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

NCT00333502 | Completed Phase 1

• 2 other identifiers: CRLX-001City of Hope IRB number 05127
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Cancer; Solid Tumor

Keywords

Cancer, Neoplasms, Solid Tumor, Ovarian Cancer, Lung Cancer,; Non Small Cell Lung Cancer, Pancreatic Cancer,; Breast Cancer, Colon Cancer, Endometrial Cancer,; Kidney (Renal Cell) Cancer, Melanoma, Prostate Cancer,; Skin Cancer, Thyroid Cancer,; Solid Malignancies

Outcome Measures

Primary Outcomes (1)

• To determine the safety, toxicity and maximum tolerated dose of CRLX101 when administered intravenously to subjects with advanced solid tumors.

  6 months

Study Arms (1)

CRLX101 (formerly known as IT-101)

EXPERIMENTAL

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

Interventions

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

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

Also known as: NLG207, IT-101

CRLX101 (formerly known as IT-101)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \</= 30% of the bone marrow. Any prior radiation therapy must have been administered \>/= 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.

You may not qualify if:

• 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 \</= 4 weeks prior to first dose of study drug.
• Concurrent use of G-CSF or growth factors at the time of initiation of study drug.

Sponsors & Collaborators

• NewLink Genetics Corporation: lead

Study Sites (3)

Virginia G. Piper Cancer Center

Scottsdale, Arizona, 85258, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Related Publications (3)

• 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.

  PMID: 16533788 BACKGROUND

• 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.

  PMID: 16133526 BACKGROUND

• 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.

  PMID: 15981921 BACKGROUND

MeSH Terms

Conditions

Neoplasms; Ovarian Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pancreatic Neoplasms; Breast Neoplasms; Colonic Neoplasms; Endometrial Neoplasms; Melanoma; Prostatic Neoplasms; Skin Neoplasms; Thyroid Neoplasms

Interventions

Camptothecin; 2-cyclohexylidenhydrazo-4-phenyl-thiazole; IT-101

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Uterine Neoplasms; Uterine Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Head and Neck Neoplasms; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Yun Yen, M.D., Ph.D.

  City of Hope National Medical Center

  PRINCIPAL INVESTIGATOR

• Glenn Weiss, M.D.

  Virginia G. Piper Cancer Center

  PRINCIPAL INVESTIGATOR

• Jeffrey D. Neidhart, M.D.

  San Juan Oncology Associates

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2006
• First Posted: June 5, 2006
• Study Start: May 1, 2006
• Primary Completion: November 1, 2011
• Study Completion: April 1, 2012
• Last Updated: May 28, 2020

Record last verified: 2020-05

Locations

US (3)