Non-Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGCRLX101
CRLX101 is administered at 15mg/m2 IV every other week
OTHERBest Supportive Care
best supportive care
Sponsors
NewLink Genetics Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Compare Overall Survival of Patients Treated With CRLX101 + BSC to Those Patients Treated With BSC Only | Up to 18 months | Comparison of survival among patients treated with CRLX101 + best supportive care vs patients treated wiht best supportive care only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess Objective Response Rate (ORR) of CRLX101+ BSC Compared to BSC Only | 12 months | Comparison of objective response rate in subjects treated with CRLX101+BSC versus subjects treated with BSC alone. |
Countries
Russia, Ukraine
Participant flow
Recruitment details
The study was conducted from 04 Jul 2011 to 07 Oct 2014. A total of 24 medical clinics participated in the study.
Participants by arm
| Arm | Count |
|---|---|
| CRLX101 + BSC (Best Supportive Care) 15 mg/m2 CRLX101 infused IV over 60 minutes every other week + Standard therapy consisting of best supportive care (BSC), including at least blood and platelet transfusions, therapeutic radiation, and bone marrow support (granulocyte colony-stimulating factor \[G-CSF\]) as required. | 97 |
| BSC (Best Supportive Care) Alone Standard therapy consisting of best supportive care (BSC), including at least blood and platelet transfusions, therapeutic radiation, and bone marrow support (granulocyte colony-stimulating factor \[G-CSF\]) as required. | 50 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 11 |
Baseline characteristics
| Characteristic | BSC (Best Supportive Care) Alone | Total | CRLX101 + BSC (Best Supportive Care) |
|---|---|---|---|
| Age, Continuous | 60.6 Years STANDARD_DEVIATION 6.42 | 59.4 Years STANDARD_DEVIATION 7.68 | 58 Years STANDARD_DEVIATION 8.22 |
| Region of Enrollment Russian Federation | 29 participants | 85 participants | 56 participants |
| Region of Enrollment Ukraine | 21 participants | 62 participants | 41 participants |
| Sex: Female, Male Female | 17 Participants | 42 Participants | 25 Participants |
| Sex: Female, Male Male | 33 Participants | 105 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 76 / 97 | 39 / 50 |
| serious Total, serious adverse events | 12 / 97 | 5 / 50 |
Outcome results
Primary
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.
Time frame: Up to 18 months
Population: Intention-to-treat (ITT) and Patient Safety Population (PSP), includes all CRLX101 + BSC subjects who received at least 1 dose of study treatment and all randomized BSC alone subjects who attended at least 1 study visit. (Confidence interval if insufficient data to estimate NE = 99999.99)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CRLX101 | To Compare Overall Survival of Patients Treated With CRLX101 + BSC to Those Patients Treated With BSC Only | 6.3 months |
| Best Supportive Care | To Compare Overall Survival of Patients Treated With CRLX101 + BSC to Those Patients Treated With BSC Only | 11.9 months |
Secondary
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.
Time frame: 12 months
Population: Intention-To-Treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CRLX101 | Assess Objective Response Rate (ORR) of CRLX101+ BSC Compared to BSC Only | 6.2 Percentage of Participants |
| Best Supportive Care | Assess Objective Response Rate (ORR) of CRLX101+ BSC Compared to BSC Only | 2.0 Percentage of Participants |