Phase II study of cixutumumab (IMC-A12, NSC742460; C) in hepatocellular carcinoma (HCC).

Abou-Alfa, G. K.; Gansukh, Bolorsukh; Chou, Jung-Mao; Shia, Jinru; Capanu, Marinela; Kälin, Moritz; Chen, H. X.; Zojwalla, Naseem; Katz, Sarah–Fee; Reidy, Diane Lauren; Dp, Kelsen; Saltz, Leonard B.

doi:10.1200/jco.2011.29.15_suppl.4043

Cited by 19 publications

(18 citation statements)

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“…17,19,20 Similar AEs were reported with an alternate IGF-1R monoclonal antibody figitumumab (Pfizer; La Jolla, CA); however, additional AEs such as increased rates of dehydration, infection, and cardiovascular toxicity were observed when figitumumab was combined with chemotherapy compared with chemotherapy alone. 21 In our single-arm study, the combination had a relatively high level of EGFR-related side effects including acneiform rash and diarrhea and a significant association with grades 3 and 4 fatigue (Table 2).…”

Section: Discussionmentioning

confidence: 78%

A Phase I/II Study of Erlotinib in Combination with the Anti-Insulin-Like Growth Factor-1 Receptor Monoclonal Antibody IMC-A12 (Cixutumumab) in Patients with Advanced Non-small Cell Lung Cancer

Weickhardt

Doebele

Oton

et al. 2012

Journal of Thoracic Oncology

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Introduction This phase I/II study evaluated the safety and anti-tumor effect of the combination of erlotinib with cixutumumab, a recombinant fully humanized anti-insulin-like growth factor-1 receptor IgG1 monoclonal antibody, in advanced non-small cell lung cancer (NSCLC). Methods Patients with advanced NSCLC were treated in an initial safety-lead and drop-down cohorts using erlotinib 150 mg/d with cixutumumab 6 or 5 mg/kg on days 1, 8, 15, and 22 in 28-day cycles (cohorts 1 and 2). Emerging pharmacokinetic data led to an additional cohort (3 + 3 design) with cixutumumab at 15 mg/kg on day 1 in 21-day cycles (cohort 3). Results Eighteen patients entered the study (6 at 6 mg/kg, 8 at 5 mg/kg, and 4 at 15 mg/kg), with median age of 65 years. Four of six patients at 6 mg/kg experienced dose-limiting toxicities (DLTs), whereas at 5 mg/kg, one of eight patients experienced DLT but three of eight patients still required a dose delay during cycle 1. At 15 mg/kg every 21 days, two of four patients experienced DLTs. In all cohorts, DLTs were either G3 rash or fatigue. Five patients had stable disease as best response and 14 patients had progressive disease. The median progression-free survival was 39 days (range 21–432+ days). Biomarkers analyses showed a trend toward better progression-free survival seen with higher free baseline insulin-like growth factor-1 levels as seen with other insulin-like growth factor-1R inhibitors. Conclusions The combinations of cixutumumab at 6 mg/kg every 7 days and 15 mg/kg every 21 days and full-dose erlotinib are not tolerable in unselected patients with NSCLC, as measured by DLT. Cixutumumab at 5 mg/kg every 7 days was tolerable per DLT, but dose delays were common. Efficacy in unselected patients with NSCLC seems to be low.

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Section: Discussionmentioning

confidence: 78%

A Phase I/II Study of Erlotinib in Combination with the Anti-Insulin-Like Growth Factor-1 Receptor Monoclonal Antibody IMC-A12 (Cixutumumab) in Patients with Advanced Non-small Cell Lung Cancer

Weickhardt

Doebele

Oton

et al. 2012

Journal of Thoracic Oncology

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“…A sarcoma study suggests activity in liposarcomas with 1 PR and 21 stable diseases in 37 patients [94]. It had no effect in hepatocellular carcinoma [95]. Small molecule inhibitors are in phase I/II studies.…”

Section: Clinical Trialsmentioning

confidence: 98%

Metabolic Syndrome and Cancer: From Bedside to Bench and Back

Extermann

2013

Cancer and Aging

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As older patients present with an average of three comorbidities beside their cancer, geriatric oncology can provide unique clues to translational research in aging and cancer. We illustrate this approach with the example of the metabolic syndrome and cancer. Epidemiologic and clinical cohorts highlighted an association between the metabolic syndrome and a higher risk and worse prognosis of various cancers. In a bedside-to-bench transition, this led to an interest in analyzing the potential mechanisms underlying this association. At least ten potential mechanisms could be implicated, with the challenge of understanding which are the dominant ones in human patients. Bench-to-bedside studies are beginning to shed some light on that aspect, and some therapeutic trials are beginning to exploit the lessons learned.

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“…In this Asiatic study, lapatinib has been evaluated in combination with paclitaxel versus paclitaxel alone in pretreated HER2 amplified aGCs. OS improvement was not statistically significant in the intention-to-treat population (11.0 vs 8.9 months; HR: 0.84; p = 0.2088) Sorafenib [53] VEGFR Tivozanib [54] Gastric cancer HER2 Lapatinib [66,67] EGFR Erlotinib [61,62] Gefitinib c-MET Foretinib [86] Rilotumumab [87,93] Onartuzumab [88] Hepatocellular carcinoma VEGFR, BRAF, KIT, RET, PDGFR Sunitinib Linifanib [55,56] FGFR Brivanib [57,58] EGFR Erlotinib [59] mTOR Temsirolimus [60] c-MET Foretinib [82] Tivantinib [83] Cabozantinib [84] MEK Selumetinib [89,90] IGF/IGFR Cixutumumab [91] The role of targeted therapy for GI tumors Review informahealthcare.com while in the Chinese subgroup of HER2-positive patients, this improvement was higher [67]. In many Phase II trials, the association of cetuximab with chemotherapy has been shown to have some efficacy [68,69] and based on the increase of RR in previous studies, Richards et al evaluated in a Phase II trial the combination of cetuximab and chemotherapy with docetaxel plus oxaliplatin (DOCOX) versus chemotherapy alone in patients affected with metastatic gastric and GEJ adenocarcinoma.…”

Section: The Improvement Of Previous Treatmentsmentioning

confidence: 99%

“…IGF and IGF-1R-targeted molecules have been also evaluated in monotherapy or in combination with sorafenib for patients with HCC, although their unfavorable toxicity profiles is limiting the clinical development [91,92].…”

Section: The Finding Of Further Pathways To Targetmentioning

confidence: 99%