A Phase 2 Study of CRLX101(NLG207) in Patients With Advanced Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT01380769
• Recruitment Status: Completed
• First Posted: June 27, 2011
• Results First Posted: May 24, 2017
• Last Update Posted: May 28, 2020
• Sponsor: NewLink Genetics Corporation
• Information provided by (Responsible Party): Lumos Pharma ( NewLink Genetics Corporation )

Tracking Information

• First Submitted Date: June 22, 2011
• First Posted Date: June 27, 2011
• Results First Submitted Date: October 26, 2015
• Results First Posted Date: May 24, 2017
• Last Update Posted Date: May 28, 2020
• Study Start Date: June 2011
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2 Study of CRLX101(NLG207) in Patients With Advanced Non-Small Cell Lung Cancer
• Official Title: 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: CRLX101
  CRLX101 is administered at 15mg/m2 IV every other week
  Other Name: NLG207
• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 2, 2015): 157
• Original Estimated Enrollment (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

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, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Russian Federation, Ukraine

Administrative Information

• NCT Number: NCT01380769
• Other Study ID Numbers: CRLX-002
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Lumos Pharma ( NewLink Genetics Corporation )
• Study Sponsor: NewLink Genetics Corporation
• Collaborators: Not Provided

Investigators

• Study Chair: NewLink Genetics; NewLink Genetics Inc

• PRS Account: Lumos Pharma
• Verification Date: May 2020