Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma

Michael B. Atkins, Manuel Hidalgo, Walter M. Stadler, Theodore Logan, Janice P. Dutcher, Gary R. Hudes, Young Park, Song Heng Liou, Bonnie Marshall, Joseph P. Boni, Gary Dukart, Matthew L. Sherman

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Abstract

Purpose: To evaluate the efficacy, safety, and pharmacokinetics of multiple doses of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma (RCC). Patients and Methods: Patients (n = 111) were randomly assigned to receive 25, 75, or 250 mg CCI-779 weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, survival, and adverse events. Blood samples were collected to determine CCI-779 pharmacokinetics. Results: CCI-779 produced an objective response rate of 7% (one complete response and seven partial responses) and minor responses in 26% of these advanced RCC patients. Median time to tumor progression was 5.8 months and median survival was 15.0 months. The most frequently occurring CCI-779-related adverse events of all grades were maculopapular rash (76%), mucositis (70%), asthenia (50%), and nausea (43%). The most frequently occurring grade 3 or 4 adverse events were hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), and hypertriglyceridemia (6%). Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level. Patients were retrospectively classified into good-, intermediate-, or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa. Within each risk group, the median survivals of patients at each dose level were similar. Conclusion: In patients with advanced RCC, CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested.

Original languageEnglish (US)
Pages (from-to)909-918
Number of pages10
JournalJournal of Clinical Oncology
Volume22
Issue number5
DOIs
StatePublished - 2004

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Sirolimus
Renal Cell Carcinoma
Phosphotransferases
Survival
Pharmacokinetics
Hypophosphatemia
Asthenia
Neoplasms
Mucositis
temsirolimus
Hypertriglyceridemia
Exanthema
Intravenous Infusions
Interferon-alpha
Hyperglycemia
Nausea
Reaction Time
Anemia
Safety
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. / Atkins, Michael B.; Hidalgo, Manuel; Stadler, Walter M.; Logan, Theodore; Dutcher, Janice P.; Hudes, Gary R.; Park, Young; Liou, Song Heng; Marshall, Bonnie; Boni, Joseph P.; Dukart, Gary; Sherman, Matthew L.

In: Journal of Clinical Oncology, Vol. 22, No. 5, 2004, p. 909-918.

Research output: Contribution to journalArticle

Atkins, MB, Hidalgo, M, Stadler, WM, Logan, T, Dutcher, JP, Hudes, GR, Park, Y, Liou, SH, Marshall, B, Boni, JP, Dukart, G & Sherman, ML 2004, 'Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma', Journal of Clinical Oncology, vol. 22, no. 5, pp. 909-918. https://doi.org/10.1200/JCO.2004.08.185
Atkins, Michael B. ; Hidalgo, Manuel ; Stadler, Walter M. ; Logan, Theodore ; Dutcher, Janice P. ; Hudes, Gary R. ; Park, Young ; Liou, Song Heng ; Marshall, Bonnie ; Boni, Joseph P. ; Dukart, Gary ; Sherman, Matthew L. / Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 5. pp. 909-918.
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abstract = "Purpose: To evaluate the efficacy, safety, and pharmacokinetics of multiple doses of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma (RCC). Patients and Methods: Patients (n = 111) were randomly assigned to receive 25, 75, or 250 mg CCI-779 weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, survival, and adverse events. Blood samples were collected to determine CCI-779 pharmacokinetics. Results: CCI-779 produced an objective response rate of 7{\%} (one complete response and seven partial responses) and minor responses in 26{\%} of these advanced RCC patients. Median time to tumor progression was 5.8 months and median survival was 15.0 months. The most frequently occurring CCI-779-related adverse events of all grades were maculopapular rash (76{\%}), mucositis (70{\%}), asthenia (50{\%}), and nausea (43{\%}). The most frequently occurring grade 3 or 4 adverse events were hyperglycemia (17{\%}), hypophosphatemia (13{\%}), anemia (9{\%}), and hypertriglyceridemia (6{\%}). Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level. Patients were retrospectively classified into good-, intermediate-, or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa. Within each risk group, the median survivals of patients at each dose level were similar. Conclusion: In patients with advanced RCC, CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested.",
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T1 - Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma

AU - Atkins, Michael B.

AU - Hidalgo, Manuel

AU - Stadler, Walter M.

AU - Logan, Theodore

AU - Dutcher, Janice P.

AU - Hudes, Gary R.

AU - Park, Young

AU - Liou, Song Heng

AU - Marshall, Bonnie

AU - Boni, Joseph P.

AU - Dukart, Gary

AU - Sherman, Matthew L.

PY - 2004

Y1 - 2004

N2 - Purpose: To evaluate the efficacy, safety, and pharmacokinetics of multiple doses of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma (RCC). Patients and Methods: Patients (n = 111) were randomly assigned to receive 25, 75, or 250 mg CCI-779 weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, survival, and adverse events. Blood samples were collected to determine CCI-779 pharmacokinetics. Results: CCI-779 produced an objective response rate of 7% (one complete response and seven partial responses) and minor responses in 26% of these advanced RCC patients. Median time to tumor progression was 5.8 months and median survival was 15.0 months. The most frequently occurring CCI-779-related adverse events of all grades were maculopapular rash (76%), mucositis (70%), asthenia (50%), and nausea (43%). The most frequently occurring grade 3 or 4 adverse events were hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), and hypertriglyceridemia (6%). Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level. Patients were retrospectively classified into good-, intermediate-, or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa. Within each risk group, the median survivals of patients at each dose level were similar. Conclusion: In patients with advanced RCC, CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested.

AB - Purpose: To evaluate the efficacy, safety, and pharmacokinetics of multiple doses of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma (RCC). Patients and Methods: Patients (n = 111) were randomly assigned to receive 25, 75, or 250 mg CCI-779 weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, survival, and adverse events. Blood samples were collected to determine CCI-779 pharmacokinetics. Results: CCI-779 produced an objective response rate of 7% (one complete response and seven partial responses) and minor responses in 26% of these advanced RCC patients. Median time to tumor progression was 5.8 months and median survival was 15.0 months. The most frequently occurring CCI-779-related adverse events of all grades were maculopapular rash (76%), mucositis (70%), asthenia (50%), and nausea (43%). The most frequently occurring grade 3 or 4 adverse events were hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), and hypertriglyceridemia (6%). Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level. Patients were retrospectively classified into good-, intermediate-, or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa. Within each risk group, the median survivals of patients at each dose level were similar. Conclusion: In patients with advanced RCC, CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested.

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