A Phase 2 Study of CRLX101 in Patients With Advanced Non-Small Cell Lung Cancer

Tracking Information
First Submitted Date ICMJE	June 22, 2011
First Posted Date ICMJE	June 27, 2011
Results First Submitted Date	October 26, 2015
Results First Posted Date	May 24, 2017
Last Update Posted Date	May 24, 2017
Study Start Date ICMJE	June 2011
Actual Primary Completion Date	February 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 18, 2017)	To Compare Overall Survival of Patients Treated With CRLX101 + BSC to Those Patients Treated With BSC Only [ Time Frame: Up to 18 months ]; Comparison of survival among patients treated with CRLX101 + best supportive care vs patients treated wiht best supportive care only.
Original Primary Outcome Measures ICMJE; (submitted: June 23, 2011)	To compare overall survival of patients treated with CRLX101 to those patients treated with best supportive care. [ Time Frame: Up to 18 months ]
Change History	Complete list of historical versions of study NCT01380769 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 18, 2017)	Assess Objective Response Rate (ORR) of CRLX101+ BSC Compared to BSC Only [ Time Frame: 12 months ]; Comparison of objective response rate in subjects treated with CRLX101+BSC versus subjects treated with BSC alone.
Original Secondary Outcome Measures ICMJE; (submitted: June 23, 2011)	Assess response rate of CRLX101 compared to BSC [ Time Frame: 12 months ]; Compare Changes in quality of like (as determined by a self-administered quality of life questionnaire) in patients receiving CLRX101 vs. BSC [ Time Frame: 12 months ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Phase 2 Study of CRLX101 in Patients With Advanced Non-Small Cell Lung Cancer
Official Title ICMJE	A Randomized, Phase 2, Study to Assess the Safety and Activity of CRLX101, a Nanoparticle Formulation of Camptothecin, in Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed One or Two Previous Regimens of Chemotherapy
Brief Summary	The purpose of this study is to compare median overall survival of patients with advanced non-small cell lung cancer (NSCLC) treated with CRLX101 to patients treated with best supportive care (BSC).
Detailed Description	Lung cancer remains the leading cause of cancer-related mortality in men and women worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer. The development of targeted therapies has changed the approach to treating NSCLC significantly over the past decade with targeted therapies generally possessing safety advantages over traditional cytotoxic regimens. However, combination paradigms and resistance patterns complicate the use of these agents. CRLX101 is a nanoparticle comprised of camptothecin (CPT) conjugated to a cyclodextrin-based polymer. CRLX101 is designed to increase the exposure of tumor cells to CPT while minimizing side effects.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Non-Small Cell Lung Cancer
Intervention ICMJE	Drug: CRLX101 CRLX101 is administered at 15mg/m2 IV every other week; Other: Best Supportive Care best supportive care
Study Arms	Experimental: CRLX101 Intervention: Drug: CRLX101; Best supportive care Intervention: Other: Best Supportive Care
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 2, 2015)	157
Original Estimated Enrollment ICMJE; (submitted: June 23, 2011)	148
Actual Study Completion Date	October 2014
Actual Primary Completion Date	February 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Male or female patients who are ≥ 18-years of age.; Histologically or cytologically confirmed, locally advanced or metastatic NSCLC (adenocarcinoma, bronchoalveolar, squamous cell, large cell, or mixed carcinoma) that is not amendable to surgical treatment and patient has have failed 1 or 2 different lines of chemotherapy.; Measureable disease and evidence of progression on the previous therapy. Progression may be clinical or radiological.; ECOG performance status of 0 or 1.; Life expectancy of at least 3 months.; Hemoglobin ≥ 10 g/dL.; Absolute neutrophil count (ANC) ≥ 1500 cells/µL without growth factor support.; Platelet count ≥ 100,000 cells/µL without support.; Adequate hepatic and renal function including the following: Total bilirubin < 2 × ULN, AST or ALT ≤ 2.5 × ULN or ≤ 5 × ULN for patients with liver metastasis, PTT within normal limits, INR ≤ 1.5, Serum Creatinine <1.5 ULN; At least 4 weeks post any radiotherapy or biological therapy; at least 6 weeks post nitrosoureas therapy.; Full recovery from diagnostic or therapeutic surgery (i.e., complete wound healing) and at least 30 days have elapsed prior to initial dosing.; Full recovery from the toxic effects of prior therapy (i.e., Common Toxicity Criteria [CTC] Grade 1 or less with the exception of Grade 2 alopecia).; Women of childbearing potential must have adequate pregnancy test. If postmenopausal, must be ≥ 12 months since last menses.; Women of childbearing potential and men must agree to use an effective form of contraception during the study and for 60 days after the last dose of study drug. Exclusion Criteria: CNS metastases by radiologic evidence or histology, unless clinically stable (must have been treated by resection or radiation) for at least 4 weeks prior to first dose of study drug. Patients may not be receiving dexamethasone for control of CSF pressure.; Concurrent therapeutic anticoagulation: PTT less than or equal to 1.5 × ULN or low dose aspirin and low-weight heparin only are allowed.; More than 2 previous lines of chemotherapy for lung cancer. This includes biologic (immunotherapy) therapy.; History of previous cerebrovascular accident (CVA) or history transient ischemic attack (TIA) within 6 months of study entry.; History of prior malignancy not cured by excision. Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are not excluded, but patients with other prior malignancies must have had at least 2-year disease free interval.; Recent history (within 6 months of screening) of unstable angina, myocardial infarction, or NYHA Class III or IV congestive heart failure; History of cardiac arrhythmia requiring medical or electrical therapy.; QTc > 450 msec for males and > 470 msec for females.; Any major surgery within 30 days or minor surgery within 10 days of study entry, or patient not recovered from surgery.; History of organ or bone marrow transplant.; Known active and/or uncontrolled infection, including HIV and are not stable on antiretroviral therapy.; Any investigational therapy within 28 days of study entry.; Pregnant or nursing.; Anyone who in the judgment of the investigator cannot comply with the protocol, provide truly informed consent, or is likely to live < 90 days; Severe or significant allergy to any chemotherapy or premedication.; Clinically evident ascites (e.g., abdominal distention, bulging and/or fluid wave) or Grade 3 peripheral edema.; Any prior cancer treatment with a topoisomerase I inhibitor.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Russian Federation, Ukraine
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01380769
Other Study ID Numbers ICMJE	CRLX-002
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	NewLink Genetics Corporation
Study Sponsor ICMJE	NewLink Genetics Corporation
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Chair: NewLink Genetics NewLink Genetics Inc
PRS Account	NewLink Genetics Corporation
Verification Date	April 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP