trefoil Factor 1 (hTFF1) was evaluated in a phase 1b study in subjects with locally advanced head and neck cancer who were receiving induction chemotherapy with cisplatin, 5‐fluorouracil with or without docetaxel. AG013 rinse was found to be safe and tolerable with preliminary efficacy data warranting further study.
BACKGROUND Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5‐fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained. METHODS A total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 × 1011, 6 × 1011, and 1.2 × 1012 colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted. RESULTS AG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013‐subjects versus placebo. All placebo subjects experienced ≥ 2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement. CONCLUSIONS AG013 was safe and well tolerated. Preliminary efficacy data support further study. Cancer 2013;119:4268–4276. © 2013 American Cancer Society. An oral rinse formulation of AG013 containing recombinant Lactococcus lactis secreting the mucosal protectant human Trefoil Factor 1 (hTFF1) was evaluated in a phase 1b study in subjects with locally advanced head and neck cancer who were receiving induction chemotherapy with cisplatin, 5‐fluorouracil with or without docetaxel. AG013 rinse was found to be safe and tolerable with preliminary efficacy data warranting further study.
Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5-fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained.BACKGROUNDOral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5-fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained.A total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 × 10(11) , 6 × 10(11) , and 1.2 × 10(12) colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted.METHODSA total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 × 10(11) , 6 × 10(11) , and 1.2 × 10(12) colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted.AG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013-subjects versus placebo. All placebo subjects experienced ≥ 2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement.RESULTSAG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013-subjects versus placebo. All placebo subjects experienced ≥ 2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement.AG013 was safe and well tolerated. Preliminary efficacy data support further study.CONCLUSIONSAG013 was safe and well tolerated. Preliminary efficacy data support further study.
Author Cilli, Fiona
Haddad, Robert I.
Limaye, Sewanti Atul
Brennan, Michael T.
Colevas, A. Dimitrios
Murphy, Barbara A.
Sonis, Stephen T.
Hu, Kenneth S.
Author_xml – sequence: 1
  givenname: Sewanti Atul
  surname: Limaye
  fullname: Limaye, Sewanti Atul
  organization: Dana‐Farber Cancer Institute/Harvard Medical School
– sequence: 2
  givenname: Robert I.
  surname: Haddad
  fullname: Haddad, Robert I.
  organization: Dana‐Farber Cancer Institute/Harvard Medical School
– sequence: 3
  givenname: Fiona
  surname: Cilli
  fullname: Cilli, Fiona
  organization: ActoGeniX NV
– sequence: 4
  givenname: Stephen T.
  surname: Sonis
  fullname: Sonis, Stephen T.
  organization: Biomodels LLC
– sequence: 5
  givenname: A. Dimitrios
  surname: Colevas
  fullname: Colevas, A. Dimitrios
  organization: Stanford University
– sequence: 6
  givenname: Michael T.
  surname: Brennan
  fullname: Brennan, Michael T.
  organization: Carolinas Medical Center
– sequence: 7
  givenname: Kenneth S.
  surname: Hu
  fullname: Hu, Kenneth S.
  organization: Beth Israel Medical Center
– sequence: 8
  givenname: Barbara A.
  surname: Murphy
  fullname: Murphy, Barbara A.
  organization: Vanderbilt University Medical Center
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https://www.ncbi.nlm.nih.gov/pubmed/24114811$$D View this record in MEDLINE/PubMed
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CODEN CANCAR
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Copyright 2013 American Cancer Society
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2013 American Cancer Society.
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Issue 24
Keywords Human
oral mucositis
Stomatology
Toxicity
Multicenter study
Single dose
Malignant tumor
Induction treatment
safety and tolerability
Increasing dose
Stomatitis
mouth rinse
Cancerology
Sequential
Placebo
ENT disease
Head and neck cancer
Oral cavity disease
Locally advanced stage
induction chemotherapy
Cancer
head and neck cancer
Language English
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2013 American Cancer Society.
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PublicationTitle Cancer
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PublicationYear 2013
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Snippet BACKGROUND Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and...
An oral rinse formulation of AG013 containing recombinant Lactococcus lactis secreting the mucosal protectant human Trefoil Factor 1 (hTFF1) was evaluated in a...
Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of...
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SubjectTerms Administration, Topical
Adolescent
Adult
Aged
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - adverse effects
Biological and medical sciences
Female
head and neck cancer
Head and Neck Neoplasms - drug therapy
Head and Neck Neoplasms - metabolism
Head and Neck Neoplasms - microbiology
Humans
Induction Chemotherapy
Lactococcus lactis - genetics
Lactococcus lactis - metabolism
Male
Medical sciences
Middle Aged
Mouth Mucosa - drug effects
Mouth Mucosa - microbiology
mouth rinse
Mouthwashes - administration & dosage
Mouthwashes - adverse effects
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
oral mucositis
Otorhinolaryngology (head neck, general aspects and miscellaneous)
Otorhinolaryngology. Stomatology
safety and tolerability
Stomatitis - chemically induced
Stomatitis - drug therapy
Stomatitis - microbiology
Stomatitis - prevention & control
Trefoil Factor-1
Tumor Suppressor Proteins - administration & dosage
Tumor Suppressor Proteins - biosynthesis
Tumor Suppressor Proteins - pharmacokinetics
Tumors
Young Adult
Title 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
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