Evidence map›Paper›PMID 25832466›Full record

Trial reportCancer2015

Targeting the interleukin-11 receptor α in metastatic prostate cancer: A first-in-man study.

Renata Pasqualini, Randall E Millikan, Dawn R Christianson, Marina Cardó-Vila, Wouter H P Driessen, Ricardo J Giordano, Amin Hajitou, Anh G Hoang, Sijin Wen, Kirstin F Barnhart and 10 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00872157 (A Limited, First-in-Man, Phase IB Evaluation of BMTP-11 in Patients With Castrate-Resistant Prostate Cancer With High-Volume Osseous Metastases and no Standard Treatment Options), which is not on this map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
6.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00872157 phase1completednot on this map

A Limited, First-in-Man, Phase IB Evaluation of BMTP-11 in Patients With Castrate-Resistant Prostate Cancer With High-Volume Osseous Metastases and no Standard Treatment Options

TypeinterventionalSponsorM.D. Anderson Cancer CenterRan2009Enrolled10ConditionsProstate CancerArmsBMTP-11
3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
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  10. Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands.Proceedings of the National Academy of Sciences of the United States of America · 2023
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  18. A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina.Proceedings of the National Academy of Sciences of the United States of America · 2019
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 2 institutions in 1 country.

Renata PasqualiniDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Randall E MillikanDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Dawn R ChristiansonDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Marina Cardó-VilaDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Wouter H P DriessenDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Ricardo J GiordanoDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Amin HajitouDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Anh G HoangDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sijin WenDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Kirstin F BarnhartDepartment of Veterinary Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Wallace B BazeDepartment of Veterinary Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Valerie D MarcottDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
David H HawkeDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Kim-Anh DoDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Nora M NavoneDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Eleni EfstathiouDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Patricia TroncosoDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Roy R LobbAlvos Therapeutics, Arrowhead Research Corporation, Pasadena, California.
Christopher J LogothetisDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Wadih ArapDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, Texas.
The University of Texas MD Anderson Cancer Center · USArrowhead Pharmaceuticals (United States) · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
West Virginia IDEA-CTRU54GM104942 · NIGMS · WEST VIRGINIA UNIVERSITY · PI JUDITH FEINBERG · 2012 to 2026
$81.0M
Targeting Tumor Microenvironment-Induced Therapy Resistance in Prostate Cancer Bone MetastasisP50CA140388 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LOGOTHETIS, CHRISTOPHER J., THOMPSON, TIMOTHY CHARLES · 2009 to 2022
$23.4M
University of Texas SPORE in Prostate CancerP50CA090270 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LOGOTHETIS, CHRISTOPHER J. · 2001 to 2007
$13.6M
Imaging Tumor Blood Vessels in Bone Metastases from Breast CancerR01DK067683 · NIDDK · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ARAP, WADIH · 2003 to 2006
$1.3M
Orbitrap Elite High-Resolution Mass Spectrometer for Proteomics and MetabolomicsS10OD012304 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HAWKE, DAVID H · 2013 to 2013
$877k
NCI NIH HHS CA140388NCI NIH HHS P50 CA090270NCI NIH HHS P50 CA140388NIDDK NIH HHS R01 DK067683NIGMS NIH HHS U54 GM104942NIH HHS S10 OD012304
6 · The paper itself

Abstract

backgroundReceptors in tumor blood vessels are attractive targets for ligand-directed drug discovery and development. The authors have worked systematically to map human endothelial receptors ("vascular zip codes") within tumors through direct peptide library selection in cancer patients. Previously, they selected a ligand-binding motif to the interleukin-11 receptor alpha (IL-11Rα) in the human vasculature.

methodsThe authors generated a ligand-directed, peptidomimetic drug (bone metastasis-targeting peptidomimetic-11 [BMTP-11]) for IL-11Rα-based human tumor vascular targeting. Preclinical studies (efficacy/toxicity) included evaluating BMTP-11 in prostate cancer xenograft models, drug localization, targeted apoptotic effects, pharmacokinetic/pharmacodynamic analyses, and dose-range determination, including formal (good laboratory practice) toxicity across rodent and nonhuman primate species. The initial BMTP-11 clinical development also is reported based on a single-institution, open-label, first-in-class, first-in-man trial (National Clinical Trials number NCT00872157) in patients with metastatic, castrate-resistant prostate cancer.

resultsBMTP-11 was preclinically promising and, thus, was chosen for clinical development in patients. Limited numbers of patients who had castrate-resistant prostate cancer with osteoblastic bone metastases were enrolled into a phase 0 trial with biology-driven endpoints. The authors demonstrated biopsy-verified localization of BMTP-11 to tumors in the bone marrow and drug-induced apoptosis in all patients. Moreover, the maximum tolerated dose was identified on a weekly schedule (20-30 mg/m(2) ). Finally, a renal dose-limiting toxicity was determined, namely, dose-dependent, reversible nephrotoxicity with proteinuria and casts involving increased serum creatinine.

conclusionsThese biologic endpoints establish BMTP-11 as a targeted drug candidate in metastatic, castrate-resistant prostate cancer. Within a larger discovery context, the current findings indicate that functional tumor vascular ligand-receptor targeting systems may be identified through direct combinatorial selection of peptide libraries in cancer patients.

Indexed as

AgedAged, 80 and overAntineoplastic AgentsBone NeoplasmsDrug Administration ScheduleHumansInterleukin-11 Receptor alpha SubunitKidneyMaleMaximum Tolerated DoseMiddle AgedPeptidesProstatic Neoplasms, Castration-ResistantProteinuriaTreatment OutcomeAntineoplastic Agentsbone metastasis-targeting peptidomimetic-11IL11RA protein, humanInterleukin-11 Receptor alpha SubunitPeptidesbone metastasis-targeting peptidomimetic-11clinical trialinterleukin-11 receptor αprostate cancervascular targeting

Identifiers

PMID25832466
PMCPMC4490036
OpenAlexW1520921451

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.