A dose escalation, safety, and tolerability study of MN-029 in patients with advanced solid tumors.

Abstract:

PURPOSE:To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and tolerability of MN-209, a novel vascular disrupting agent, in patients with advanced solid tumors. STUDY DESIGN:MN-029 was administered weekly for three consecutive weeks out of four; two cycles were planned. Dose escalation proceeded by 100% per toxicity criteria. Intra-patient dose escalation was permitted. RESULTS:Twenty patients received a total of 151 infusions of MN-029. No DLTs or grade 4 toxicities occurred. The most common adverse events were nausea, vomiting, arthralgias, and headache. One patient developed acute substernal chest pain 4 days after his first dose of MN-029 and was removed from the study. An MTD was not determined. The recommended phase II dose was identified as 180 mg/m(2)/week. One patient with advanced pancreatic cancer attained a partial response lasting 10 weeks. CONCLUSIONS:MN-029 was well tolerated in this schedule. Further development of this class of agents is warranted, especially in combination with other anti-cancer treatments.

journal_name

Invest New Drugs

authors

Traynor AM,Gordon MS,Alberti D,Mendelson DS,Munsey MS,Wilding G,Gammans RE,Read WL

doi

10.1007/s10637-009-9264-2

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

509-15

issue

4

eissn

0167-6997

issn

1573-0646

journal_volume

28

pub_type

杂志文章,多中心研究
  • Artemisinin reduces human melanoma cell migration by down-regulating alpha V beta 3 integrin and reducing metalloproteinase 2 production.

    abstract::Artemisinin and its derivatives are well known antimalarial drugs, particularly useful after resistance to traditional antimalarial pharmaceuticals has started to occur in Plasmodium falciparum. In recent years, anticancer activity of artemisinin has been reported both in vitro and in vivo. Artemisinin has inhibitory ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-008-9188-2

    authors: Buommino E,Baroni A,Canozo N,Petrazzuolo M,Nicoletti R,Vozza A,Tufano MA

    更新日期:2009-10-01 00:00:00

  • Early depth of tumor shrinkage and treatment outcomes in non-small cell lung cancer treated using Nivolumab.

    abstract::Background It would be useful to have criteria for predicting long-term treatment responses to immune checkpoint inhibitors (ICIs). Maximum depth of response correlates with treatment outcomes among patients receiving programmed death protein 1 axis inhibitors for non-small cell lung cancer (NSCLC). We investigated as...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-019-00770-y

    authors: Kawachi H,Fujimoto D,Morimoto T,Hosoya K,Sato Y,Kogo M,Nagata K,Nakagawa A,Tachikawa R,Tomii K

    更新日期:2019-12-01 00:00:00

  • TRAIL shows potential cardioprotective activity.

    abstract::Recent clinical trials carried out in patients with advanced cancer have shown that recombinant TRAIL administration is usually safe and well tolerated when used either alone or in association with chemotherapeutic drugs. Notably, anticancer chemotherapy can be associated to cardiomiopathy. We have here demonstrated t...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9627-8

    authors: Toffoli B,Bernardi S,Candido R,Zacchigna S,Fabris B,Secchiero P

    更新日期:2012-06-01 00:00:00

  • Pharmacokinetics and metabolism of the staurosporine analogue CGP 41 251 in mice.

    abstract::Studies with CGP 41 251 (I), an N-benzoylstaurosporine derivative and PKC-alpha inhibitor, revealed that oral administration of 400 microg/day of the compound to wild type mice on four successive days reversed multi drug resistance (Killion et al. Oncology Research 7: 453-459, 1995). In our study, the same regimen of ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1023/a:1006260217400

    authors: van Gijn R,van Tellingen O,Haverkate E,Kettenes-van den Bosch JJ,Bult A,Beijnen JH

    更新日期:1999-01-01 00:00:00

  • Pharmacokinetics of 5,6-dihydro-5-azacytidine (NSC-264880) in the foxhound.

    abstract::An HPLC analytical method was applied to the determination of plasma concentrations of 5,6-dihydro-5-azacytidine (NSC 264880, DHAC) in two foxhounds after a rapid intravenous infusion of 300 mg/kg DHAC. The dose employed is the mouse equivalent LD10 dose which results in mild reversible toxicity in the dog. The declin...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00180191

    authors: Malspeis L,Cheng H,Staubus AE

    更新日期:1983-01-01 00:00:00

  • Distribution, elimination, metabolism and bioavailability of hexamethylenebisacetamide in rats.

