The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: Results of a phase Ib dose-escalation, open-label study

L. R. Molife, P. C. Fong, L. Paccagnella, A. H.M. Reid, H. M. Shaw, L. Vidal, H. T. Arkenau, V. Karavasilis, T. A. Yap, D. Olmos, J. Spicer, S. Postel-Vinay, D. Yin, A. Lipton, L. Demers, K. Leitzel, A. Gualberto, J. S. De Bono

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Abstract

Background:This phase Ib trial assessed safety, tolerability, and maximum tolerated dose (MTD) of figitumumab (CP-751,871), a fully human monoclonal antibody targeting the insulin-like growth factor type 1 receptor (IGF-IR), in combination with docetaxel.Methods:Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mg m-2 docetaxel every 21 days. Safety, efficacy, pharmacokinetics (PKs), and biomarker responses were evaluated.Results:In 46 patients, no dose-limiting toxicities were attributable to the treatment combination. Grade 3 and 4 toxicities included neutropaenia (n=28), febrile neutropaenia (n=11), fatigue (n=10), leukopaenia (n=7), diarrhoea (n=5), hyperglycaemia, lymphopaenia, cellulitis, DVT, and pain (all n=1). The MTD was not reached. Four partial responses were observed; 12 patients had disease stabilisation of 6≥months. Pharmacokinetic and biomarker analyses showed a dose-dependent increase in plasma exposure, and complete sIGF-IR downregulation at doses of 3≥mg kg-1. Pharmacokinetics of docetaxel in combination was similar to when given alone. Out of 18 castration-resistant prostate cancer patients, 10 (56%) had 5 circulating tumour cells (CTCs) per 7.5 ml of blood at baseline: 6 out of 10 (60%) had a decline from ≥5 to <5 CTCs and 9 out of 10 (90%) had a ≥30% decline in CTCs after therapy.Conclusions:Figitumumab and docetaxel in combination are well tolerated. Further evaluation is warranted.

Original languageEnglish (US)
Pages (from-to)332-339
Number of pages8
JournalBritish Journal of Cancer
Volume103
Issue number3
DOIs
StatePublished - Jul 27 2010

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docetaxel
IGF Type 1 Receptor
Circulating Neoplastic Cells
Maximum Tolerated Dose
Pharmacokinetics
Neoplasms
Biomarkers
Safety
Lymphopenia
Cellulitis
Castration
Leukopenia
Cell- and Tissue-Based Therapy
Hyperglycemia
Fatigue
Diarrhea
Prostatic Neoplasms
Fever
Down-Regulation
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Molife, L. R. ; Fong, P. C. ; Paccagnella, L. ; Reid, A. H.M. ; Shaw, H. M. ; Vidal, L. ; Arkenau, H. T. ; Karavasilis, V. ; Yap, T. A. ; Olmos, D. ; Spicer, J. ; Postel-Vinay, S. ; Yin, D. ; Lipton, A. ; Demers, L. ; Leitzel, K. ; Gualberto, A. ; De Bono, J. S. / The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours : Results of a phase Ib dose-escalation, open-label study. In: British Journal of Cancer. 2010 ; Vol. 103, No. 3. pp. 332-339.
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title = "The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: Results of a phase Ib dose-escalation, open-label study",
abstract = "Background:This phase Ib trial assessed safety, tolerability, and maximum tolerated dose (MTD) of figitumumab (CP-751,871), a fully human monoclonal antibody targeting the insulin-like growth factor type 1 receptor (IGF-IR), in combination with docetaxel.Methods:Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mg m-2 docetaxel every 21 days. Safety, efficacy, pharmacokinetics (PKs), and biomarker responses were evaluated.Results:In 46 patients, no dose-limiting toxicities were attributable to the treatment combination. Grade 3 and 4 toxicities included neutropaenia (n=28), febrile neutropaenia (n=11), fatigue (n=10), leukopaenia (n=7), diarrhoea (n=5), hyperglycaemia, lymphopaenia, cellulitis, DVT, and pain (all n=1). The MTD was not reached. Four partial responses were observed; 12 patients had disease stabilisation of 6≥months. Pharmacokinetic and biomarker analyses showed a dose-dependent increase in plasma exposure, and complete sIGF-IR downregulation at doses of 3≥mg kg-1. Pharmacokinetics of docetaxel in combination was similar to when given alone. Out of 18 castration-resistant prostate cancer patients, 10 (56{\%}) had 5 circulating tumour cells (CTCs) per 7.5 ml of blood at baseline: 6 out of 10 (60{\%}) had a decline from ≥5 to <5 CTCs and 9 out of 10 (90{\%}) had a ≥30{\%} decline in CTCs after therapy.Conclusions:Figitumumab and docetaxel in combination are well tolerated. Further evaluation is warranted.",
author = "Molife, {L. R.} and Fong, {P. C.} and L. Paccagnella and Reid, {A. H.M.} and Shaw, {H. M.} and L. Vidal and Arkenau, {H. T.} and V. Karavasilis and Yap, {T. A.} and D. Olmos and J. Spicer and S. Postel-Vinay and D. Yin and A. Lipton and L. Demers and K. Leitzel and A. Gualberto and {De Bono}, {J. S.}",
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Molife, LR, Fong, PC, Paccagnella, L, Reid, AHM, Shaw, HM, Vidal, L, Arkenau, HT, Karavasilis, V, Yap, TA, Olmos, D, Spicer, J, Postel-Vinay, S, Yin, D, Lipton, A, Demers, L, Leitzel, K, Gualberto, A & De Bono, JS 2010, 'The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: Results of a phase Ib dose-escalation, open-label study', British Journal of Cancer, vol. 103, no. 3, pp. 332-339. https://doi.org/10.1038/sj.bjc.6605767

