Conditions: Lung Cancer
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 11
Healthy volunteers: no

Brief summary:
ABRAXANE, based on results from prior studies, is a promising drug in squamous cell carcinoma of the lung. This study will help to explore the combination of ABRAXANE and carboplatin more thoroughly in the subgroup of patients who had the best response in prior studies as well as determine whether there are any biomarkers which can predict for response.

Detailed description:
This is a single arm phase II study for subjects receiving first line therapy for metastatic squamous cell lung cancer. Following informed consent and eligibility check, all subjects will receive therapy with carboplatin and ABRAXANE on an outpatient basis. A total of 50 subjects will be enrolled over an enrollment period of about 24 months. Interim analyses will be conducted after the enrollment of subject 15, subject 30, and subject 45. Tissue biomarkers will be analyzed at baseline; and blood biomarkers will be analyzed at baseline, pre-dose on cycles 3 and 5, and then within 30 days of last dose of study treatment.

Arms:
arm 1: Carboplatin (AUC = 6; on Day 1) plus Abraxane (nab-paclitaxel; 100 mg/m\^2; Days 1, 8, 15) for 6 21-day cycles. Treatment was discontinued if: disease progression, unacceptable toxicity, withdrawn consent, or completion of treatment

Interventions: intervention 1: Carboplatin intervention 2: Abraxane
Intervention descriptions: intervention 1: Dosing: AUC = 6; on Day 1 intervention 2: 100 mg/m\^2; Days 1, 8, 15

Protocol document:
Prot_SAP_000.pdf: 
Protocol Number:  LCI-LUN-ABR-001 
Version -2:  November 11, 2015 
 
 
i 
 
 
PROTOCOL #: LCI-LUN-ABR-001 
 
TITLE:  A PILOT STUDY OF CARBOPLATIN WITH NAB-PACLITAXEL IN PATIENTS 
WITH ADVANCED NON-SMALL CELL LUNG CANCER OF SQUAMOUS HISTOLOGY 
 
LAY TITLE: A STUDY OF THE DRUGS CARBOPLATIN AND ABRAXANE FOR 
PATIENTS WITH LUNG CANCER 
 
Coordinating Site: 
Levine Cancer Institute-Research and Academic Headquarters 
Carolinas Medical Center 1021 
Morehead Medical Drive 
Charlotte, NC 28204 
 
Sponsor-Investigator: 
Kathryn F. Mileham, MD 
Levine Cancer Institute 
1021 Morehead Medical Drive, Suite 3200 
Charlotte, NC 28204 
Telephone: (980) 442-0400 
Email: Kathryn.Mileham@carolinashealthcare.org 
 
Co-Sponsor-Investigator: 
Edward S. Kim, MD Levine 
Cancer Institute 
1021 Morehead Medical Drive, Suite 3100 
Charlotte, NC 28204 
Telephone: (980) 442-3105 
Email: Edward.Kim@carolinashealthcare.org 
 
Statistician:  
                       James Symanowski, PhD 
                                          Levine Cancer Institute 
                                  1100 Blythe Blvd, Office # 1164 
Charlotte, NC 28204 
Telephone: (980) 442-2371 
Email:  James.Symanowski@carolinashealthcare.org 
 
Tissue Procurement: 
Carol Farhangfar, PhD, MBA 
Levine Cancer Institute 
1021 Morehead Medical Drive, Suite 2200 
Charlotte, NC 28204 
Telephone: (980) 442-3227 
Email: Carol.Farhangfar@carolinashealthcare.org 
 
 
 


Protocol Number:  LCI-LUN-ABR-001 
Version -2:  November 11, 2015 
 
 
ii 
 
Central Pathologist:  
James McDermott, MD 
Carolinas Pathology Group 
Carolinas Medical Center 1000 
Blythe Blvd 
Charlotte, NC 28203 
Telephone: (704) 355-2251 
Email: James.McDermott@carolinashealthcare.org 
 
Levine Cancer Institute-Roper Pathologist: 
George F. Worsham, MD 
Coastal Pathology Laboratory 
1128 Lango Avenue 
Charleston, SC 29407  
Email: 
George.Worsham@rsfh.com 
 
Levine Cancer Institute-Concord Pathologist: 
Tim Wax, MD 
CMC NorthEast Pathology Laboratory 920 
Church Street, North 
Concord, NC 28025 
Email: Tim.Wax@carolinashealthcare.org 
 
Investigator-Initiated Research Coordinator: 
Melanie Bamberg, MHA, CCRP 
Levine Cancer Institute 1021 
Morehead Medical Drive 
Charlotte, NC 28204 
Telephone: (980) 442-2366 
Email: Melanie.Bamberg@carolinashealthcare.org 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol Number:  LCI-LUN-ABR-001 
Version -2:  November 11, 2015 
 
 
iii 
 
 
The study will be conducted in compliance with the protocol, ICH-GCP and any applicable 
regulatory requirements. 
 
Confidential 
The information provided in this document is strictly confidential and is intended solely for the 
guidance of the clinical investigation.  Reproduction or disclosure of this document - whether in 
part or in full - to parties not associated with the clinical investigation, or its use for any other 
purpose, without the prior written consent of the Sponsor-Investigator is not permitted. 
 
Throughout this document, symbols indicating proprietary names (, TM) are not displayed. 
Hence, the appearance of product names without these symbols does not imply that these names 
  
are not protected.  
 


Protocol Number:  LCI-LUN-ABR-001 
Version -2:  November 11, 2015 
 
 
iv 
 
 
Commercial agents: Carboplatin & Nab-Paclitaxel 
Original Phase 2 / Version 2/ November 11, 2015 
PROTOCOL SUMMARY 
A.  Study Title 
A Pilot Study of Carboplatin with Nab-Paclitaxel in Patients with 
Advanced Non-Small Cell Lung Cancer of Squamous Histology 
B.  Indication 
Stage IV non-small cell lung cancer of squamous histology 
C.  Clinical Phase 
2 
D.  Summary of 
Rationale 
ABRAXANE, based on results from prior studies, is a promising drug 
in squamous cell carcinoma of the lung.  This study will help to 
explore the combination of ABRAXANE and carboplatin more 
thoroughly in the subgroup of patients who had the best response in 
prior studies as well as determine whether there are any biomarkers 
which can predict for response. 
E.  Study 
Objectives 
The primary objective of this study is to assess the response rate of the 
combination of carboplatin with ABRAXANE in patients with 
advanced non-small cell lung cancer (NSCLC) with squamous cell 
histology. Secondary objectives are to assess the disease control rate, 
duration of response, duration of disease control, overall survival, 
progression-free survival, and the safety and toxicity profile with this 
regimen. The exploratory objective is to assess broad molecular 
profiling. 
F.  Sample 
Approximately 50 subjects 
G. Inclusion/ 
Exclusion 
• 
Stage IV NSCLC with predominantly squamous histology 
• 
Age ≥ 18 years with ECOG ≤ 1 
• 
Measurable, biopsy accessible disease 
• 
Subjects with brain metastases must be stable for at least 4 
weeks 
• 
Adequate liver, kidney, and bone marrow function 
• 
Negative serum pregnancy test if female of child-bearing 
potential 
• 
Pre-existing peripheral neuropathy < grade 2 
H. Dosage/Dosage 
Form, Route, 
and Dose 
Regimen 
Carboplatin will be dosed on day 1 and ABRAXANE will be dosed 
(dose level 0 = 100 mg/m2) on days 1, 8, and 15 of a 21 day cycle for a 
total of 6 cycles. 


Protocol Number:  LCI-LUN-ABR-001 
Version -2:  November 11, 2015 
 
 
v 
 
I. Statistical 
Analysis 
Overall response rate will be calculated as the percent of subjects who 
achieve CR or PR and the 95% confidence interval will be estimated 
using the Clopper Pearson method. Disease control rate will be analyzed 
in a similar manner.  For both overall response rate, and disease control 
rate, the correlation with baseline subject and disease characteristics, and 
biomarkers will be evaluated using logistic regression. 
Time-to-event variables will be analyzed using survival analysis 
methods.  Survival rates will be estimated using Kaplan-Meier 
techniques.  The correlation with baseline subject and disease 
characteristics, and biomarkers will be assessed using Cox multiple 
regression models. 
Correlation among biomarkers in tissue, blood and between tissue and 
blood will be assessed.  The association among various continuous and 
discrete biomarkers will be assessed first by the exploratory data analysis 
using graphical techniques such as the scatter plot matrix, box plots, and 
BLiP plot17 . Correlation among continuous biomarkers will be 
examined by Pearson or Spearman rank correlation coefficients.   The 
association on discrete biomarkers will be tested by Fisher’s exact test. 


Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
vi 
 
 
 
SCHEMA 
 
LCI-LUN-ABR-001: Pilot Study of Carboplatin with Nab-Paclitaxel in Patients with 
Advanced Non-Small Cell Lung Cancer of Squamous Histology 
 
 
 
 
 
ICF Signed 
 
 
 
Eligibility Inclusion Criteria; 
• 
Stage IV NSCLC with predominantly squamous 
histology 
• 
Age ≥ 18 years 
• 
ECOG ≤ 1 
• 
Must have measurable, biopsy accessible disease 
• 
No prior treatment for metastatic disease 
• 
Brain metastasis must be stable for at least 4 
weeks 
• 
Adequate liver, kidney and bone marrow function 
• 
Negative serum pregnancy test in patients of 
reproductive age 
• 
Less than grade 2 pre-existing peripheral 
neuropathy 
 
 
 
Carboplatin 
+ 
AUC = 6 
Day 1 
 
ABRAXANE 
100 mg/m
2 
Days 1, 8, 15
 
 
 
21 day cycle x 6 
 
 
 
Treatment will be 
discontinued if: 
disease progression, 
unacceptable 
toxicity, withdrawn 
consent or 
completion of 
treatment. 
 
 
 
End of Treatment visit 30 days after last 
dose for clinical assessment including AEs. 
Follow-up every 6 months until death or 
lost to follow-up. 


Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
vii 
 
 
ABBREVIATIONS 
 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Asparate aminotransferase 
AUC 
Area under curve 
BSA 
Body surface area 
BRR 
Best response rate 
CI 
Confidence interval 
CPT 
Cell preparation tube 
CR 
Complete response 
cCR 
Clinical complete response 
CTCAE 
Common Terminology Criteria for Adverse Events 
eCRF 
Electronic case report form 
ECOG 
Eastern Cooperative Oncology Group 
EDTA 
Ethylene diamine tetraacetic acid 
FEC 
Fluorouracil- epirubicin hydrochloride-cyclophosphamide 
FDA 
Food and Drug Administration 
GFR 
Glomerular filtration rate 
HER-2 
Human epidermal growth factor receptor 2 
IDS 
Investigational Drug Services 
IRB 
Institutional Review Board 
IV 
Intravenous 
LCI 
Levine Cancer Institute 
MTD 
Maximum tolerated dose 
NSCLC 
Non-small cell lung cancer 
ORR 
Overall response rate 
OS 
Overall survival 
PD 
Progressive disease 
PR 
Partial response 
PFS 
Progression-free survival 
PVC 
Polyvinyl chloride 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious adverse event 
SAR 
Suspected adverse reaction 
SCC 
Squamous cell cancer 
SD 
Stable disease 
SI 
Sponsor-investigator 
SOP 
Standard operating procedure 
TTP 
Time-to-progression 
UAP 
Unanticipated adverse problem 
VEGF 
Vascular endothelial growth factor 
VEGFR-2 
Vascular endothelial growth factor receptor-2


Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
viii 
 
 
TABLE OF CONTENTS 
SCHEMA ........................................................................................................................................ i 
ABBREVIATIONS ....................................................................................................................... ii 
TABLE OF CONTENTS ............................................................................................................ iii 
1. 
OBJECTIVES ....................................................................................................................1 
1.1. 
Primary Objectives ...................................................................................................1 
1.2. 
Secondary Objectives ...............................................................................................1 
1.3. 
Exploratory Objectives ............................................................................................1 
2. 
BACKGROUND ...............................................................................................................1 
2.1. 
Non-Small Cell Lung Cancer ...................................................................................1 
2.2. 
ABRAXANE ...........................................................................................................2 
2.3. 
Carboplatin ...............................................................................................................9 
2.4. 
Rationale ……………………………………………………………………….. 10 
3. 
SUBJECT SELECTION .................................................................................................10 
3.1. 
Accrual ...................................................................................................................10 
3.2. 
Inclusion Criteria..……………………………………………………………….10 
3.3. 
Exclusion Criteria ……………………………………………………………. ... 11 
4. 
INVESTIGATIONAL PLAN..........................................................................................12 
4.1. 
Overall Study Design and Plan ..............................................................................12 
4.2. 
Registration/Enrollment ……………………………………….……………….. 12 
5. 
TREATMENT PLAN ......................................................................................................12 
5.1. 
Pre-Treatment.........................................................................................................12 
5.2. 
Agent Administration .............................................................................................15 
5.3. 
Duration of Therapy ...............................................................................................15 
5.4. 
Follow-Up ……………………………………………………………………….15 
5.5. 
Off Study ……………………………………………………………………….. 16 
6. 
STUDY PROCEDURES .................................................................................................17 
6.1. 
Informed Consent ...................................................................................................17 
6.2. 
Demographics and Medical / Treatment History ...................................................17 
6.3. 
Physical Examination .............................................................................................17 


Protocol Number:  LCI-LUN-ABR-001
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ix 
 
6.4. 
Pregnancy Test .......................................................................................................17 
6.5. 
Symptoms and Toxicities .......................................................................................17 
6.6. 
Concomitant Medications ......................................................................................17 
6.7. 
Clinical Laboratory Tests .......................................................................................18 
6.8. 
Electrocardiogram ..................................................................................................18 
6.9. 
Radiology and Tumor Measurements ....................................................................18 
6.10. Tissue and Blood-based Biomarkers......................................................................18 
6.11. Subsequent Anti-cancer Therapy and Survival Status ...........................................19 
6.12. Study Calendar .......................................................................................................20 
7. 
REQUIRED EVALUATIONS ........................................................................................21 
7.1. 
Pre-Treatment Evaluations .....................................................................................21 
7.2. 
Treatment Period ....................................................................................................21 
7.3. 
End of Therapy ......................................................................................................21 
7.4. 
Follow-Up/Survival Period ....................................................................................22 
8. 
DOSING DELAYS/DOSE MODIFICATIONS ............................................................22 
8.1. 
Dose Modifications for ABRAXANE ...................................................................22 
8.2. 
Dose Modifications for Carboplatin ......................................................................26 
9. 
SAFETY DATA COLLECTION, RECORDING AND REPORTING ......................26 
9.1. 
Unanticipated Problem (UAP) Definition ..............................................................26 
9.2. 
Adverse Event (AE) Definition..............................................................................26 
9.3. 
Suspected Adverse Reaction (SAR) Definition .....................................................28 
9.4. 
“Unexpected” Definition........................................................................................28 
9.5. 
“Serious” and “Life-Threatening” Definitions ......................................................28 
9.6. 
Serious Adverse Event (SAE) Definition ..............................................................29 
9.7. 
Safety Reporting to the Sponsor (LCI) ………………………………………….31 
9.8. 
Safety Reporting to the IRB  ..................................................................................32 
9.9. 
Safety Reporting to Celgene Corporation ..............................................................32 
10. 
TREATMENT-RELATED ADVERSE EVENTS ........................................................33 
10.1. Carboplatin .............................................................................................................33 
10.2. ABRAXANE .........................................................................................................33 
10.3. Adverse Event Characteristics ...............................................................................35 
11. 
DATA SAFETY AND MONITORING PLAN .............................................................36 
11.1. Safety Monitoring ..................................................................................................36 
11.2. Data Quality Assurance .........................................................................................36 
12. 
MEASUREMENT OF EFFECT ....................................................................................37 


Protocol Number:  LCI-LUN-ABR-001
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x 
 
12.1. Antitumor Effect ....................................................................................................37 
13. 
STATISTICAL DESIGN ................................................................................................40 
13.1. Sample Size Determination ....................................................................................40 
13.2. Analysis Endpoints ................................................................................................42 
13.3. Analysis Populations ..............................................................................................43 
13.4. Analysis Plan .........................................................................................................43 
14. 
DRUG DISTRIBUTION AND DESTRUCTION .........................................................44 
14.1. Supply and Distribution .........................................................................................44 
14.2. Drug Accountability ...............................................................................................44 
15. 
STUDY COMPLETION ................................................................................................45 
16. 
RETENTION OF RECORDS ........................................................................................46 
17. 
ETHICAL AND LEGAL ISSUES………………………………………………. ....... 46 
17.1. Ethical and Legal Conduct of the Study ……………………………………….. 46 
17.2 
Confidentiality …………………………………………………………………..47 
18. 
PUBLICATION POLICY ……………………………………………………………..47 
REFERENCES .............................................................................................................................48 
APPENDICES ..............................................................................................................................50 


Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
1 
 
 
 
1. 
OBJECTIVES 
 
1.1. 
Primary Objectives 
 
The primary objective of this study is to assess the response rate of the combination of 
carboplatin with ABRAXANE in patients with advanced non- small cell lung cancer 
(NSCLC) with squamous cell histology. 
 
1.2. 
Secondary Objectives 
 
Secondary objectives are to assess the disease control rate, duration of response, 
duration of disease control, overall survival, progression-free survival, and the safety 
and toxicity profile with this regimen. 
 
1.3. 
Exploratory Objectives 
 
Exploratory objectives are to assess broad molecular profiling. 
 
2. 
BACKGROUND 
 
2.1. 
Non-Small Cell Lung Cancer 
 
Lung cancer is the most common cause of cancer death, both in the United States and 
worldwide 1.  In the United States, in the year 2012, over 226,000 new cases of lung 
cancer were projected to be diagnosed and over 160,000 to die of the disease.1   Once 
lung cancer is diagnosed, outcomes are poor, with only 15.9% of patients surviving 
five years after diagnosis (http://seer.cancer.gov/statfacts/html/lungb.html). 
 
Squamous cell carcinoma (SCC) accounts for about 30% of new cases of lung cancer 
in the United States. Until recently, patients with SCC and adenocarcinoma had very 
similar overall survival; however, more recent studies have shown improved outcomes 
for adenocarcinoma relative to SCC.2   This is potentially due to new treatment options 
for adenocarcinoma. Several drugs known to be effective in adenocarcinoma, like 
pemetrexed and bevacizumab, should not be used in SCC, secondary to increased 
toxicity or lack of efficacy. The standard front-line chemotherapy for SCC is a 
platinum-based doublet,3 frequently carboplatin combined with a taxane, but overall 
survival in clinical trials is usually less than one year.3   New treatment options for 
SCC are needed. 


2 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
 
2.2. 
ABRAXANE 
 
ABRAXANE for Injectable Suspension (also known as ABI-007, nab-paclitaxel, 
paclitaxel protein-bound particles for injectable suspension) is an albumin-bound form 
of paclitaxel with a mean particle size of approximately 130 nanometers. Paclitaxel 
exists in the particles in a non-crystalline, amorphous state. ABRAXANE is supplied as 
a white to yellow, sterile, lyophilized powder for reconstitution with 20 mL of 0.9% 
Sodium Chloride Injection, USP prior to intravenous infusion. Each single-use vial 
contains 100 mg of paclitaxel and approximately 900 mg of human albumin. Each 
milliliter (mL) of reconstituted suspension contains 5 mg paclitaxel. ABRAXANE is 
free of solvents.  The active agent in ABRAXANE is paclitaxel. 
 
2.2.1. Indication 
 
In the United States, ABRAXANE for Injectable Suspension (paclitaxel protein-bound 
particles for injectable suspension) is indicated for the treatment of breast cancer after 
failure of combination chemotherapy for metastatic disease or relapse within 6 months 
of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless 
clinically contraindicated. 
 
On October 11, 2012, the U.S. Food and Drug Administration (FDA) approved 
ABRAXANE for use in combination with carboplatin for initial treatment of patients 
with locally advanced or metastatic non-small cell lung cancer who are not candidates 
for curative surgery or radiation therapy. 
 
ABRAXANE is also indicated for the first-line treatment of patients with metastatic 
adenocarcinoma of the pancreas, in combination with gemcitabine. 
 
2.2.2. Introduction 
 
ABRAXANE is a biologically interactive albumin-bound paclitaxel combining a 
protein with a chemotherapeutic agent in the particle form. This composition provides a 
novel approach of increasing intra-tumoral concentrations of the drug by a receptor-
mediated transport process allowing transcytosis across the endothelial cell. This 
albumin-specific receptor mediated process involves the binding of albumin to a 
specific receptor (gp60) on the intraluminal endothelial cell membrane, resulting in 
activation of a protein (caveolin-1), which initiates an internalization process in the 
endothelial cell through the formation of caveolae, with transport of the intact albumin-
bound chemotherapeutic complex via these caveolae to the underlying tumor 
interstitium. A protein specifically secreted by the tumor (SPARC) binds albumin, 
allowing release of the hydrophobic drug to the tumor cell membrane18. ABRAXANE 
is the first biologically interactive nanoparticle product leveraging this gp- 60/caveolin-
1/caveolae/SPARC pathway to increase intra-tumoral concentration of the drug and 
reducing toxic effects in normal tissue. 


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Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
 
2.2.3. Preclinical Studies with ABRAXANE 
 
Preclinical studies comparing ABRAXANE to Taxol® (paclitaxel Cremophor® EL 
solvent-based, BMS) demonstrated lower toxicities, with a maximum tolerated dose 
(MTD) approximately 50% higher for ABRAXANE compared to Taxol. At equal 
doses there was less myelosuppression and improved efficacy in a xenograft tumor 
model of human mammary adenocarcinoma.  At equitoxic doses of paclitaxel, 
ABRAXANE treated groups showed more complete regressions, longer time to 
recurrence, longer doubling time, and prolonged survival. At equal dose, tumor 
paclitaxel area under the curve was 33% higher for ABRAXANE versus solvent based 
paclitaxel, indicating more effective intratumoral accumulation of ABRAXANE18. 
 
2.2.4. Clinical Studies with ABRAXANE 
 
Every-Three-Week (Q3W) Schedule in Metastatic Breast Cancer 
In a phase I study, the MTD of ABRAXANE was determined to be 300 mg/m2 by 30 
minute infusion Q3W, without premedication or G-CSF support.4 No severe 
hypersensitivity reactions occurred with ABRAXANE despite the absence of 
premedication.  Dose-limiting toxicities included sensory neuropathy, stomatitis, and 
superficial keratopathy, which occurred at a dose of 375 mg/m2. 
 
