Phase I clinical trial of the chimeric monoclonal antibody (c30.6) in patients with metastatic colorectal cancer

Robyn L. Ward, Deborah Packham, Anne M. Smythe, Jayne Murray, Peter Anderson-Stewart, Neil Kitchen, Rosyln Muirhead, Peter Phillips, Peter Gray, Grant Bigg-Wither, Krishnan Prabakaran, Judy Freund, Michael Fullham, Michele Rule, David Dalley, Alan Meagher, Nicholas J. Hawkins, Glenn M. Smith

Research output: Contribution to journalArticle

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Abstract

The murine antibody 30.6 recognizes an antigen that is expressed on a high proportion of colorectal carcinomas and their metastases. We report the results of single-dose escalation studies of the chimeric 30.6 (c30.6) monoclonal antibody in metastatic colorectal cancer, to evaluate its safety, pharmacokinetics, and biodistribution. Recombinant c30.6 (IgG1κ) antibody was secreted from Chinese hamster ovary cells and purified by a multi-step chromatography process. Seventeen patients with metastatic colorectal cancer were enrolled in this dose escalation study. The first four patients were treated with 3 mg of 123I-labeled c30.6, whereas the next 13 received a single dose of unlabeled antibody (maximum dose, 50 mg/m2). The most frequent side effect was a novel syndrome of severe burning and erythema of the face, chest, neck, ears, palms, soles, and genitalia. The frequency of this syndrome was markedly reduced in those patients premedicated with high doses of histamine receptor 1 and histamine receptor 2 blockers. Other side effects were mild and predictable. Bio-distribution studies showed a rapid and intensive hepatic uptake. At the 50 mg/m2level the half-life and maximum serum concentration were 81 ± 15 h and 7.9 μg/ml, respectively. One patient developed a low-level human anti-c30.6 response. Tumor response was assessed by computed tomography, positron emission tomography scanning, and serial carcinoembryonic antigen measurements. There were no partial responses, although positron emission tomography scanning demonstrated some reduction in tumor activity in three individuals. The chimerized c30.6 antibody is not immunogenic in humans and appears worthy of further study. It does, however, produce a unique profile of side effects that can be well controlled with premedication.

Original languageEnglish (US)
Pages (from-to)4674-4683
Number of pages10
JournalClinical Cancer Research
Volume6
Issue number12
StatePublished - Jan 1 2000

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Clinical Trials, Phase I
Colorectal Neoplasms
Monoclonal Antibodies
Histamine Receptors
Antibodies
Genitalia
Premedication
Carcinoembryonic Antigen
Erythema
Cricetulus
Positron-Emission Tomography
Ear
Half-Life
Chromatography
Ovary
Neoplasms
Neck
Thorax
Pharmacokinetics
Immunoglobulin G

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ward, R. L., Packham, D., Smythe, A. M., Murray, J., Anderson-Stewart, P., Kitchen, N., ... Smith, G. M. (2000). Phase I clinical trial of the chimeric monoclonal antibody (c30.6) in patients with metastatic colorectal cancer. Clinical Cancer Research, 6(12), 4674-4683.

Phase I clinical trial of the chimeric monoclonal antibody (c30.6) in patients with metastatic colorectal cancer. / Ward, Robyn L.; Packham, Deborah; Smythe, Anne M.; Murray, Jayne; Anderson-Stewart, Peter; Kitchen, Neil; Muirhead, Rosyln; Phillips, Peter; Gray, Peter; Bigg-Wither, Grant; Prabakaran, Krishnan; Freund, Judy; Fullham, Michael; Rule, Michele; Dalley, David; Meagher, Alan; Hawkins, Nicholas J.; Smith, Glenn M.

In: Clinical Cancer Research, Vol. 6, No. 12, 01.01.2000, p. 4674-4683.

Research output: Contribution to journalArticle

Ward, RL, Packham, D, Smythe, AM, Murray, J, Anderson-Stewart, P, Kitchen, N, Muirhead, R, Phillips, P, Gray, P, Bigg-Wither, G, Prabakaran, K, Freund, J, Fullham, M, Rule, M, Dalley, D, Meagher, A, Hawkins, NJ & Smith, GM 2000, 'Phase I clinical trial of the chimeric monoclonal antibody (c30.6) in patients with metastatic colorectal cancer', Clinical Cancer Research, vol. 6, no. 12, pp. 4674-4683.
Ward RL, Packham D, Smythe AM, Murray J, Anderson-Stewart P, Kitchen N et al. Phase I clinical trial of the chimeric monoclonal antibody (c30.6) in patients with metastatic colorectal cancer. Clinical Cancer Research. 2000 Jan 1;6(12):4674-4683.
Ward, Robyn L. ; Packham, Deborah ; Smythe, Anne M. ; Murray, Jayne ; Anderson-Stewart, Peter ; Kitchen, Neil ; Muirhead, Rosyln ; Phillips, Peter ; Gray, Peter ; Bigg-Wither, Grant ; Prabakaran, Krishnan ; Freund, Judy ; Fullham, Michael ; Rule, Michele ; Dalley, David ; Meagher, Alan ; Hawkins, Nicholas J. ; Smith, Glenn M. / Phase I clinical trial of the chimeric monoclonal antibody (c30.6) in patients with metastatic colorectal cancer. In: Clinical Cancer Research. 2000 ; Vol. 6, No. 12. pp. 4674-4683.
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AU - Kitchen, Neil

AU - Muirhead, Rosyln

AU - Phillips, Peter

AU - Gray, Peter

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AU - Prabakaran, Krishnan

AU - Freund, Judy

AU - Fullham, Michael

AU - Rule, Michele

AU - Dalley, David

AU - Meagher, Alan

AU - Hawkins, Nicholas J.

AU - Smith, Glenn M.

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N2 - The murine antibody 30.6 recognizes an antigen that is expressed on a high proportion of colorectal carcinomas and their metastases. We report the results of single-dose escalation studies of the chimeric 30.6 (c30.6) monoclonal antibody in metastatic colorectal cancer, to evaluate its safety, pharmacokinetics, and biodistribution. Recombinant c30.6 (IgG1κ) antibody was secreted from Chinese hamster ovary cells and purified by a multi-step chromatography process. Seventeen patients with metastatic colorectal cancer were enrolled in this dose escalation study. The first four patients were treated with 3 mg of 123I-labeled c30.6, whereas the next 13 received a single dose of unlabeled antibody (maximum dose, 50 mg/m2). The most frequent side effect was a novel syndrome of severe burning and erythema of the face, chest, neck, ears, palms, soles, and genitalia. The frequency of this syndrome was markedly reduced in those patients premedicated with high doses of histamine receptor 1 and histamine receptor 2 blockers. Other side effects were mild and predictable. Bio-distribution studies showed a rapid and intensive hepatic uptake. At the 50 mg/m2level the half-life and maximum serum concentration were 81 ± 15 h and 7.9 μg/ml, respectively. One patient developed a low-level human anti-c30.6 response. Tumor response was assessed by computed tomography, positron emission tomography scanning, and serial carcinoembryonic antigen measurements. There were no partial responses, although positron emission tomography scanning demonstrated some reduction in tumor activity in three individuals. The chimerized c30.6 antibody is not immunogenic in humans and appears worthy of further study. It does, however, produce a unique profile of side effects that can be well controlled with premedication.

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