    abstract::Hexamethylenebisacetamide (HMBA), an in vitro differentiating agent, was studied for its pharmacodynamic actions in animals. Plasma stability, organ distribution, excretion, oral bioavailability, and estimates of pharmacokinetic parameters and acute lethality were determined in rats. The single dose intraperitoneal LD...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00179430

    authors: Litterst CL,Roth JS,Kelley JA

    更新日期:1985-01-01 00:00:00

  • Effect of morin on tissue lipid peroxidation and antioxidant status in 1, 2-dimethylhydrazine induced experimental colon carcinogenesis.

    abstract::Colon cancer is the third most malignant neoplasm in the world and it remains today an important cause of death, especially in western countries. In this study, we have evaluated the chemopreventive efficacy of morin on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in 1,2-dimethylhydra...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-008-9136-1

    authors: Sreedharan V,Venkatachalam KK,Namasivayam N

    更新日期:2009-02-01 00:00:00

  • Activity of the polyamine-vectorized anti-cancer drug F14512 against pediatric glioma and neuroblastoma cell lines.

    abstract::The poor prognosis of children with high-grade glioma (HGG) and high-risk neuroblastoma, despite multidisciplinary therapeutic approaches, demands new treatments for these indications. F14512 is a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells via the Polyamine...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-014-0132-3

    authors: Leblond P,Boulet E,Bal-Mahieu C,Pillon A,Kruczynski A,Guilbaud N,Bailly C,Sarrazin T,Lartigau E,Lansiaux A,Meignan S

    更新日期:2014-10-01 00:00:00

  • Cytotoxicity of anthraquinones from the roots of Pentas schimperi towards multi-factorial drug-resistant cancer cells.

    abstract:INTRODUCTION:Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal (1), damnacanthol (2), 3-hydroxy-2-hydroxymethyl anthraquinone (3) and schimperiquinone B (4) against nine drug-s...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-015-0268-9

    authors: Kuete V,Donfack AR,Mbaveng AT,Zeino M,Tane P,Efferth T

    更新日期:2015-08-01 00:00:00

  • A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors.

    abstract::Purpose Preclinical evidence suggests dichloroacetate (DCA) can reverse the Warburg effect and inhibit growth in cancer models. This phase 1 study was undertaken to assess the safety, recommended phase 2 dose (RP2D), and pharmacokinetic (PK) profile of oral DCA in patients with advanced solid tumors. Patients and Meth...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-015-0221-y

    authors: Chu QS,Sangha R,Spratlin J,Vos LJ,Mackey JR,McEwan AJ,Venner P,Michelakis ED

    更新日期:2015-06-01 00:00:00

  • Mitoxantrone in combination with prednimustine in treatment of unfavorable non-Hodgkin lymphoma.

    abstract::Mitoxantrone (Novantrone) and prednimustine (Sterecyt) are both active as single agents in the treatment of unfavorable non-Hodgkin lymphoma (UNHL). The efficacy and toxicity of the combination of these agents (NOSTE) was evaluated in 28 patients with advanced histopathologically proven UNHL who were not eligible for ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00195368

    authors: Landys KE

    更新日期:1988-06-01 00:00:00

  • Two-stage model-based clinical trial design to optimize phase I development of novel anticancer agents.

    abstract:BACKGROUND:The phase I program of anticancer agents usually consists of multiple dose escalation studies to select a safe dose for various administration schedules. We hypothesized that pharmacokinetic and pharmacodynamic (PK-PD) modeling of an initial phase I study (stage 1) can be used for selection of an optimal sta...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-008-9216-2

    authors: Zandvliet AS,Karlsson MO,Schellens JH,Copalu W,Beijnen JH,Huitema AD

    更新日期:2010-02-01 00:00:00

  • Dual modulation of JNK and Akt signaling pathways by chaetoglobosin K in human lung carcinoma and ras-transformed epithelial cells.

    abstract::Chaetoglobosin K (ChK) is a natural product that inhibits anchorage-dependent and anchorage-independent growth of ras-transformed cells, prevents tumor-promoter disruption of cell-cell communication, and reduces Akt activation in tumorigenic cells. This study demonstrates how ChK modulates the JNK pathway in ras-trans...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9883-x

    authors: Ali A,Sidorova TS,Matesic DF

    更新日期:2013-06-01 00:00:00

  • Effect of alisertib, an investigational aurora a kinase inhibitor on the QTc interval in patients with advanced malignancies.

    abstract::Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-017-0498-0

    authors: Zhou X,Nemunaitis J,Pant S,Bauer TM,Patel M,Sarantopoulos J,Craig Lockhart A,Goodman D,Huebner D,Mould DR,Venkatakrishnan K

    更新日期:2018-04-01 00:00:00

  • Phase II study of flutamide as second line chemotherapy in patients with advanced pancreatic cancer.

    abstract::Androgen receptors are present in both pancreatic cancer tissue and cell lines. Flutamide is a potent antiandrogen widely used in clinical practice for patients with metastatic prostate cancer. This Phase II trial was undertaken to evaluate the impact of flutamide in patients with advanced pancreatic adenocarcinoma wh...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1005989519350

    authors: Sharma JJ,Razvillas B,Stephens CD,Hilsenbeck SG,Sharma A,Rothenberg ML

    更新日期:1997-01-01 00:00:00

  • Inhibition of cell growth, induction of apoptosis and mechanism of action of the novel platinum compound cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]-chloride platinum (II) monohydrochloride monohydrate.

    abstract::Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]-chloride platinum (II) monohydrochloride monohydrate (DPR) is a new platinum triamine complex obtained from the synthesis of cisplatin and procaine. In this paper we analyzed, adopting a disease-oriented strategy, the tumour selectivity of this compound...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1023/b:drug.0000006170.38419.c9

    authors: Mariggiò MA,Cafaggi S,Ottone M,Parodi B,Vannozzi MO,Mandys V,Viale M

    更新日期:2004-01-01 00:00:00

  • The notorious "drug lag" for oncology drugs in Japan.

    abstract::This study aimed to analyze the oncology "drug lag" (i.e., the delay in time required for the approval of oncology drugs) in Japan compared with that in the United States of America (US) or the European Union (EU) and to identify the factors associated with this lag. Using publicly available information, we collected ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-011-9638-0

    authors: Yonemori K,Hirakawa A,Ando M,Hirata T,Yunokawa M,Shimizu C,Katsumata N,Tamura K,Fujiwara Y

    更新日期:2011-08-01 00:00:00

  • Clinical pharmacokinetic/pharmacodynamic and physiologically based pharmacokinetic modeling in new drug development: the capecitabine experience.

    abstract::Preclinical studies, along with Phase I, II, and III clinical trials demonstrate the pharmacokinetics, pharmacodynamics, safety and efficacy of a new drug under well controlled circumstances in relatively homogeneous populations. However, these types of studies generally do not answer important questions about variabi...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审

    doi:10.1023/a:1023525513696

    authors: Blesch KS,Gieschke R,Tsukamoto Y,Reigner BG,Burger HU,Steimer JL

    更新日期:2003-05-01 00:00:00

  • Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways.

    abstract::Withaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we identified several key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA was f...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9888-5

    authors: Grogan PT,Sleder KD,Samadi AK,Zhang H,Timmermann BN,Cohen MS

    更新日期:2013-06-01 00:00:00

  • Antiangiogenic and antitumor activity of LP-261, a novel oral tubulin binding agent, alone and in combination with bevacizumab.

    abstract::LP-261 is a novel tubulin targeting anticancer agent that binds at the colchicine site on tubulin, inducing G2/M arrest. Screening in the NCI60 cancer cell lines resulted in a mean GI50 of approximately 100 nM. Here, we report the results of testing in multiple mouse xenograft models and angiogenesis assays, along wit...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9520-5

    authors: Gardner ER,Kelly M,Springman E,Lee KJ,Li H,Moore W,Figg WD

    更新日期:2012-02-01 00:00:00

  • Nafazatrom: clonogenic in-vitro assessment of activity against human malignancies.

    abstract::Nafazatrom was tested against a variety of human malignancies with the human tumor stem cell assay at one or more of the following concentrations: 1, 10, 25, and 100 micrograms/ml X 1 h or 0.05, 0.5, or 5 micrograms/ml by continuous exposure. Major (greater than or equal to 70%) inhibition was noted in 7/52 adenocarci...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00173781

    authors: Haas CD,Kyle GW,Crissman JD,Schaldenbrand MF

    更新日期:1984-01-01 00:00:00

  • Effects of the tumor vasculature targeting agent NGR-TNF on the tumor microenvironment in murine lymphomas.