Two multicenter phase II studies have evaluated 2 dose levels of ABRAXANE (300 
mg/m2, n=63, and 175 mg/m2, n=43) in patients with metastatic breast cancer (Ibrahim 
et al 2005 and Investigator’s Brochure, respectively). The overall response rates in these 
2 phase II trials were 40% (95% CI 25-54%) for the 175 mg/m2 dose, and 48% (95% CI 
35-60%) for the 300 mg/m2 dose. Of 39 patients receiving 300 mg/m2 as first-line 
therapy for metastatic breast cancer, 64% (95% CI 49-79%) responded.  This was 
contrasted with a 45% response rate in similar patients at the lower dose level. Grade 4 
neutropenia was noted in 24% of patients at the higher dose level, occurred primarily 
during the first cycle and resolved rapidly. 
 
A Phase III trial in patients with metastatic breast cancer compared ABRAXANE 260 
mg/m2 (n=229) to Taxol 175 mg/m2 (n=225) given Q3W.5 Efficacy analyses were based 
on the ITT population. The ORR was significantly greater for ABRAXANE than for 
Taxol for all patients (33% v 19%, respectively; P = 0.001), patients who received first-
line therapy (42% v 27%, respectively; P = 0.029), patients who received second-line or 
greater therapy (27% v 13%, respectively; P = 0.006), and patients who had received 
prior anthracycline therapy in either the adjuvant/metastatic setting (34% v 18%, 
respectively; P = 0.002) or the metastatic setting only (27% v 14%, respectively; P = 
0.010). Tumor response rate was also significantly higher for ABRAXANE than for 
Taxol in patients with visceral dominant lesions (34% v 19%, respectively; P = 0.002) 
and in patients aged younger than 65 years (34% v 19%, respectively; P < 0.001). ORR 
also was greater for ABRAXANE compared with standard paclitaxel in patients with 


4 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
nonvisceral dominant lesions (34% v 19%, respectively) and in patients  65 years old 
(27% v 19%, respectively), but the results did not reach statistical significance because 
of the small number of patients in these subsets. 
 
Median time to progression (TTP) was significantly longer with ABRAXANE than 
with Taxol for all patients (23.0 v 16.9 weeks, respectively; hazard ratio [HR] = 0.75; P 
= 0.006). 
 
There was a trend for greater median survival for all patients treated with ABRAXANE 
than with Taxol (65.0 v 55.7 weeks, respectively; P = 0.374). Although no difference in 
survival was observed in first-line patients, the difference was statistically significant in 
patients who received ABRAXANE, compared to Taxol, as second-line or greater 
therapy (56.4 v 46.7 weeks, respectively; HR = 0.73; P = .024).5 
 
The incidence of hypersensitivity reactions (any grade) was low for both arms (1% for 
ABRAXANE and 2% for Taxol). No severe (grade 3 or 4) treatment-related 
hypersensitivity reactions occurred in any of the patients in the ABRAXANE group 
despite the absence of premedication. In contrast, grade 3 hypersensitivity reactions 
occurred in the Taxol group despite standard premedication (chest pain, two patients; 
allergic reaction, three patients). Per protocol, corticosteroids and antihistamines were 
not administered routinely to patients in the ABRAXANE group; however, 
premedication was administered for emesis, myalgia/arthralgia, or anorexia in 18 
patients (8%) in the ABRAXANE group in 2% of the treatment cycles, whereas 224 
patients (> 99%) in the Taxol group received premedication in 95% of the cycles. 
 
Although the patients in the ABRAXANE group received an average paclitaxel dose-
intensity 49% greater than that received by patients in the Taxol group, the incidence of 
treatment-related grade 4 neutropenia was significantly lower in the ABRAXANE 
group than in the Taxol group (9% v 22%, respectively; P < 0.001), with a higher mean 
neutrophil nadir (1.67 v 1.31x109/L, respectively; P = 0.046), suggesting that 
polyethylated castor oil may have contributed to this toxicity in patients who received 
standard (solvent-based) paclitaxel19. 
 
As expected with a higher dose of paclitaxel, treatment-related grade 3 sensory 
neuropathy occurred more frequently in the ABRAXANE arm than in the Taxol arm 
(10% v 2%, respectively; P < 0.001); however, these episodes improved with 
interruption of treatment to grade 2 or 1 in a median 22 days and were easily managed 
with treatment interruption and dose reduction. By day 28 after its first occurrence, the 
number of patients with persistent grade 3 sensory neuropathy was the same (n = 4) in 
both study arms. No episodes of motor neuropathy or grade 4 sensory neuropathy were 
reported in either group. 
 
The only clinical chemistry value that was notably different between the two treatment 
arms was higher serum glucose levels in the Taxol–treated patients, who also had a 


5 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
higher incidence of hyperglycemia reported as an AE compared with ABRAXANE–
treated patients (7% v 1% respectively; P = 0.003). 
 
Subgroup analyses revealed that the safety profiles of ABRAXANE (n=97) and Taxol (n=30) in 
patients who received the drugs as first-line therapy were similar to those in the overall study 
population. In subgroup analyses by age, the reported AEs were similar in patients < 65 years 
old and patients  65 years old in both groups. Of the patients 65 years old, the incidences 
of the following AEs were notably lower in the ABRAXANE group (n=30) than in the Taxol 
group (n=32): neutropenia (23% v 59%, respectively), leukopenia (10% v 31%, respectively), 
nausea (20% v 38%, respectively), hyperglycemia (0% v 19%, respectively), and flushing (0% v 
16%, respectively). These data indicate no additional safety concerns for ABRAXANE in 
patients 65 years old compared with younger patients. 
 
Six patients (3%) in the ABRAXANE group and eight patients (4%) in the standard 
paclitaxel group died during the study, all as a result of disease progression. No 
treatment-related deaths occurred in the ABRAXANE group; one patient (< 1%) in the 
Taxol group died of multi-organ failure, which was considered by the investigator to be 
possibly related to treatment but may also have been a result of sepsis and/or 
progressive disease. 
 
Weekly (QW) for 3 Weeks, Every 4 Weeks Schedule in Metastatic Breast Cancer 
 
Thirty-nine patients were enrolled into a Phase I study of ABRAXANE 
administered QW for 3 weeks followed by a 1 week rest in patients with advanced solid 
tumors.6  The MTDs for heavily and lightly pre-treated patients were 100 and 150 
mg/m2 respectively.  Dose limiting toxicities included grade 4 neutropenia and grade 3 
sensory neuropathy. Premedication was not required, and unexpected, non-taxane 
associated toxicities were not observed. 
 
In a Phase II trial in heavily pretreated patients with taxane-refractory metastatic breast 
cancer, objective antitumor responses occurred in 14% of women treated with 
ABRAXANE 100 mg/m2 QW schedule. ABRAXANE weekly regimen was well 
tolerated; 91% of 106 patients were treated at the full dose of 100 mg/m2 of 
ABRAXANE without dose reductions. Based on the activity and low toxicity 
documented with this schedule, the study was expanded to evaluate the efficacy and 
safety/tolerability of a higher dose of ABRAXANE 125 mg/m2 weekly regimen in 75 
additional patients. Results of this dose-finding study confirm the dose of ABRAXANE 
100 mg/m2 as the appropriate dose for further study in this patient population.7 
 
In an open-label, randomized, multicenter phase II study comparing the antitumor 
response and toxicity of two QW dosing regimens, ABRAXANE dosed Q3W, and 
Taxotere® (polysorbate solvent-based docetaxel Sanofi-Aventis] Q3W for the first-line 
treatment of metastatic breast cancer.5 A total of 300 patients were randomized to one 
of four treatment arms: (A) ABRAXANE 300 mg/m2 IV Q3W, (n=76); (B) 


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ABRAXANE 100 mg/m2  IV Day 1,8,15 every 28 days (n=76); (C) ABRAXANE 150 
mg/m2 IV Day 1,8,15 every 28 days (n=74); or (D) Taxotere 100 mg/m2 Q3W (n=74). 
The primary objective of the trial was to evaluate the antitumor activity and safety of 
three different ABRAXANE regimens to determine the optimal dose and frequency to 
be used. Secondary objectives included the comparisons of each treatment group with 
respect to efficacy and safety, specifically: ABRAXANE to Taxotere; ABRAXANE 
QW regimens to ABRAXANE Q3W regimen; and the two dose levels of QW 
ABRAXANE.  Patients received ABRAXANE as a 30-minute IV infusion without 
premedication; Taxotere was administered as a 60-minute infusion with corticosteroid 
premedication. The primary efficacy endpoint was ORR assessed every 8 weeks in all 
treatment arms by using the RECIST guidelines. The secondary efficacy endpoints 
included total response (ORR + SD >16 weeks) and PFS. Tumor response results 
underwent an evaluation by the investigators, as well as an Independent Radiology 
Review (IRR).  If a pre-set level of congruence was observed between the tumor 
responses described by the investigators and the IRR, only the tumor response assessed 
by investigators was reported. Total of 75% of all patients were post-menopausal with a 
mean age of 53.9 years at randomization. 
 
Both ORRs and total response rates were higher in all ABRAXANE arms compared to 
the Taxotere arm. The investigator-reported ORRs were 46%, 63%, 74%, and 39%, for 
arms A, B, C, and D, respectively. This difference was statistically significant for both 
QW dosing arms of ABRAXANE compared with Taxotere, (P = 0.002 for arm B v D, 
and P 
<0.001 for arm C v D). The corresponding investigator-reported total response rates 
were 72%, 83%, 91% and 69% for the four arms, respectively. This difference reached 
statistical significance for arms B and C compared to Taxotere (P = 0.009 for arm B v 
D, and p=0.005 for arm C v. D). No significant difference in ORR was noted between 
the two weekly dosing arms (arm B v C, P = 0.24). A significant increase in PFS was 
observed in the 150 mg/m2 QW arm compared to the Taxotere arm (14.6 v 7.8 months, 
respectively, P = 0.012, hazard ratio 0.57). No significant difference in PFS was found 
between the ABRAXANE 300 mg/m2 Q3W arm and Taxotere arm (A and D). 
Similarly, PFS was not significantly different between arms A and C, or arms B and D. 
 
All three ABRAXANE arms demonstrated a favorable safety profile when compared 
with the Taxotere arm. Toxicity data occurring in >25% of patients is summarized in 
Table II. The most frequent hematologic adverse event was neutropenia, with 
significantly lower rates of Grade 3/4 neutropenia in all ABRAXANE arms (Grade 4, 
5%, 5%, 9%, 75% for arms A, B, C, D, respectively).  ABRAXANE also had lower 
rates of febrile neutropenia (1%, 1%, 1%, 8% for arms A, B, C, D, respectively) and 
fatigue (Grade 3, 5%, 0%, 3%, 19% for arms A, B, C, D, respectively) compared to 
Taxotere. While the incidence of sensory neuropathy was similar in the ABRAXANE 
and Taxotere arms, the median time to improvement in patients with Grade 3 
neuropathy was shorter in all three ABRAXANE arms (22, 22, 19 and 37 days in arms 
A, B, C and D, respectively).The ABRAXANE arms demonstrated improved safety and 


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increased efficacy compared with Taxotere. All three ABRAXANE regimens produced 
lower rates of neutropenia, febrile neutropenia, and fatigue than Taxotere. 
 