The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours : Results of a phase Ib dose-escalation, open-label study. / Molife, L. R.; Fong, P. C.; Paccagnella, L.; Reid, A. H.M.; Shaw, H. M.; Vidal, L.; Arkenau, H. T.; Karavasilis, V.; Yap, T. A.; Olmos, D.; Spicer, J.; Postel-Vinay, S.; Yin, D.; Lipton, A.; Demers, L.; Leitzel, K.; Gualberto, A.; De Bono, J. S.

In: British Journal of Cancer, Vol. 103, No. 3, 27.07.2010, p. 332-339.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours

T2 - Results of a phase Ib dose-escalation, open-label study

AU - Molife, L. R.

AU - Fong, P. C.

AU - Paccagnella, L.

AU - Reid, A. H.M.

AU - Shaw, H. M.

AU - Vidal, L.

AU - Arkenau, H. T.

AU - Karavasilis, V.

AU - Yap, T. A.

AU - Olmos, D.

AU - Spicer, J.

AU - Postel-Vinay, S.

AU - Yin, D.

AU - Lipton, A.

AU - Demers, L.

AU - Leitzel, K.

AU - Gualberto, A.

AU - De Bono, J. S.

PY - 2010/7/27

Y1 - 2010/7/27

N2 - Background:This phase Ib trial assessed safety, tolerability, and maximum tolerated dose (MTD) of figitumumab (CP-751,871), a fully human monoclonal antibody targeting the insulin-like growth factor type 1 receptor (IGF-IR), in combination with docetaxel.Methods:Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mg m-2 docetaxel every 21 days. Safety, efficacy, pharmacokinetics (PKs), and biomarker responses were evaluated.Results:In 46 patients, no dose-limiting toxicities were attributable to the treatment combination. Grade 3 and 4 toxicities included neutropaenia (n=28), febrile neutropaenia (n=11), fatigue (n=10), leukopaenia (n=7), diarrhoea (n=5), hyperglycaemia, lymphopaenia, cellulitis, DVT, and pain (all n=1). The MTD was not reached. Four partial responses were observed; 12 patients had disease stabilisation of 6≥months. Pharmacokinetic and biomarker analyses showed a dose-dependent increase in plasma exposure, and complete sIGF-IR downregulation at doses of 3≥mg kg-1. Pharmacokinetics of docetaxel in combination was similar to when given alone. Out of 18 castration-resistant prostate cancer patients, 10 (56%) had 5 circulating tumour cells (CTCs) per 7.5 ml of blood at baseline: 6 out of 10 (60%) had a decline from ≥5 to <5 CTCs and 9 out of 10 (90%) had a ≥30% decline in CTCs after therapy.Conclusions:Figitumumab and docetaxel in combination are well tolerated. Further evaluation is warranted.

AB - Background:This phase Ib trial assessed safety, tolerability, and maximum tolerated dose (MTD) of figitumumab (CP-751,871), a fully human monoclonal antibody targeting the insulin-like growth factor type 1 receptor (IGF-IR), in combination with docetaxel.Methods:Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mg m-2 docetaxel every 21 days. Safety, efficacy, pharmacokinetics (PKs), and biomarker responses were evaluated.Results:In 46 patients, no dose-limiting toxicities were attributable to the treatment combination. Grade 3 and 4 toxicities included neutropaenia (n=28), febrile neutropaenia (n=11), fatigue (n=10), leukopaenia (n=7), diarrhoea (n=5), hyperglycaemia, lymphopaenia, cellulitis, DVT, and pain (all n=1). The MTD was not reached. Four partial responses were observed; 12 patients had disease stabilisation of 6≥months. Pharmacokinetic and biomarker analyses showed a dose-dependent increase in plasma exposure, and complete sIGF-IR downregulation at doses of 3≥mg kg-1. Pharmacokinetics of docetaxel in combination was similar to when given alone. Out of 18 castration-resistant prostate cancer patients, 10 (56%) had 5 circulating tumour cells (CTCs) per 7.5 ml of blood at baseline: 6 out of 10 (60%) had a decline from ≥5 to <5 CTCs and 9 out of 10 (90%) had a ≥30% decline in CTCs after therapy.Conclusions:Figitumumab and docetaxel in combination are well tolerated. Further evaluation is warranted.

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U2 - 10.1038/sj.bjc.6605767

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