scholarly journals A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer

2011 ◽  
Author(s):  
Terence Friedlander
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Nordihydroguaiaretic Acid ◽  
Insulin Like Growth Factor ◽  
Receptor Inhibition ◽  
Hormone Sensitive

scholarly journals Randomized, Phase II Study of the Insulin-Like Growth Factor-1 Receptor Inhibitor IMC-A12, With or Without Cetuximab, in Patients With Cetuximab- or Panitumumab-Refractory Metastatic Colorectal Cancer

2010 ◽  
Vol 28 (27) ◽  
pp. 4240-4246 ◽  
Author(s):  
Diane Lauren Reidy ◽  
Efsevia Vakiani ◽  
Marwan G. Fakih ◽  
Muhammad Wasif Saif ◽  
Joel Randolph Hecht ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Antitumor Activity ◽  
Disease Control ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Insulin Like Growth Factor ◽  
Wild Type ◽  
Randomized Phase Ii

Purpose To evaluate the safety and efficacy of IMC-A12, a human monoclonal antibody (mAb) that blocks insulin-like growth factor receptor-1 (IGF-1R), as monotherapy or in combination with cetuximab in patients with metastatic refractory anti–epidermal growth factor receptor (EGFR) mAb colorectal cancer. Methods A randomized, phase II study was performed in which patients in arm A received IMC-A12 10 mg/kg intravenously (IV) every 2 weeks, while patients in arm B received this same dose of IMC-A12 plus cetuximab 500 mg/m2 IV every 2 weeks. Subsequently, arm C (same combination treatment as arm B) was added to include patients who had disease control on a prior anti-EGFR mAb and wild-type KRAS tumors. Archived pretreatment tumor tissue was obtained when possible for KRAS, PIK3CA, and BRAF genotyping, and immunohistochemistry was obtained for pAKT as well as IGF-1R. Results Overall, 64 patients were treated (median age, 61 years; range, 40 to 84 years): 23 patients in arm A, 21 in arm B, and 20 in arm C. No antitumor activity was seen in the 23 patients treated with IMC-A12 monotherapy. Of the 21 patients randomly assigned to IMC-A12 plus cetuximab, one patient (with KRAS wild type) achieved a partial response, with disease control lasting 6.5 months. Arm C (all patients with KRAS wild type), however, showed no additional antitumor activity. Serious adverse events thought possibly related to IMC-A12 included a grade 2 infusion-related reaction (2%; one of 64 patients), thrombocytopenia (2%; one of 64 patients), grade 3 hyperglycemia (2%; one of 64 patients), and grade 1 pyrexia (2%, one of 64 patients). Conclusion IMC-A12 alone or in combination with cetuximab was insufficient to warrant additional study in patients with colorectal cancer refractory to EGFR inhibitors.

scholarly journals NFB-08. PHASE II STUDY OF AXITINIB IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2 AND PROGRESSIVE VESTIBULAR SCHWANNOMAS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii419-iii419
Author(s):  
Sheetal Phadnis ◽  
Mari Hagiwara ◽  
Anna Yaffe ◽  
Carole Mitchell ◽  
Theodore Nicolaides ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Volumetric Response

Abstract INTRODUCTION Vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT represent clinically and/or preclinically validated molecular targets in vestibular schwannomas. We conducted a single institution, prospective, open-label, two-stage phase II study (ClinicalTrials.gov identifier NCT02129647) to estimate the response rate to axitinib, an oral multi-receptor tyrosine kinase inhibitor targeting VEGFR, PDGFR and c-KIT, in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannomas (VS). METHODS NF2 patients older than 5 years with at least one volumetrically measurable, progressive VS were eligible. The primary endpoint was to estimate the objective volumetric response rates to axitinib. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Response was assessed every 3 months with MRI using 3-D volumetric tumor analysis and audiograms. Volumetric response and progression were defined as ≥20% decrease or increase in VS volume, respectively. RESULTS Twelve eligible patients (ages: 14–56 years) were enrolled on this study. Seven of twelve patients completed 12 cycles (range: 2 to 12 cycles). We observed two imaging and three hearing responses. Best volumetric response was -53.9% after nine months on axitinib. All patients experienced drug-related toxicities, the most common adverse events were diarrhea, hematuria and skin toxicity, not exceeding grade 2 and hypertension, not exceeding grade 3. CONCLUSIONS While axitinib has modest anti-tumor activity in NF2 patients, it is more toxic and appears to be less effective compared to bevacizumab. Based on these findings, further clinical development of axitinib for this indication does not appear warranted.

scholarly journals A phase II study of the insulin-like growth factor type I receptor inhibitor IMC-A12 in patients with metastatic uveal melanoma

2020 ◽  
Vol 30 (6) ◽  
pp. 574-579
Author(s):  
Jane Mattei ◽  
Alexej Ballhausen ◽  
Roland Bassett ◽  
Michael Shephard ◽  
Chandrani Chattopadhyay ◽  
...  
Keyword(s):  
Growth Factor ◽  
Uveal Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Factor Type ◽  
Receptor Inhibitor

Phase II Study of the Antibody Drug Conjugate Trastuzumab-DM1 for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2) –Positive Breast Cancer After Prior HER2-Directed Therapy

2011 ◽  
Vol 29 (4) ◽  
pp. 398-405 ◽  
Author(s):  
Howard A. Burris ◽  
Hope S. Rugo ◽  
Svetislava J. Vukelja ◽  
Charles L. Vogel ◽  
Rachel A. Borson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Antibody Drug

Purpose The antibody-drug conjugate trastuzumab-DM1 (T-DM1) combines the biologic activity of trastuzumab with targeted delivery of a potent antimicrotubule agent, DM1, to human epidermal growth factor receptor 2 (HER2) –overexpressing cancer cells. Based on results from a phase I study that showed T-DM1 was well tolerated at the maximum-tolerated dose of 3.6 mg/kg every 3 weeks, with evidence of efficacy, in patients with HER2-positive metastatic breast cancer (MBC) who were previously treated with trastuzumab, we conducted a phase II study to further define the safety and efficacy of T-DM1 in this patient population. Patients and Methods This report describes a single-arm phase II study (TDM4258g) that assessed efficacy and safety of intravenous T-DM1 (3.6 mg/kg every 3 weeks) in patients with HER2-positive MBC who had tumor progression after prior treatment with HER2-directed therapy and who had received prior chemotherapy. Results With a follow-up of ≥ 12 months among 112 treated patients, the objective response rate by independent assessment was 25.9% (95% CI, 18.4% to 34.4%). Median duration of response was not reached as a result of insufficient events (lower limit of 95% CI, 6.2 months), and median progression-free survival time was 4.6 months (95% CI, 3.9 to 8.6 months). The response rates were higher among patients with confirmed HER2-positive tumors (immunohistochemistry 3+ or fluorescent in situ hybridization positive) by retrospective central testing (n = 74). Higher response rates were also observed in patients whose tumors expressed ≥ median HER2 levels by quantitative reverse transcriptase polymerase chain reaction for HER2 expression, compared with patients who had less than median HER2 levels. T-DM1 was well tolerated with no dose-limiting cardiotoxicity. Most adverse events (AEs) were grade 1 or 2; the most frequent grade ≥ 3 AEs were hypokalemia (8.9%), thrombocytopenia (8.0%), and fatigue (4.5%). Conclusion T-DM1 has robust single-agent activity in patients with heavily pretreated, HER2-positive MBC and is well tolerated at the recommended phase II dose.

Phase II study of the insulin-like growth factor-1 receptor (IGF-1R) antibody cixutumumab (C) in patients (pts) with thymoma (T) and thymic carcinoma (TC).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e17525-e17525 ◽  
Author(s):  
A. Rajan ◽  
A. W. Berman ◽  
R. J. Kelly ◽  
A. Lopez-Chavez ◽  
R. Dechowdhury ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Thymic Carcinoma ◽  
Phase Ii Study ◽  
Insulin Like Growth Factor

A single-arm phase II study of ADT with PD-1 blockade and docetaxel in men with metastatic hormone-sensitive prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS271-TPS271
Author(s):  
Jessica Hawley ◽  
Timothy Geoffrey Bowler ◽  
Xinzheng Victor Guo ◽  
Matthew Dallos ◽  
Emerson A. Lim ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
De Novo ◽  
Phase Ii Study ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Tumor Cell Death ◽  
Serum Samples ◽  
Open Label ◽  
Hormone Sensitive

TPS271 Background: Overall survival of men with de novo metastatic, hormone-sensitive prostate cancer (mHSPC) is improved by treatment intensification with docetaxel and hormone therapy compared to androgen deprivation therapy (ADT) alone. However, castration-resistant prostate cancer (CRPC) invariably develops. Reprogramming the immune system in the mHSPC setting is a novel approach to delay progression to CRPC. In the hormone-sensitive setting, ADT induces a robust and functional immune infiltrate into the tumor microenvironment (TME), with upregulation of immune checkpoint molecules (PD-1 and PD-L1). These effects diminish as castration resistance emerges. Docetaxel causes immunogenic tumor cell death and stimulates antigen presentation. We hypothesize that leveraging the immunogenic effects of ADT with PD-1 blockade and docetaxel will promote antitumor immune killing and improve clinical outcomes. Methods: This is an open-label, single-arm, phase II study of ADT, cemiplimab, and docetaxel in patients with de novo mHSPC (N=20). Subjects will receive continuous ADT, followed by a two-cycle lead-in of cemiplimab prior to the standard six cycles of docetaxel. Cemiplimab will be continued q3weeks for one year or until disease progression or intolerable side effect. The primary endpoint is undetectable PSA at 6 months. Secondary endpoints include time to development of CRPC and radiographic response. Subjects will be monitored for toxicity using a Bayesian adaptive study design with an early stopping rule for toxicity. Correlative studies will determine the effects of ADT and PD-1 blockade on the TME by comparing baseline and on-treatment biopsies using transcriptional data from single-cell RNA-sequencing and standard immunohistochemistry (IHC). Serum samples will also be collected to quantify the effects of therapy on circulating levels of immunosuppressive cytokines. The study is open with 3 patients currently enrolled at the time of submission. Clinical trial information: NCT03951831.

Sign in / Sign up

Export Citation Format

Share Document