Continuous Weekly (QW) Schedule in Neoadjuvant Breast Cancer 
 
The NSABP studied the administration of ABRAXANE in a neoadjuvant 
setting to patients with locally advanced breast cancer at a dose of 100 mg/m2 QW for 
12 weeks, with no break.8   Four cycles of flurouracil- epirubric hydrochloride-
cyclophosphamide (FEC) were administered sequentially based on patients’ human 
epidermal growth factor receptor (HER2) status: HER2 negative patients received FEC-
100 (F: 500 mg/m2, E: 100 mg/m2, C: 500 mg/m2 Q3 weeks) and HER2 positive 
patients received weekly trastuzumab in addition to FEC-75 (F: 500 mg/m2, E: 75 
mg/m2, C: 500 mg/m2 Q3 weeks). Weekly trastuzumab was permitted during 
ABRAXANE and FEC-75 treatment at the discretion of the investigator.   The primary 
objective of the trial was to determine the pathologic complete response rate (pCR) in 
the breast.  Secondary endpoints included pCR in breast and nodes, clinical complete 
response rate (cCR), 2-year progression free survival, and overall survival. Sixty- five 
patients were evaluable for analyses.  The therapy was well tolerated, as 63 of 65 
patients received 4 cycles of ABRAXANE with 1 to 3 of the 12 doses omitted in 4 
patients. Of the 774 planned doses of ABRAXANE, only 14 (2%) required dose 
reductions or omissions. The mean duration of ABRAXANE treatment was 12.3 weeks 
(range 9 to 14 weeks). The mean dose intensity was 94.8 mg/m2/week (range 72.5 to 
100 mg/m2/week). A total of 62 patients went on to receive at least one dose of FEC 
with 58 completing 4 cycles, which resulted in 88% of patients who were initiated on 
therapy completing all planned chemotherapy. No grade 4 or 5 adverse 
events were reported during the ABRAXANE therapy. The most frequent grade 2 toxicities 
were fatigue, nausea, sensory neuropathy, joint pain, and diarrhea. The incidences of grades 2 
and 3 sensory neuropathy were 11% and 5%, respectively. The incidences of grades 2 and 3 
neutropenia were 6% and 3%, respectively. Following 12 weeks of ABRAXANE, a cCR of 34% 
was noted. The pCR in breast was 29%, and for the HER2+ subset, the pCR was 58%. The 
authors concluded that the administration of ABRAXANE 100 mg/m2 QW x 12 was both 
effective and tolerable. 
At the time of this update, more than 20 abstracts and publications have been presented 
at major oncology conferences or published in medical journals related to ABRAXANE 
QW schedule in breast cancer, including completed and ongoing studies. 
 
In Metastatic Non-Small Cell Lung Cancer 
Phase II trials of ABRAXANE in lung cancer as monotherapy 9 and in combination 
with carboplatin10 have shown response rates as high as 39%. These studies suggested 
that the clinical outcomes were improved with weekly ABRAXANE (at 100 mg/m2) 
versus every 3 week ABRAXANE in combination with carboplatin every three 
weeks.10   A phase III trial randomized patients with NSCLC to receive either 
carboplatin/ ABRAXANE or carboplatin/paclitaxel.  Carboplatin was administered at 


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an AUC of 6 every 3 weeks, and patients received either ABRAXANE 100 mg/m2 
weekly without premedication (n=521) or paclitaxel 200 mg/m2 every three weeks with 
premedication (n=531). The primary endpoint was overall response rate, and secondary 
endpoints included progression free survival and overall survival.  The response rates 
were significantly higher in the carboplatin/ABRAXANE arm, 33% vs. 25% (p- 0.005).  
These differences were more pronounced in the subset of patients with squamous cell 
carcinoma: a 41% response rate with ABRAXANE in combination with carboplatin vs. 
24% in the paclitaxel arm. Toxicities were similar between the two arms, with higher 
rates of grade 3 neutropenia, neuropathy, myalgias, and arthralgias on the paclitaxel 
arm, and higher rates of grade 3 anemia and thrombocytopenia on the ABRAXANE 
arm.  Median progression free survival was 6.3 months in the ABRAXANE group 
versus 5.8 months in the control group (p=0.214). Median overall survival was 12.1 
months in the ABRAXANE arm versus 11.2 months in the solvent-based paclitaxel 
group (p=0.271).12   Based on this trial, ABRAXANE is FDA approved in combination 
with carboplatin for front-line treatment of patients with advanced non-small cell lung 
cancer. 
 
2.3. 
Carboplatin 
 
Carboplatin is a commonly used agent in metastatic non-small cell lung cancer.3 It is 
frequently used in combination with other chemotherapeutic agents, including 
paclitaxel,3 docetaxel,13 and gemcitabine.14   It will be dosed according to standards 
based on ABRAXANE dosing at an AUC of 6, as calculated according to institutional 
standards. 
 
2.4. 
Rationale 
 
ABRAXANE, based on results from prior studies discussed above, appears to be a 
promising drug in squamous cell carcinoma of the lung.  In a phase II trial, carboplatin 
(AUC of 6 every three weeks) combined with weekly ABRAXANE at 100 mg/m2 had 
improved response rates versus a group receiving carboplatin with every three week 
ABRAXANE (47% vs. 30%).10 Based on this data, a dosing schedule of carboplatin at 
an AUC of 6 on day 1 of a three week cycle in combination with ABRAXANE at 100 
mg/m2 on days 1, 8, and 15 was selected for further study.  In the phase III study with 
this combination, combination therapy with ABRAXANE and carboplatin produced 
higher response rates than paclitaxel and carboplatin in metastatic non-small cell lung 
cancer (33% vs. 25%, p=0.005).  The difference in response rate was even more 
dramatic for patients with squamous cell carcinoma, with 41% responding to the 
ABRAXANE/carboplatin combination, and only 24% responding to the standard 
therapy of paclitaxel/carboplatin.  Progression free and overall survival were non- 
inferior with ABRAXANE and carboplatin.12 
 
This study will help to explore this combination more thoroughly in the subgroup of 
patients who had the best response in prior studies (i.e., patients with squamous cell 


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carcinoma), as well as determine whether there are any biomarkers which can predict 
for response. 
 
3. 
SUBJECT SELECTION 
 
3.1. 
Accrual 
 
Approximately 50 subjects will be enrolled over an enrollment period of 24 months in 
order to accrue 45 evaluable subjects (Section 13.3). Interim analyses will be conducted 
after the enrollment of subject 15, and 30 evaluable subjects. 
 
3.2. 
Inclusion Criteria 
 
Subjects must meet all the following criteria: 
 
• Histologically confirmed stage IV non-small cell lung cancer with 
predominantly squamous histology. 
• No prior systemic treatment for metastatic disease.  Patients who have 
received prior adjuvant chemotherapy for early-stage lung cancer are eligible 
if at least 12 months have elapsed between the date of final chemotherapy 
administration and the date of consent. 
• Patients must have measurable disease, defined as at least one lesion that can 
be accurately measured in at least one dimension (longest diameter to be 


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recorded for non-nodal lesions and short axis for nodal lesions) as >20 mm 
with conventional techniques or as >10 mm with CT scan, MRI, or calipers by 
clinical exam.  RECIST 1.1 will be used to measure disease per Section 12. 
• Biopsy accessible disease. 
• Patients with previous radiotherapy as definitive therapy for locally advanced 
non-small cell lung cancer are eligible, as long as the recurrence is outside the 
original radiation therapy port. Definitive radiation therapy must have been 
completed >4 weeks prior to the date the informed consent is signed. 
• Age >18 years. 
• ECOG performance status <1. 
• If patient has brain metastasis, the disease must be stable (treated and/or 
asymptomatic), for at least 4 weeks prior to the first dose of study treatment. 
• Bilirubin < 1.5 mg/dL. 
• Adequate liver function: AST and ALT < 2.5x upper limit of normal, alkaline 
phosphatase < 2.5x upper limit of normal, unless bone metastasis is present 
(<5X upper limit of normal) in the absence of liver metastasis. 
• Adequate bone marrow function: Platelets >100,000 cells/mm3 (transfusion 
independent, defined as not receiving platelet transfusions within 7 days prior to 
laboratory sample). 
•  Hemoglobin > 9.0g/dL, and ANC > 1,500 cells/mm.3 
• Adequate renal function with creatinine <1.5 mg/dL is recommended. 
• Females of childbearing potential  (defined as a sexually mature woman 
who (1) has not undergone hysterectomy [the surgical removal of the 
uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or 
(2) has not been naturally postmenopausal for at least 24 consecutive 
months [i.e., has had menses at any time during the preceding 24 
consecutive months]) must:  
• Either commit to true abstinence* from heterosexual contact (which 
must be reviewed on a monthly basis), or agree to use, and be able to 
comply with, effective contraception without interruption, 28 days 
prior to starting IP therapy (including dose interruptions), and while 
on study medication or for a longer period if required by local 
regulations following the last dose of IP and   
• Negative serum or urine β-hCG pregnancy test at screening for 
patients of childbearing potential and agree to ongoing pregnancy 
testing after the end of study therapy.  This applies even if the subject 
practices true abstinence* from heterosexual contact. 
•  Sexually active males must practice true abstinence* or use an effective 
contraception method during treatment, during dose interruptions   and for  
six months after completing treatment even if he has undergone a successful 
vasectomy.Patients must have < Grade 2 pre-existing peripheral neuropathy 
(per CTCAE). 
• Ability to understand and the willingness to sign a written informed consent 


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document. 
 
*True abstinence is acceptable when this is in line with the preferred and usual 
lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception]. 
 
3.3. 
Exclusion Criteria 
 
Subjects must not meet any of the following criteria: 
 
• Received prior systemic therapy for metastatic disease. 
• Receiving any other investigational agents. 
• Known hypersensitivity to either carboplatin or ABRAXANE. 
• Uncontrolled and current illness including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 
arrhythmia, or psychiatric illness/social situations that would limit compliance with 
study requirements. 
• Pregnant or breast feeding. 
• Other active malignancies. 
• Neuropathy ≥ grade 2. 
• Subject has received limited field radiation for palliation ≤ 2 weeks prior to starting 
study treatment and/or from whom ≥ 30% of the bone marrow was irradiated. 
 
4. INVESTIGATIONAL PLAN 
 
4.1. 
Milestone Date Definitions 
 
Eligibility date: the date of the last documented criterion that confirmed subject 
eligibility. 
Enrollment date: the date of initiation of carboplatin + abraxane treatment. 
Treatment Discontinuation date: the date the investigator decided to discontinue 
subject from carboplatin + abraxane treatment. 
Off Study date: the date on which the subject is determined to have completed the 
study (see Section 5.5). 
 
4.2. 
Overall Study Design and Plan 
 
This is a single center, single arm phase II study.  Following informed consent and 
eligibility check, all subjects will receive therapy with carboplatin and 
ABRAXANE. In the first stage of this study, 15 evaluable (as defined in Section 
13.3) patients will be enrolled. All enrolled subjects will continue with study 
treatment for six cycles, or until progression (radiographic/clinical), unacceptable 
toxicity, investigator discretion, or consent withdrawal. If 3 or more responses are 


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observed in the first stage, an additional 15 evaluable subjects will be enrolled. If a 
total of 7 or more responses are observed in the second stage (of 30 total subjects), a 
final 15 evaluable subjects will be enrolled. 
 
