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

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

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).

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: CRLX101; Other: Best Supportive Care

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
• Enrollment (Actual): 157
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Arkhangelsk Regional Clinical Oncology Center
  • Bryansk, Russian Federation, 241033
    • State Healthcare Institution: Bryansk Regional Oncology Center
  • Chelyabinsk, Russian Federation, 454087
    • Chelyabinsk Regional Clinical Oncology Center
  • Kursk, Russian Federation, 305035
    • Kursk Regional Oncology Center
  • Moscow, Russian Federation, 115478
    • Institution of the Russian Academy of Medical Sciences Russian Oncological Research Center
  • Moscow, Russian Federation, 129128
    • Non-Government Medical Institution: Central Clinical Hospital #2
  • Nizhny Novgorod, Russian Federation, 603081
    • State Healthcare Institution of Nizhny Novgorod Regiona Nizhny Novgorod Oncology Center
  • Novosibirsk, Russian Federation, 630047
    • City Clinical Hospital #1
  • Pyatigorsk, Russian Federation, 357500
    • State Medical Institution: Pyatigorsk Oncological Center
  • St. Petersburg, Russian Federation, 197022
    • St. Petersburg Medical University
  • St. Petersburg, Russian Federation, 198255
    • City Clinical Oncology Center
  • Stavropol, Russian Federation, 355047
    • Stavropol Regional Clinical Oncology Center
  • Tambov, Russian Federation, 392013
    • Tambov Regional Oncology Center
  • Vladivostok, Russian Federation, 690105
    • Primorsky Regional Oncology Center
  • Yaroslavl, Russian Federation, 150054
    • Regional Clinical Oncology Center
  • Republic Of Mordovia
    • Saransk, Republic Of Mordovia, Russian Federation, 430032
      • State Medical Institution Republican Oncology Center
  • Republic Of Tatarstan
    • Kazan, Republic Of Tatarstan, Russian Federation, 420029
      • State Medical Institution Republic Clinical Oncological Center under the Healthcare Ministry of Tatarstan Republic
• Ukraine
  • Dnipropetrovsk, Ukraine, 49102
    • Dnipropetrovsk State Medical Academy
  • Donetsk, Ukraine, 83092
    • Public Treatment and Prophylaxis Institution; Donetsk Regional Antitumor Center
  • Ivano-Frankivsk, Ukraine, 76000
    • Ivano-Frankovsk State Medical University; Oncology Department Clinical Facility
  • Kharkiv, Ukraine, 61070
    • Kharkiv State Public Healthcare Institution: Kharkiv Regional Clinical Oncology Center
  • Khmelnytsky, Ukraine, 29009
    • Khmelnytskyi Regional Oncology Center
  • Kyiv, Ukraine, 03115
    • Kyiv City Oncology Hospital
  • Sumy, Ukraine, 40005
    • Sumy Regional Clinical Oncology Center
  • Uzhgorod, Ukraine, 88011
    • Zakarpattia Regional Clinical Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CRLX101	Drug: CRLX101; CRLX101 is administered at 15mg/m2 IV every other week; Other Names: NLG207
OTHER: Best supportive care	Other: Best Supportive Care; best supportive care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Compare Overall Survival of Patients Treated With CRLX101 + BSC to Those Patients Treated With BSC Only	Comparison of survival among patients treated with CRLX101 + best supportive care vs patients treated wiht best supportive care only.	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Objective Response Rate (ORR) of CRLX101+ BSC Compared to BSC Only	Comparison of objective response rate in subjects treated with CRLX101+BSC versus subjects treated with BSC alone.	12 months

Collaborators and Investigators

• Sponsor: NewLink Genetics Corporation
• Investigators: Study Chair: NewLink Genetics, NewLink Genetics Inc

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): February 1, 2013
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: June 22, 2011
• First Submitted That Met QC Criteria: June 23, 2011
• First Posted (ESTIMATE): June 27, 2011

Study Record Updates

• Last Update Posted (ACTUAL): May 28, 2020
• Last Update Submitted That Met QC Criteria: May 26, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: CRLX-002