    abstract::TNF-alpha may improve drug delivery to tumors by alteration of vascular permeability. However, toxicity precludes its systemic administration in patients. NGR-TNF comprises TNF coupled to the peptide CNGRC, which is a ligand for CD13. CD13 is expressed on tumor vasculature. Therefore, to assess the efficacy of NGR-TNF...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-005-4540-2

    authors: van Laarhoven HW,Gambarota G,Heerschap A,Lok J,Verhagen I,Corti A,Toma S,Gallo Stampino C,van der Kogel A,Punt CJ

    更新日期:2006-01-01 00:00:00

  • Phase II trial of intravenous melphalan in advanced colorectal carcinoma.

    abstract:BACKGROUND:Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00874443

    authors: Moore DF Jr,Pazdur R,Abbruzzese JL

    更新日期:1994-01-01 00:00:00

  • Aberrant crypt foci and AgNORs as putative biomarkers to evaluate the chemopreventive efficacy of pronyl-lysine in rat colon carcinogenesis.

    abstract::Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of potential chemopreventive agents. Our aim was to study the chemopreventive efficacy of pronyl-ly...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-008-9122-7

    authors: Panneer Selvam J,Aranganathan S,Nalini N

    更新日期:2008-12-01 00:00:00

  • Phase I study of matuzumab in combination with 5-fluorouracil, leucovorin and cisplatin (PLF) in patients with advanced gastric and esophagogastric adenocarcinomas.

    abstract:BACKGROUND:To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanc...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9848-0

    authors: Trarbach T,Przyborek M,Schleucher N,Heeger S,Lüpfert C,Vanhoefer U

    更新日期:2013-06-01 00:00:00

  • Developmental antiangiogenic agents for the treatment of non-small cell lung cancer (NSCLC).

    abstract::Standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) has primarily consisted of traditional cytotoxic chemotherapy, although use of targeted therapies has been approved in specific settings. Antiangiogenic agents represent a promising therapeutic strategy for treatment of advanced NSCLC. Beva...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审

    doi:10.1007/s10637-011-9750-1

    authors: Blumenschein GR Jr

    更新日期:2012-08-01 00:00:00

  • The effects of the anti-tumor agent mezerein on the cytotoxic capacity and oxidative metabolism of human blood cells.

    abstract::Mezerein, the most active antitumor compound isolated from the daphne species of plants, has a structural similarity to phorbol myristate acetate (PMA), the major active compound isolated from croton oil. PMA is known to have tumor promoting activity and is a potent inflammatory agent. Mezerein has similarly been repo...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00170855

    authors: Barton K,Randall G,Sagone AL Jr

    更新日期:1989-07-01 00:00:00

  • Prolonged infusion of gemcitabine in advanced solid tumors: a phase-I-study.

    abstract:BACKGROUND:Gemcitabine is a pro-drug that has to be phosphorylated to gemcitabine-triphosphate in order to exhibit its antineoplastic activity. This reaction involves the enzyme deoxycytidine kinase which is saturated at plasma concentrations following standard 30-min infusions. Pharmacological studies indicate that pr...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/s10637-005-5859-4

    authors: Schmid P,Schweigert M,Beinert T,Flath B,Sezer O,Possinger K

    更新日期:2005-03-01 00:00:00

  • Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

    abstract::Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib tre...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-015-0284-9

    authors: Yamamoto Y,Okamoto I,Otsubo K,Iwama E,Hamada N,Harada T,Takayama K,Nakanishi Y

    更新日期:2015-10-01 00:00:00

  • Posterior reversible encephalopathy syndrome induced by enzalutamide in a patient with castration-resistant prostate cancer.

    abstract::Posterior reversible encephalopathy syndrome (PRES) is a clinical/radiological syndrome characterized by symptoms that can include seizure, headache, impaired vision and hypertension, and can be confirmed by magnetic resonance imaging. Numerous reports have emerged that describe PRES in cancer patients. The list of me...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-014-0193-3

    authors: Crona DJ,Whang YE

    更新日期:2015-06-01 00:00:00