Evidence map›Paper›PMID 23397498›Full record

Trial reportInvestigational new drugs2013

First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies.

Glen J Weiss, Joseph Chao, Jeffrey D Neidhart, Ramesh K Ramanathan, Dawn Bassett, James A Neidhart, Chung Hang J Choi, Warren Chow, Vincent Chung, Stephen J Forman and 15 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Investigational new drugs, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02648711 (Evaluation of an Alternative Schedule for CRLX101 Alone in Combination With Bevacizumab and in Combination With mFOLFOX6 in Subjects With Advanced Solid Tumor Malignancies), which is not on this map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
10.6field-weighted citation impact, top 1% 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.

NCT02648711 phase1terminatednot on this mapstarted 2015, after this paper: background citation

Evaluation of an Alternative Schedule for CRLX101 Alone in Combination With Bevacizumab and in Combination With mFOLFOX6 in Subjects With Advanced Solid Tumor Malignancies

TypeinterventionalSponsorNewLink Genetics CorporationRan2015 to 2018Enrolled41ConditionsSolid TumorsArmsCRLX101, Bevacizumab, mFOLFOX6
3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 1 synthesis or guideline pooled it, 219 citations in OpenAlex.

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  18. Treatment of lung diseasesMaterials today. Bio · 2025
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25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 6 institutions in 1 country.

Glen J Weiss *Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare/TGen, Scottsdale, AZ, USA.
Joseph Chao *City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Jeffrey D NeidhartSan Juan Oncology Associates, Farmington, NM, USA.
Ramesh K RamanathanVirginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare/TGen, Scottsdale, AZ, USA.
Dawn BassettVirginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare/TGen, Scottsdale, AZ, USA.
James A NeidhartSan Juan Oncology Associates, Farmington, NM, USA.
Chung Hang J ChoiCalifornia Institute of Technology, Pasadena, CA, USA.
Warren ChowCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Vincent ChungCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Stephen J FormanCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Edward GarmeyCerulean Pharma Inc., Cambridge, MA, USA.
Jungyeon HwangCerulean Pharma Inc., Cambridge, MA, USA.
D Lynn KalinoskiCerulean Pharma Inc., Cambridge, MA, USA; Calando Pharmaceuticals, Pasadena, CA, USA.
Marianna KoczywasCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Jeffrey LongmateCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Roger J MeltonSeventh Wave, Chesterfield, MO, USA.
Robert MorganCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Jamie OliverPeptagen, Inc., Raleigh, NC, USA.
Joanna J PeterkinCerulean Pharma Inc., Cambridge, MA, USA.
John L RyanCerulean Pharma Inc., Cambridge, MA, USA.
Thomas SchluepCalando Pharmaceuticals, Pasadena, CA, USA.
Timothy W SynoldCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Przemyslaw TwardowskiCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Mark E DavisCalifornia Institute of Technology, Pasadena, CA, USA.
Yun YenCity of Hope Comprehensive Cancer Center, Duarte, CA, USA; Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
City of Hope · USCerulean Pharma (United States) · USTranslational Genomics Research Institute · USCalifornia Institute of Technology · USSan Juan Oncology Associates · USCalando Pharmaceuticals (United States) · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
QUANTITATIVE IMAGE ANALYSIS SPECIALIZED RESOURCE COREU54CA119347 · NCI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI HEATH, JAMES R. · 2005 to 2009
$17.8M
NCI NIH HHS CA U54119347NCI NIH HHS P30 CA033572NCI NIH HHS U54 CA119347
6 · The paper itself

Abstract

Patients with advanced solid malignancies were enrolled to an open-label, single-arm, dose-escalation study, in which CRLX101 was administered intravenously over 60 min among two dosing schedules, initially weekly at 6, 12, and 18 mg/m(2) and later bi-weekly at 12, 15, and 18 mg/m(2). The maximum tolerated dose (MTD) was determined at 15 mg/m(2) bi-weekly, and an expansion phase 2a study was completed. Patient samples were obtained for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Response was evaluated per RECIST criteria v1.0 every 8 weeks. Sixty-two patients (31 male; median age 63 years, range 39-79) received treatment. Bi-weekly dosing was generally well tolerated with myelosuppression being the dose-limiting toxicity. Among all phase 1/2a patients receiving the MTD (n = 44), most common grade 3/4 adverse events were neutropenia and fatigue. Evidence of systemic plasma exposure to both the polymer-conjugated and unconjugated CPT was observed in all treated patients. Mean elimination unconjugated CPT Tmax values ranged from 17.7 to 24.5 h, and maximum plasma concentrations and areas under the curve were generally proportional to dose for both polymer-conjugated and unconjugated CPT. Best overall response was stable disease in 28 patients (64 %) treated at the MTD and 16 (73 %) of a subset of NSCLC patients. Median progression-free survival (PFS) for patients treated at the MTD was 3.7 months and for the subset of NSCLC patients was 4.4 months. These combined phase 1/2a data demonstrate encouraging safety, pharmacokinetic, and efficacy results. Multinational phase 2 clinical development of CRLX101 across multiple tumor types is ongoing.

Indexed as

AdultAgedArea Under CurveBiopsyCamptothecinCelluloseCyclodextrinsDemographyDisease-Free SurvivalDose-Response Relationship, DrugFemaleHumansImmunohistochemistryMaleMaximum Tolerated DoseMiddle AgedCamptothecinCellulosecyclodextrin polymerCyclodextrinsIT-101

Identifiers

PMID23397498
PMCPMC3774600
OpenAlexW2158018814

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.