Clinical trial NCT01380769: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Lumos Pharma
Sponsor class: INDUSTRY
First posted: 2011-06-27
Enrollment: 157
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: To Compare Overall Survival of Patients Treated With CRLX101 + BSC to Those Patients Treated With BSC Only
timeFrame: Up to 18 months
Secondary outcomes:
measure: Assess Objective Response Rate (ORR) of CRLX101+ BSC Compared to BSC Only
timeFrame: 12 months
Other outcomes:
Locations:
city: Saransk
country: Russian Federation
facility: State Medical Institution Republican Oncology Center
state: Republic Of Mordovia
city: Kazan
country: Russian Federation
facility: State Medical Institution Republic Clinical Oncological Center under the Healthcare Ministry of Tatarstan Republic
state: Republic Of Tatarstan
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncology Center
city: Bryansk
country: Russian Federation
facility: State Healthcare Institution: Bryansk Regional Oncology Center
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Oncology Center
city: Kursk
country: Russian Federation
facility: Kursk Regional Oncology Center
city: Moscow
country: Russian Federation
facility: Institution of the Russian Academy of Medical Sciences Russian Oncological Research Center
city: Moscow
country: Russian Federation
facility: Non-Government Medical Institution: Central Clinical Hospital #2
city: Nizhny Novgorod
country: Russian Federation
facility: State Healthcare Institution of Nizhny Novgorod Regiona Nizhny Novgorod Oncology Center
city: Novosibirsk
country: Russian Federation
facility: City Clinical Hospital #1
city: Pyatigorsk
country: Russian Federation
facility: State Medical Institution: Pyatigorsk Oncological Center
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg Medical University
city: St. Petersburg
country: Russian Federation
facility: City Clinical Oncology Center
city: Stavropol
country: Russian Federation
facility: Stavropol Regional Clinical Oncology Center
city: Tambov
country: Russian Federation
facility: Tambov Regional Oncology Center
city: Vladivostok
country: Russian Federation
facility: Primorsky Regional Oncology Center
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Center
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk State Medical Academy
city: Donetsk
country: Ukraine
facility: Public Treatment and Prophylaxis Institution; Donetsk Regional Antitumor Center
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankovsk State Medical University; Oncology Department Clinical Facility
city: Kharkiv
country: Ukraine
facility: Kharkiv State Public Healthcare Institution: Kharkiv Regional Clinical Oncology Center
city: Khmelnytsky
country: Ukraine
facility: Khmelnytskyi Regional Oncology Center
city: Kyiv
country: Ukraine
facility: Kyiv City Oncology Hospital
city: Sumy
country: Ukraine
facility: Sumy Regional Clinical Oncology Center
city: Uzhgorod
country: Ukraine
facility: Zakarpattia Regional Clinical Oncology Center
Study officials:
affiliation: NewLink Genetics Inc
name: NewLink Genetics
role: STUDY_CHAIR
References: