Study Of CRLX101 (NLG207) In The Treatment Of Advanced Solid Tumors

Study Overview

Study of CRLX101 (NLG207) in the Treatment of Advanced Solid Tumors

CRLX101 is a nanopharmaceutical comprised of the chemotherapeutic camptothecin (CPT) conjugated to a linear, cyclodextrin-based polymer. CRLX101 is designed to increase the exposure of tumor cells to CPT while minimizing side effects. OBJECTIVES: • Determine the safety, toxicity, and the maximum tolerated dose (MTD) of CRLX101 when administered intravenously to subjects with advanced solid tumors.

N/A

Cancer
Solid Tumor

DRUG: Camptothecin (CPT) conjugated to a linear, cyclodextrin-based polymer

CRLX-001
City of Hope IRB number 05127

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2006-06-01	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-05-26
First Submitted that Met QC Criteria 2006-06-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-05-28
First Posted (ACTUAL) 2006-06-05	Results First Posted N/A	Last Verified 2020-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: CRLX101 (formerly known as IT-101) CRLX101 dosing per protocol dose escalation cohorts to MTD, then expansion cohort treated at MTD of CRLX101 15mg/m2	DRUG: Camptothecin (CPT) conjugated to a linear, cyclodextrin-based polymer Subjects who meet inclusion/exclusion criteria will receive CRLX101 every other week.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: CRLX101 (formerly known as IT-101)

CRLX101 dosing per protocol dose escalation cohorts to MTD, then expansion cohort treated at MTD of CRLX101 15mg/m2

DRUG: Camptothecin (CPT) conjugated to a linear, cyclodextrin-based polymer

Subjects who meet inclusion/exclusion criteria will receive CRLX101 every other week.

Primary Outcome Measures	Measure Description	Time Frame
To determine the safety, toxicity and maximum tolerated dose of CRLX101 when administered intravenously to subjects with advanced solid tumors.		6 months

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Male and female subjects >18 years of age with advanced, histologically-confirmed solid tumors refractory to standard therapy or for which no standard therapy exists and who have evidence of disease progression documented since their prior therapy.
Subjects must have measurable or evaluable disease.
Subjects must not have received prior chemotherapy or radiation for >/= 4 weeks prior to first dose of study drug.
Subjects may be entered if they have received prior radiation therapy involving /= 4 weeks prior to first dose of study drug and the subject must be recovered from the acute toxic effects of the treatment prior to study entry.
Subjects may be enrolled with a history of treated brain metastases that are clinically stable for >/= 4 weeks prior to first dose of study drug. Subjects may not be currently receiving dexamethasone.
ECOG performance status of < 2.
Life expectancy of greater than 12 weeks.
Subjects must have acceptable organ and marrow function at screening and pre-dose visits.
Electrocardiogram without evidence of clinically significant conduction abnormalities or active ischemia as determined by the investigator and an acceptable QTc interval.
The effects of CRLX101 on the developing human fetus are unknown, therefore, women of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation.
Ability to understand and the willingness to sign a written informed consent document.

Female subjects who are pregnant or nursing.
Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study drug or those who have not had adverse events return to baseline severity level or a severity level Grade 1 due to agents administered more than 4 weeks prior to first dose of study drug.
Subjects with a history of congestive heart failure (CHF) requiring medical therapy.
Subjects with serum amylase or lipase > 1.5X upper limit of normal (ULN).
Subjects with previous high dose chemotherapy with autologous stem cell rescue bone marrow transplantation.
Use of any investigational agent or drug within 4 weeks prior to first dose of study drug.
Metastatic disease to the CNS requiring treatment or radiation therapy.
Subjects with known untreated brain metastases or treated brain metastases that have not been stable >/= 4 weeks prior to first dose of study drug.
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, as determined by the investigator.
The presence of active coagulation disorder.
Subjects with marked baseline prolongation of QT/QTc interval (QTc interval >/= 470 msec for females and QTc interval >/= 450 msec for males).
Any prior treatment with a topoisomerase I inhibitor.
Any major surgery
Concurrent use of G-CSF or growth factors at the time of initiation of study drug.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Yun Yen, M.D., Ph.D., City of Hope National Medical Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Schluep T, Hwang J, Cheng J, Heidel JD, Bartlett DW, Hollister B, Davis ME. Preclinical efficacy of the camptothecin-polymer conjugate IT-101 in multiple cancer models. Clin Cancer Res. 2006 Mar 1;12(5):1606-14. doi: 10.1158/1078-0432.CCR-05-1566.
Schluep T, Cheng J, Khin KT, Davis ME. Pharmacokinetics and biodistribution of the camptothecin-polymer conjugate IT-101 in rats and tumor-bearing mice. Cancer Chemother Pharmacol. 2006 May;57(5):654-62. doi: 10.1007/s00280-005-0091-7. Epub 2005 Aug 26.
Cheng J, Khin KT, Davis ME. Antitumor activity of beta-cyclodextrin polymer-camptothecin conjugates. Mol Pharm. 2004 May-Jun;1(3):183-93. doi: 10.1021/mp049966y.

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