Data from this study will be collected on electronic case report forms (eCRFs) and 
stored in the CTMS.  
 
 
4.3. 
Registration/Enrollment 
 
Subjects will be registered in the CTMS and assigned a Study ID. The Study ID 
number will begin with “LCI” and include a two digit number sequentially assigned 
to the subject. (e.g. “LCI01” will be the Study ID assigned to the first subject.) 
 
 
 
 
5. 
TREATMENT PLAN 
 
5.1. 
Pre-Treatment 
 
No protocol-related assessments may be performed prior to obtaining informed 
consent. Baseline assessments will be conducted according to the Study Calendar in 
Section 6.12 and Section 7.1. 
 
5.2. Agent Administration 
 
Treatment will be administered on an outpatient basis. Reported adverse events and 
potential risks are described in Section 10. Appropriate dose modifications are 
described in Section 8. No investigational or commercial agents or therapies other 
than those described below may be administered with the intent to treat the subject's 
malignancy. 
 
5.2.1. ABRAXANE 
 
Subjects will receive ABRAXANE intravenously at a dose of 100 mg/m2 on days 1, 
8 and 15 of a 21 day cycle. 
 
Premedication 
Subjects do not require premedication prior to ABRAXANE administration, as 
hypersensitivity reactions are rare. Corticosteroids for anti-emetic purposes may be 
used per institutional standards. 
 
Although the solubilizing agents Cremophor® EL and Tween® 80 have long been 
implicated in adverse events including hypersensitivity reactions due to their 


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detergent-like nature and known ability to induce histamine release 15, the 
administration of solvent-based taxanes (Taxol and Taxotere) requires 
premedication with corticosteroids and histamine receptor blocking agents to 
prevent the occurrence of hypersensitivity reactions. However, the hypersensitizing 
role of the taxane molecules themselves cannot be ruled out. 
 
In the unlikely event of a mild hypersensitivity reaction, premedication may be 
administered using the premedication regimen the institution typically uses for 
solvent based paclitaxel.  In the rare event of a severe hypersensitivity reaction, 
discontinue ABRAXANE. 
 
Availability 
ABRAXANE will be supplied as commercial drug according to package 
insert parameters and provided by the institutional pharmacy. 
 
Storage and Stability 
Storage: Store the vials in original cartons at 20º C to 25º C (68º F to 
77ºF). Retain in the original package to protect from bright light.   
Stability: Unopened vials of ABRAXANE are stable until the date indicated on the 
package when stored between 20ºC to 25ºC (68ºF to 77ºF), in the original package. 
Neither freezing nor refrigeration adversely affects the stability of the product. 
 
Refer to the package insert for additional information. 
 
Study Medication Administration 
ABRAXANE is injected into a vein [intravenous (I.V.) infusion] over 30 minutes.  
The use of an in-line filter is not recommended. Following administration, the 
intravenous line should be flushed with sodium chloride 9 mg/ml (0.9%) solution 
for injection to ensure complete administration of the complete dose, according to 
local practice.  
Reconstitution and use of ABRAXANE 
1. Calculate the subject’s body surface area at the beginning of each 
cycle and if the weight changes by > 10%, from baseline weight, re-
calculate the total dose (in mg) to be administered by: 
• Total Dose (mg) = BSA x (study dose mg/m2) 
 
2. Calculate the total number of vials required by: 
•  Total Number of Vials = Total Dose (mg) 
100 (mg/vial) 
Round up the number of vials to be reconstituted to the next higher 
whole number when a fractional number of vials is obtained by the 
above formula (e.g., if the total number of vials = 4.05 or 4.5, then 5 


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vials would be reconstituted). 
 
Using sterile technique, prepare the vials for reconstitution. 
 
3. Swab the rubber stoppers with alcohol. 
4. Aseptically, reconstitute each ABRAXANE vial by injecting 20 mL of 
0.9% Sodium Chloride Injection, USP. 
• Slowly inject the 20 mL of 0.9% Sodium Chloride Injection, 
USP, over a minimum of 1 minute, using the sterile syringe 
directing the solution flow onto the inside wall of the vial. 
• 
DO NOT INJECT the 0.9% Sodium Chloride Injection, 
USP solution directly onto the lyophilized cake as this will 
result in foaming. 
• 
Once the injection is complete, allow the vial to sit for a 
minimum of 5 (five) minutes to ensure proper wetting of the 
lyophilized cake/powder. 
• 
Gently swirl and/or invert the vial slowly for at least 2 
minutes until complete dissolution of any cake/powder occurs. 
Avoid generation of foam. Rapid agitation or shaking will 
result in foaming. 
• 
If foaming or clumping occurs, stand solution for at least 
15 minutes until foam subsides. 
• 
Each ml of reconstituted product will contain 5 mg of 
paclitaxel. 
5. Calculate the exact total dosing volume of 5 mg/ml suspension 
required for the subject: 
• 
Dosing volume (ml) = Total dose (mg) / 5 (mg/ml) 
6. The reconstituted suspension should be milky and homogeneous  


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without visible particulates.  If particulates or settling are visible, the 
vial should be gently inverted again to ensure complete resuspension 
prior to use.  Discard the reconstituted suspension if precipitates are 
observed. 
7. Once the exact volume of reconstituted ABRAXANE has been 
withdrawn from the vials, discard any excess solution left over in 
accordance with standard operating procedures. 
8. Further dilution is not necessary. Inject the calculated dosing volume 
of reconstituted ABRAXANE suspension into an empty sterile, 
standard PVC IV bag using an injection port.  Inject perpendicularly 
into the center of the injection port to avoid dislodging plastic material 
into the IV bag. 
9. Administer the calculated dosing volume of reconstituted 
ABRAXANE suspension by IV infusion over 30 minutes.  The use of 
in-line filters is not recommended because the reconstituted solution 
may clog the filter. 
 
5.2.2. Carboplatin 
 
Subjects will receive carboplatin at an AUC of 6 on day 1 of a 21 day cycle. 
 
Carboplatin is a standard treatment for NSCLC. Carboplatin is administered after 
ABRAXANE by intravenous infusion over 60 minutes with standard antiemetics 
per local practice guidelines.  The carboplatin dose will be calculated per 
institutional standards. 
 
5.3. 
Duration of Therapy/Treatment Discontinuation 
 
In the absence of treatment delays due to adverse event(s), treatment may continue 
for up to six cycles or until one of the following criteria applies: 
 
• Disease progression; 
• Intercurrent illness that prevents further administration of 
treatment; 
• Unacceptable adverse event(s); 
• Subject decides to withdraw consent  for the study therapy; 
• General or specific changes in the subject's condition render the subject 
unacceptable for further treatment in the judgment of the investigator; 
• Subject non-compliance 
 
Subjects who discontinue their treatment early are still considered to be on-study 
and may continue to participate in study procedures (e.g. labs, scans, follow-up). 


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5.4. 
Follow-Up 
 
Subjects will be followed until death, three years of follow-up have occurred or lost 
to follow-up following cessation of treatment.  Subjects (or their family members or 
designees) may be contacted by telephone or in writing or during clinic visits after 
treatment discontinuation for collection of follow-up data every six months until 
death or lost to follow-up. Follow-up clinical information may also be obtained 
through chart reviews.  Subjects who discontinued treatment for unacceptable 
adverse events will be followed until resolution or stabilization of the adverse event 
according to standard of care procedures.  Subjects who discontinue treatment for 
any reason will continue follow-up. 
 
5.5. 
Off-Study 
 
Subjects will be considered off study for any of the following reasons: 
• Completion of 3 years of follow-up from enrollment date 
• Consent withdrawal 
• Determination by Principal Investigator 
• Lost to follow up 
• Death 
 
Off study subjects will not receive study treatment or participate in any study 
procedures, including data collection. 
 
5.5.1. Subject Withdrawals 
 
Subjects are defined as withdrawn from the study if they revoke consent for both 
treatment and study procedures or the Investigator withdraws them from the study. 
Subjects must be withdrawn from the trial for the following reasons: 
 
• Subject withdraws consent from study treatment and study procedures. A 
subject must be removed from the trial at his/her own request. At any time 
during the trial and without giving reason, a subject may decline to 
participate further. The subject will not suffer any disadvantage as a result. 
• Subject is lost to follow-up after three consecutive months of attempted 
contact. 
 
Subjects may be withdrawn from the study by the Investigator for the following 
reasons: 
 
• The subject is non-compliant with study drug, study procedures, or both 
(as determined by the Investigator); including the use of anti-cancer 
therapy not prescribed by the study protocol. 


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• Development of an intercurrent illness or situation which would, in the 
judgment of the Investigator, significantly affect assessments of clinical 
status and trial endpoints. 
 
Any subject who withdraws themselves or who is withdrawn from the study by the 
Investigator will remain under medical supervision until discharge or transfer is 
medically acceptable. 
 
In all cases, the reason for withdrawal must be documented in the subject's medical 
records and in the CTMS.  Withdrawn subjects are considered to be off-study. 
 
 
5.6  Screen Failures and Subject Replacements 
 
Enrolled subjects who have discontinued treatment or who have withdrawn after 
receiving their first dose of study drug will not be replaced. A consented subject 
who, for any reason (e.g. failure to satisfy the selection criteria or withdraws 
consent), terminates participation in the study before receiving first dose of study 
drug is regarded as a “screen failure.” Screen Failures may be replaced.  
 
All screen failures will be tracked in the CTMS. 
 
Note that enrolled subjects who do not meet all of the criteria to be included in the 
efficacy population (defined in Section 13.3) will be included in the safety 
population (defined in Section 13.3).  However, these subjects will not contribute 
to the evaluable population and therefore enrollment of subjects will continue until 
the total expected accrual of evaluable subjects has been reached.  
 
 
6. 
STUDY PROCEDURES 
 
6.1. 
Informed Consent 
 
Written informed consent will be obtained from each subject prior to undergoing 
protocol-specific evaluations and prior to receiving treatment. Women will be 
counseled regarding risk of teratogenicity and need to use contraception through the 
course of the study.  Men will also be counseled on the need to use contraception 
for all sexual encounters. 
 
6.2. 
Demographics and Medical/Treatment History 
 
A complete medical history will be obtained at baseline, including smoking history. 
Any clinically significant pre-existing toxicity will also be documented in the 
medical record and recorded on the eCRF.  Medical history will be obtained within 


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30 days prior to the first dose of study medication. ECOG performance status will 
be documented at baseline. 
 
6.3. 
Physical Examination 
 
Evaluation by body system, height (pre-treatment only), weight, and body surface 
area (BSA) will be documented in the medical record and recorded on the eCRF. 
Vital signs will be recorded and include temperature, blood pressure, pulse rate, 
respiratory rate, and oxygen saturation.  ECOG performance status will be assessed. 
 
6.4. 
Pregnancy Test 
 
A serum or urine pregnancy test will be performed at eligibility screening, within 72 
hours prior to starting study drug treatment, and as clinically indicated for women 
of childbearing potential. 
 
6.5. 
Symptoms and Toxicities 
 
All adverse and serious adverse events will be documented in the medical record 
and recorded on the eCRF regardless of attribution on an ongoing basis throughout 
the study. 
 
6.6. 
Concomitant Medications 
 
Any medications other than ABRAXANE and carboplatin will be considered a 
concomitant medication and dose, route, frequency, administration and start/stop 
dates will be documented in the medical record and recorded in the eCRF. 
 
6.7. 
Clinical Laboratory Tests 
 
The blood-based clinical laboratory tests will include a complete blood count with 
differential and platelets, a complete metabolic panel (including sodium, potassium, 
chloride, bicarbonate, BUN, creatinine, glucose, calcium, albumin, total protein, 
total bilirubin, AST, ALT, alkaline phosphatase), magnesium, phosphorus, and 
LDH.  CBC with differential will be obtained at baseline and weekly prior to each 
dose of ABRAXANE. Additional labs including CMP, LDH, magnesium, and 
phosphorus will be obtained at baseline and every three weeks prior to each cycle 
with carboplatin plus ABRAXANE. CBC with differential, CMP, LDH, 
magnesium, and phosphorus will be repeated at cycle 1, day 1 if baseline labs are 
not within 7 days prior to start of study treatment. CBC with differential, CMP, 
LDH, magnesium, and phosphorus will be obtained at end of treatment assessment. 
Laboratory results will be recorded on the eCRF. 
 
 


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6.8. 
Electrocardiogram 
 
A standard electrocardiogram (EKG/ECG) will be required at baseline. 
 
6.9. 
Radiology and Tumor Measurements 
 
A CT (computed tomography) scan with contrast of the chest, pelvis and abdomen 
will be performed according to the schedule outlined in Section 6.12. Tumor 
measurements will be recorded on the eCRF. 
 
6.10. Tissue and Blood-based Biomarkers 
 
The rationale for tissue-based biomarker analysis includes the possibility of 
identifying predictive markers of benefit from carboplatin and/or ABRAXANE. 
Biopsies of tumors from the primary lesion and/or lymph node and/or metastatic 
site will be collected for exploratory analyses of biomarkers after subject 
enrollment, but prior to the first dose of study drug. Archival tumor tissue, for 
which adequate tissue for biomarker testing on prior biopsies may be acceptable, 
will be obtained when possible. Archival tumor tissue must have been obtained 
within the past 60 days and prior to any treatment and will be reviewed by the 
Investigator.  If the archive sample is of insufficient quality or amount, a new core 
biopsy will be required. New biopsies will be fresh-frozen, collected and stored in 
the CHS Biospecimen Repository for batch analysis at the end of the study. 
 
A baseline blood sample will be collected with additional blood collected at the 
subsequent time points according to the Study Calendar in Section 6.12, using one EDTA 
10 mL tube and two 9 mL CPT tubes for blood cell separation and storage.  
For investigational sites unable to process peripheral blood mononuclear cells 
(PBMCs), obtain two EDTA 10 mL tubes only. Specimens will be delivered to the 
CHS Biospecimen Repository to be processed within one hour of collection, and 
stored for batch analysis at the end of the study. 
 
Levine Cancer Institute will analyze biomarkers in both tissue and blood including 
those relative to treatment and response (e.g., immunophenotyping, biomarkers 
related to immune balance, etc.). The immunology biomarker analysis will be 
performed in the Immune Monitoring Core Laboratory at Cannon Research Center, 
Carolinas Medical Center in Charlotte, NC (c/o Dr. David Foureau). These studies 
will be defined in a future related IRB-approved laboratory research protocol. 
 
6.11. Subsequent Anti-cancer Therapy and Survival Status 
 
Subject’s cancer therapies and survival status following completion of treatment 
will be recorded in the eCRF. 


20 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
6.12. Study Calendar 
 
Required Procedures 
Baseline 
During Treatment 
End of Treatment 
Follow-Up 
Within 30 days 
Every 3 weeks, ± 7 
Within 30 days after 
Every 6 months 
prior to treatment 
days, unless 
the last dose of study 
until death or lost 
initiation unless 
otherwise specified 
medication unless 
to follow-up 
otherwise specified 
otherwise specified 
Informed consent 
X 
Demographics 
X 
Medical and Treatment 
Xf
History 
Physical Exam, Vital 
X 
X 
X 
Signs, Oxygen Saturation 
Pregnancy Test 
(serum or urine)a 
X 
Within 72 hours 
prior to starting 
If/when clinically 
indicated 
study drug and 
if/when clinically 
indicated 
Symptoms & Toxicities 
X 
X 
X 
Concomitant 
X 
X 
X 
Medications 
Laboratory Tests 
Xb 
Xb 
Xb 
EKG/ECG 
X 
Radiology & Tumor 
X 
X 
X 
Xc 
Measurements 
Every 6 weeks, ± 14 
days 
Biopsy Tissue 
Collection for 
Xd 
Prior to treatment 
Biomarkers 
initiation 
Blood-based Biomarkers 
X 
Xe 
X 
 
Within 30 days 
Pre-dose on day 1 of 
 
 
prior to treatment 
treatment cycles  
 
 
initiation 
3, and 5. 
Subsequent Anticancer 
X 
Therapy 
Survival Status 
X 
a: In women of child-bearing potential 
b: CBC with differential will be obtained at baseline and weekly prior to each ABRAXANE dose. CMP, LDH, 
magnesium, and phosphorus will be obtained at baseline and every three weeks prior to each cycle of 
carboplatin plus ABRAXANE dose. CBC with differential, CMP, LDH, magnesium, and phosphorus will be 
repeated at cycle 1, day 1 if baseline labs are not within 7 days prior to start of study treatment. 
CBC/differential, CMP, LDH, magnesium, and phosphorus will be obtained at end of treatment assessment. 
c: Per standard surveillance guidelines, as clinically  
indicated.  
d: See Section 6.10 for tissue collection requirements. 
e: Pre-dose on day 1 of treatment cycles 3, and 5 and per Section 6.10. 
    f: includes smoking history at baseline only 


21 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
7. 
REQUIRED EVALUATIONS 
 
7.1. 
Pre-Treatment Evaluations 
 
Pre-treatment evaluation will include screening (to determine subject eligibility), 
medical history (including smoking history at baseline), physical examination, vital signs, 
clinical laboratory tests as described in Section 6, as well as adverse events assessment.  
Fresh or archived tumor biopsies are required prior to treatment initiation.  Blood 
samples for biomarker testing will be obtained prior to treatment initiation. 
 
Imaging tests, including comprehensive (at least chest, abdomen, and pelvis) contrast-
enhanced CT or MRI aimed at defining the extent of existing disease must be 
performed and documented within 30 days prior to the first dose of study therapy.  An 
EKG/ECG must also be performed and documented prior to treatment initiation. 
 
A negative pregnancy test for all women of childbearing potential must be documented 
before initiating treatment. 
 
Written informed consent must be obtained prior to any study-specific screening 
evaluations and prior to receiving treatment. 
 
7.2. 
Treatment Period 
 
Prior to each on-study infusion, vital signs and CBC/differential/platelets will be 
obtained. 
 
Vital signs, weight measurements, toxicity, concomitant medications and adverse 
events assessments, physical examination, and laboratory tests (hematology and 
chemistry profiles) will be performed within 7 days of day 1 of each cycle. 
 
Imaging studies and tumor response assessments will be repeated every 6 weeks (± 2 
weeks), or as clinically indicated. 
 
After initiating study treatment (cycle 1 day 1), blood samples for biomarker testing will 
be obtained every 6 weeks (± 2 weeks). 
 
7.3. 
End of Therapy 
 
Every subject will undergo an end-of-therapy evaluation at the time it is determined that 
he or she is no longer eligible to receive study therapy.  End of 


22 
 Protocol Number:  LCI-LUN-ABR-001 
Version -2:  November 11, 2015 
 
 
 
therapy evaluations will include vital signs, weight measurements, toxicity, 
concomitant medications and adverse events assessments, physical examination, 
and laboratory tests (hematology and chemistry profiles) as well as imaging studies 
with tumor measurements and blood for biomarker testing. The end of therapy 
evaluation must be completed within 30 days after treatment discontinuation. 
 
7.4. 
Follow-Up/Survival Period 
 
All subjects will be followed until all treatment-related toxicities have resolved, 
returned to baseline, stabilized, or are deemed irreversible according to standard of 
care procedures. 
 
Subjects may be contacted by telephone or in writing, or during clinic visits after 
treatment discontinuation for collection of follow-up information approximately 
every 6 months until death or lost to follow-up. Follow-up clinical information may 
also be obtained through chart reviews. 
 
Imaging studies and tumor assessments will be attempted per standard surveillance 
guidelines (which may be as frequently as every 6 weeks ± 2 weeks) until 
documented progression for subjects who had a complete response, partial response, 
or stable disease, and/or discontinued study therapy due to toxicity or reasons other 
than progressive disease. 
 
 
 
8. 
DOSING DELAYS/DOSE MODIFICATIONS 
 
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will 
be utilized for grading toxicities. A copy of the CTCAE Version 4.0 can be 
downloaded from the CTEP homepage 
(http://ctep.cancer.gov/protocol/Development/electronic_applications/ctc.htm#ctc_40). 
All adverse clinical experiences, whether observed by the Investigator or reported 
by the subject, must be recorded, with details about the duration and intensity of 
each episode, the action taken with respect to the study drug, and the subject’s 
outcome. The Investigator must evaluate each toxicity for its relationship to the 
study drug and severity. 
 
8.1. 
Dose Modifications for ABRAXANE 
 
Management of severe or intolerable adverse reactions may require dose reduction 
and/or interruption of ABRAXANE. Recommendations of dose reduction, 
interruption or discontinuation in the management of adverse reactions are 
summarized in Table 1. Clinical judgment of the Investigator should guide the 
management plan of each subject based on individual benefit/risk assessments. 


23 
 Protocol Number:  LCI-LUN-ABR-001 
Version -2:  November 11, 2015 
 
 
 
Table 1: Pre-specified dose/schedule modifications for adverse events related to 
ABRAXANE 
 
Dose Level 
Dose of ABRAXANE (mg/m2) 
0 
100 
-1 
75 
-2 
50 
 
Recommendations for dose reduction, interruption, or discontinuation in the management 
of ABRAXANE-related adverse events are outlined in Table 2. 
 
Table 2: Criteria for dose modifications for ABRAXANE-related toxicities 
 
Toxicity 
Dose Modification 
Abnormal Hematologic Function 
• ANC ≤ 1.5 x 109 cells/L and platelets 
<100 x 109 cells/L 
• ANC ≤ 1.0 x 109 cells/L and platelets < 
75 x 109 cells/L. 
• Level 0 ABRAXANE dose should not 
be administered at the start of each 
cycle unless ANC criteria are met. 
• Subjects must meet ANC and platelet 
criteria for subsequent ABRAXANE 
doses (days 8 and 15). If the ANC and 
platelets are not adequate for treatment 
on Day 8 and/or 15, the dose will be 
held and the total cycle length remains 
the same. 
Refer to Table 3 for information on dose 
reductions and guidelines for optimal use 
of growth factors for hematologic toxicity. 
Abnormal Hepatic Function 
• AST and ALT < 2.5x upper limit of 
normal, alkaline phosphatase < 2.5x 
upper limit of normal, unless bone 
metastasis is present in the absence of 
liver metastasis. 
• Maintain level 0 dose level (see Table 
1). Hepatic toxicity from taxanes may 
occur but is uncommon.  Therefore, 
hepatic dysfunction that occurs while 
the subject is on study should prompt an 
evaluation to determine the cause, 
including the possibility of progressive 
metastatic disease and hepatotoxicity 
from concurrent medications. 


24 
 Protocol Number:  LCI-LUN-ABR-001 
Version -2:  November 11, 2015 
 
 
 
Sensory Neuropathy 
• ≥ Grade 3 
• ≥ Grade 4 
• Withhold ABRAXANE. Treatment 
may be resumed at the next lower dose 
level (see Table 1) in subsequent cycles 
after the sensory neuropathy improves 
to Grade 1. The time to resolution to 
≤ Grade 1 should be the adverse event 
duration used for adverse event 
reporting.  Note: The investigator may 
elect to dose modify for Grade 3 
sensory neuropathy. 
• Withhold ABRAXANE. Treatment 
may be resumed at a reduction of 2 
dose levels (Dose Level -2; see Table 1) 
in subsequent cycles after the sensory 
neuropathy improves to Grade 1. 
Hypersensitivity Reactions 
• Minor symptoms such as flushing, skin 
reactions, dyspnea, lower back pain, 
hypotension, or tachycardia. 
• Severe reactions, such as hypotension 
requiring treatment, dyspnea requiring 
bronchodilators, angioedema or 
generalized urticaria. 
• Temporarily interrupt ABRAXANE 
infusion according to institutional 
standards. 
• Immediately discontinue ABRAXANE 
administration and begin aggressive 
symptomatic therapy. Subjects who 
experience severe hypersensitivity 
reactions to ABRAXANE should not be 
re-initiate treatment. 
It is not recommended to administer 
ABRAXANE to subjects with prior 
hypersensitivity to a taxane. 
Other toxicities 
• Grade 3, except for anemia 
• Treatment should be withheld until 
resolution to grade 1 or baseline if 
baseline was greater than grade 1, then 
reinstituted, if medically appropriate, at 
the next lower dose level (see Table 1). 


25 
 Protocol Number:  LCI-LUN-ABR-001 
Version -2:  November 11, 2015 
 
 
 
G-C SFAdministration 
Administer G-CSF 5 mcg/kg/day (rounded to the nearest vial size per investigator/ 
institution’s standard of care) 24 hours after chemotherapy and hold 48 hours prior 
to the next dose. 
 
Table 3:  Use of G-CSF and Dose reductions for Hematologic Toxicity 
Toxicity 
Occurrence 
Action to be Taken 
ANC < 500 cells/mm3 
(nadir count) with 
neutropenic fever > 38° C 
OR 
Delay of next cycle due to 
persistent neutropenia 
(ANC < 1500 cells/mm3) 
OR 
For subjects on weekly 
treatment whose next 
treatment within the cycle 
(Day 8 or Day 15) is 
omitted due to persistent 
neutropenia 
(ANC < 1000 cells/mm3) 
(i.e. ANC still <1000 
cells/mm3 after previous 
week’s omission) 
OR 
Neutropenia 
< 500 cells/mm3 for > 1 
week 
• Thrombocytopenia 
Grade 3 or Grade 4 
Any 
Occurrence 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1st 
Occurrence 
 
Recurrence 
At the first occurrence of a 
hematological toxicity (as outlined in 
the Toxicity column), the same dose is 
maintained and granulocyte colony- 
stimulating factor (G-CSF) is given as 
outlined below.  In the event that a 
hematological toxicity re-occurs in the 
face of G-CSF, dose reduction to the 
next lower level will be required for 
subsequent cycles once ANC is 1500 
cells/mm3. 
 
If G-CSF is given concurrently with 
weekly ABRAXANE, administration 
may begin the day after ABRAXANE is 
given and should stop at least 48 hours 
prior to when ABRAXANE is given the 
following week. 
 
 
 
 
 
• Dose reduction to next lower level. 
 
 
 
• Dose reduction to next lower level. 


26 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
 
Concomitant Medications 
Supportive care, including but not limited to anti-emetic medications, may be 
administered at the discretion of the investigator.  Concurrent treatment with 
bisphosphonates is allowed.  Erythropoietin may be administered at the discretion of the 
Investigator, consistent with institutional guidelines. 
 
Caution should be used when concomitantly administering ABRAXANE with 
inhibitors (e.g., ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
gemfibrozilm cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) or inducers 
(e.g., rifampicin, carbamazepine, phenytoin, efavirenz, and nevirapine) of either 
CYP2C8 or CYP3A4.) 
 
8.2. 
Dose Modifications for Carboplatin 
 
Dose modifications for carboplatin can be made at the Investigator’s discretion in 
accordance with the package insert and institutional standards. 
 
9. 
SAFETY DATA COLLECTION, RECORDING AND REPORTING 
 


27 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
Safety assessments will consist of monitoring and recording all adverse events and 
serious adverse events, the regular monitoring of hematology, blood chemistry values, 
and regular measurement of vital signs and the performance of physical examinations. 
These assessments should be performed within ± 7 days of the scheduled day of 
assessment except for adverse events which will be evaluated continuously through the 
study. Safety and tolerability will be assessed according to the Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.0. All adverse events (Grades 1 – 5) 
will be recorded on the eCRF. 
 
9.1. 
Unanticipated Problem (UAP) Definition 
 
An Unanticipated Problem (UAP) is any incidence, experience or outcome that is 
unexpected, given the information provided in research-related documentation (e.g. 
investigator’s brochure, informed consent), related or possibly related to participation in 
the research and the study population characteristics that is related or possibly related to 
participation in the research study and places the participant at an increased risk. 
 
9.2. 
Adverse Event (AE) Definition 
 
An adverse event or adverse experience is any untoward medical occurrence in a study 
subject who is administered a study drug that does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and 
unintended sign, symptom, or disease temporally associated with the use of the study 
drug, whether or not considered related to the study drug. 
Pre-existing conditions that increase in frequency or severity or change in nature during 
or as a consequence of use of a drug in human clinical trials are also considered adverse 
events.  Adverse events may also include pre or post-treatment complications that occur 
as a result of protocol-mandated procedures (e.g., invasive procedures such as biopsies). 
 
Any continuing medical condition or clinically significant laboratory abnormality with an onset 
date before the first date of study drug administration should be considered pre-existing 
and should be documented. 
 
An AE does not include: 
• Relapse or progression of the underlying malignant disease; however, the 
associated signs, symptoms, or diagnoses should be recorded as adverse 
events (e.g., “jaundice” due to new or increasing liver metastases, or “tumor 
pain” or “bone pain” due to progressive disease); 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, 
transfusion).  The condition that leads to the procedure is the adverse event; 
• Situations where an untoward medical occurrence has not occurred (e.g., 
hospitalization for elective surgery, social and/or convenience 
admissions); 
• Overdose of either study drug or concomitant medication without any signs or 
symptoms unless the subject is hospitalized for observation; and 


28 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
• Pregnancy. (Must be reported as an SAE.) 
 
Laboratory abnormalities are usually not recorded as adverse events; however, signs 
and/or symptoms that are associated with laboratory findings requiring study 
withdrawal, dose modification, or medical intervention (e.g., anemia requiring 
transfusions or hyperglycemia requiring treatment) or other abnormal assessments (e.g., 
ECG, radiographs, vital signs) must be recorded as adverse events if they meet the 
definition of an adverse event.  In addition, laboratory abnormalities marked as 
clinically significant by the investigator should also be recorded as adverse events in the 
eCRF.  The investigator will record the most severe grade of the clinically significant 
laboratory abnormality and will evaluate its relationship to the study drug and clinical 
condition if/when a clinically significant laboratory abnormality occurs. 
 
The relationship to study drug therapy should be assessed using the following 
definitions: 
 
Not Related:  Evidence exists that the AE has an etiology other than the study drug 
(e.g., pre-existing condition, underlying disease, intercurrent illness, or concomitant 
medication).  This includes events that are considered remotely or unlikely related to 
study drug. 
 
Related:  A temporal relationship exists between the event onset and administration of the 
study drug.  It cannot be readily explained by the subject’s clinical state, intercurrent illness, or 
concomitant therapies.  In the case of cessation or reduction of the dose, the event abates or 
resolves and reappears upon rechallenge.  It should be emphasized that ineffective study drug 
treatment should  not be considered as causally related in the context of AE reporting.  
This includes events that are considered possibly, probably, or definitely related to 
study drug. 
 
All adverse events (including event name, grade, start/stop date and attribution) will be 
documented in the medical record and on the eCRF for this protocol. 
 
The Investigator is responsible for verifying and providing source documentation for all 
adverse events and assigning the attribution for each event for all subjects enrolled on 
the trial. 
 
9.3. 
Suspected Adverse Reaction (SAR) Definition 
 
A SAR is an adverse event in which there is reasonable possibility that the study drug 
caused the adverse event as defined by 21 CFR 312.32.  The Investigator is responsible 
for judging whether it is a reasonable possibility that the study drug caused the adverse 
event. 
 
9.4. 
“Unexpected” Definition 
 


29 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
An AE or SAR is to be considered unexpected if the event is not listed in the 
investigator brochure or is not listed in the severity or specificity observed. 
 
9.5. 
“Serious” and “Life-Threatening” Definitions 
 
An AE or SAR is to be considered serious if the Investigator or Sponsoring Company 
deems it as such and the event results in any of the following outcomes: 
 
• 
Death; 
• 
Life-threatening situation (subject is at immediate risk of death); 
• 
Inpatient hospitalization or prolongation of an existing hospitalization (excluding those 
for study drug administration, protocol-related procedures, palliative or hospice care, or 
placement of an indwelling catheter, unless associated with other serious events); 
• 
Persistent or significant disability/incapacity; 
• 
Congenital anomaly/birth defect in the offspring of a subject who received study drug; 
Other:  Important medical events that may not result in death, be immediately life-
threatening, or require hospitalization, may be considered an SAE when, based upon 
appropriate medical judgment, they may jeopardize the subject or may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples of 
such events are: 
 
o Intensive treatment in an emergency room or at home for allergic bronchospasm; 
o Blood dyscrasias or convulsions that do not result in hospitalization; 
o Development of drug dependency or drug abuse. 
 
An AE or SAR is to be considered life-threatening if the Investigator or Funding 
Company deems it as such and the event poses an immediate threat of death. 
 
9.6. 
Serious Adverse Event (SAE) Definition 
 
A serious adverse event is any untoward medical occurrence that at any dose: 
 
• 
Results in death,  
• 
Is life-threatening, 
• Requires inpatient hospitalization or prolongation of existing hospitalization, 
• Results in persistent or significant disability/incapacity, or  
• Is a congenital anomaly/ birth defect 
SAE will be reported to Celgene Corporation within twenty-four (24) hours of LCI 
becoming aware of the event or non-serious adverse drug reactions, as may be required. 
Any correspondence to the FDA related to adverse event reporting will be 
simultaneously copied to Celgene. 
 
SAEs will be captured from the time the subject is enrolled through 30 days after the 
date of the last study drug administration. SAEs will be followed until clinical recovery 


30 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
is complete and laboratory tests have returned to baseline, until progression has been 
stabilized, or until there has been acceptable resolution of the event. This may at times, 
cause the follow-up period for SAEs to be greater than 30 days.  The above referenced 
30-day time period applies even if the subject is taken off study and enrolled onto 
another protocol during this time period. Similarly, the Investigator is responsible for 
following the subject during the required follow-up period even if the subject lives 
elsewhere or has been released from his or her care and is being treated under another 
service at LCI. 
 
Laboratory abnormalities: 
Laboratory abnormalities that meet the definition of a serious adverse event will 
be recorded as such the eCRF and reported appropriately. The Investigator will record 
the most severe grade of the clinically significant laboratory abnormality and will 
evaluate its relationship to the study drug and clinical condition if/when a clinically 
significant laboratory abnormality occurs. 
 
Planned hospitalizations: 
Elective surgeries that have been planned prior to subject enrollment in the study 
or for conditions existing prior to study enrollment do not need to be captured as SAEs, 
unless complications occur or the conditions are worse that the subject’s baseline. They 
should however be clearly documented in the eCRF. 
 
Hospital admission for treatment required by the protocol need not be reported as  
an SAE, unless a complication results that fits the 21CFR 312.32 definition of a SAE. 
 
Development of New Cancers: 
Secondary malignancies are defined as new cancers, not transformations or 
progression of original disease. 
 
Secondary malignancies during 30 day time period after treatment 
discontinuation 
Any secondary malignancy diagnosed within 30 days of the last dose, regardless 
of attribution, must be reported as an SAE. The pathology report documenting the new 
malignancy should be retained in the subject’s research chart and in the medical record. 
 
Secondary malignancies after the 30 day time period after treatment 
discontinuation 
Any secondary malignancy diagnosed greater than 30 days after last day of study 
drug and thought to be possibly, probably or definitely related to drug must be reported 
as an SAE. The pathology report documenting the new malignancy should be attached. 
 
Deaths: 
Deaths during 30 day time period after treatment discontinuation 
Any death, expected or unexpected, occurring within 30 days of the last dose of 
study drug, regardless of attribution, must be reported as an SAE. 


31 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
 
Deaths after the 30 day time period after treatment discontinuation 
Deaths occurring greater than 30 days after last day of study drug and thought to 
be possibly, probably or definitely related to drug must be reported within 24 hours of 
knowledge of the event. 
 
Pregnancies: 
Pregnancies and suspected pregnancies (including a positive pregnancy test 
regardless of age or disease state) of a female subject occurring while the subject is in 
treatment, or within 28 days of the subject’s last dose of study drug, are considered 
immediately reportable events. ABRAXANE is to be discontinued immediately. The pregnancy, 
suspected pregnancy, or positive pregnancy test must be reported as an SAE and reported to 
Celgene Drug Safety immediately by facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form. The female subject may be 
referred to an obstetrician-gynecologist (not necessarily one with reproductive toxicity 
experience) or another appropriate healthcare professional for further evaluation. 
 
The Investigator will follow the female subject until completion of the pregnancy, and 
must notify Celgene Drug Safety immediately about the outcome of the pregnancy 
(either normal or abnormal outcome) using the Pregnancy Follow-up Report Form, or 
approved equivalent form. 
 
If the outcome of the pregnancy was abnormal (e.g., spontaneous or therapeutic 
abortion), the Investigator should report the abnormal outcome as an AE. If the 
abnormal outcome meets any of the serious criteria, it must be reported as an SAE 
to Celgene Drug Safety immediately by facsimile, or other appropriate method, 
within 24 hours of the Investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form. 
 
All neonatal deaths that occur within 28 days of birth should be reported, without regard 
to causality, as SAEs. In addition, any infant death after 28 days that the Investigator 
suspects is related to the in utero exposure to ABRAXANE should also be reported to 
Celgene Drug Safety immediately by facsimile, or other appropriate method, within 24 
hours of the Investigator’s knowledge of the event using the SAE Report Form, or 
approved equivalent form. 
 
Male Subjects: 
If a female partner of a male subject taking ABRAXANE becomes pregnant, the male 
subject taking ABRAXANE should notify the Investigator, and the pregnant female 
partner should be advised to call their healthcare provider immediately. Male patients 
treated with nab-paclitaxel are advised not to father a child and up to 6 months after 
treatment. 
 
Overdose: 


32 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
Overdose, as defined for this protocol, refers to ABRAXANE dosing only.  On a per 
dose basis, an overdose is defined as the following amount over the protocol-specified 
dose of ABRAXANE assigned to a given patient, regardless of any associated adverse 
events or sequelae.  
PO-any amount over the protocol-specified dose  
IV- 10% over the protocol-specified dose   
SC-10% over the protocol-specified dose  
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency. 
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-
specified rate.  For nab-paclitaxel, an infusion completed in less than 25 minutes may 
increase Cmax by approximately 20%, therefore a nab-paclitaxel infusion completed in 
less than 25 minutes will meet the infusion rate criterion for an overdose.  Complete 
data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form.  
Celgene Drug Safety Contact Information: 
Celgene Corporation      
Global Drug Safety and Risk Management    
Connell Corporate Park      
300 Connell Dr.  Suite 6000     
Berkeley Heights, NJ  07922        
Fax: (908) 673-9115 
E-mail: drugsafety@celgene.com 
  
 
Questionable events: 
Any suspected adverse reaction can and should be reported as an SAE if deemed 
appropriate by the Investigator. 
 
All SAEs (including event name, grade, start/stop date and attribution) will be 
documented in the medical record and on the eCRF. 
 
The Investigator is responsible for verifying and providing source documentation for all 
SAEs and assigning the attribution for each event for all subjects enrolled on the trial. 
 
9.7. 
Safety Reporting to the Sponsor (Levine Cancer Institute) 
 
All events occurring during the conduct of the study and meeting the definitions of a UAP or 
SAE will be reported promptly to the Sponsor, but no later than 2 business days from the time 


33 
Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
the Investigator learns of the event. Applicable events must be reported via the CTMS with a 
notification to the Protocol Coordinator and Sponsor-Investigator. 
Deviations involving the informed consent process or subject safety will be reported 
promptly to the Sponsor, but no later than 5 business days from the time the Investigator 
learns of the event. Applicable events must be reported via the CTMS with a 
notification to the Protocol Coordinator and Sponsor-Investigator. 
 
9.8. 
Safety Reporting to the IRB 
 
All events occurring during the conduct of a protocol and meeting the definition of an 
UAP or SAE will be reported to the IRB promptly, but no later than 2 weeks from the 
time the Investigator learns of the event. 
 
Deviations involving the informed consent process or subject safety will be reported 
promptly to Chesapeake IRB but no later than two weeks from the time of identification 
of the deviation by the Investigator. 
 
9.9. 
Safety Reporting to Celgene Corporation 
 
Non-serious adverse events will be reported to Celgene bi-annually (or upon request by 
Celgene), in accordance with 21 CRF 312.64. 
 
When the Investigator has determined that a SAE has occurred, the Investigator is 
responsible for providing information regarding the SAE to Celgene in writing using a 
Celgene SAE form or MEDWATCH 3500A form of any SAE within 24 hours of being 
aware of the event. The written report must be completed and supplied to Celgene by 
facsimile within 24 hours/1 business day. The initial report must be as complete as 
possible, including an assessment of the causal relationship between the event and the 
investigational product(s), if available. Information not available at the time of the 
initial report (e.g., an end date for the adverse event or laboratory values received after 
the report) must be documented on a follow-up report. A final report to document 
resolution of the SAE is required. The Celgene tracking number (AX-CL-NSCLC-PI-
004075) and the institutional protocol number (LCI-LUN-ABR-001) should be 
included on SAE reports (or on the fax cover letter) sent to Celgene. A copy of the fax 
transmission confirmation of the SAE report to Celgene should be attached to the SAE 
and retained with the patient records. 
 
Celgene Corporation 
Global Drug Safety and Risk Management Connell 
Corporate Park 
300 Connell Drive Suite 6000 
Berkeley Heights, NJ 07922 
Fax number: 908-673-9115 
Email: d r u g s a f e t y @ c e l g e n e.c o m 
 


34 
Protocol Number:  LCI-LUN-ABR-001
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Deviations involving subject safety will be reported to Celgene promptly but no later 
than two weeks from the time of identification of the deviation by the Investigator. 
 
Protocol deviations that are minor or administrative will be reported to Celgene bi-
annually. 
 
10. 
TREATMENT-RELATED ADVERSE EVENTS 
 
Subjects will be closely monitored for treatment-related adverse events.  Adverse event 
monitoring will occur on a continuous basis for the duration that subjects are on study 
therapy.  In addition to the planned evaluations during follow-up visits, subjects will be 
instructed to call their physician to report any adverse events between visits. 
 
10.1. Carboplatin 
 
Anaphylactic reactions have occurred with carboplatin injections. Adequate medical 
supervision must be present and appropriate intervention must be readily available to 
diagnose and treat hypersensitivity reactions.   Bone marrow suppression is the dose 
limiting toxicity, and is increased in subjects with impaired renal function.  It is dose 
dependent. Thrombocytopenia with platelet 
counts below 50 x 109 cells/L occurs in 25% of subjects and neutropenia with 
granulocyte counts below 1.0 x 109 cells/L occurs in 16% of subjects.  Anemia is 
cumulative and transfusions may be necessary in subjects receiving prolonged therapy.  
Cycles should not be repeated until neutrophils and platelet counts have recovered.  
Nausea, vomiting, and neurotoxicity are other common drug-related adverse events. 
Other common side effects of carboplatin include nausea, vomiting, appetite loss, 
hypokalemia, and hypomagnesemia. 
 
10.2. ABRAXANE 
 
The following adverse events have been described with ABRAXANE treatment: 
myelosuppression, nausea and vomiting, diarrhea, mucositis, infections, hypotension, 
abnormal ECG changes, cough, dyspnea, edema, sensory neuropathy, bilirubin/liver 
enzyme elevations, allergic reactions, alopecia, asthenia, arthralgia, and myalgia. 
During post marketing surveillance, rare cases of severe hypersensitivity reactions have 
occurred.


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Protocol Number:  LCI-LUN-ABR-001
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Table 10.2.1: Frequencya of Important Treatment Emergent Adverse Events in the 
Randomized Study on a Q3W Schedule 
ABRAXANE 
260/30minb 
(% of n=229) 
Paclitaxel Injection 
175/3hc,d 
(% of n=225) 
Bone Marrow 
Neutropenia 
80 
82 
< 2.0 x 109/L 
< 0.5 x 109/L 
9 
22 
Thrombocytopenia 
2 
3 
< 100 x 109/L 
< 50 x 109/L 
<1 
<1 
Anemia 
33 
25 
< 11 g/Dl 
< 8 g/Dl 
1 
<1 
Infections 
24 
20 
Febrile Neutropenia 
2 
1 
Bleeding 
2 
2 
Hypersensitivity Reactione 
All 
4 
12 
Severef 
0 
2 
Cardiovascular 
Vital Sign Changesg 
Bradycardia 
<1 
<1 
Hypotension 
5 
5 
Severe Cardiovascular 
Eventsf 
3 
4 
Abnormal ECG 
All subjects 
60 
52 
Subjects with Normal 
Baseline 
35 
30 
Respiratory 
Cough 
7 
6 
Dyspnea 
12 
9 
Sensory Neuropathy 
Any Symptoms 
71 
56 
Severe Symptomsf 
10 
2 
Myalgia / Arthralgia 
Any Symptoms 
44 
49 
Severe Symptomsf 
8 
4 


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Protocol Number:  LCI-LUN-ABR-001
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Asthenia 
Any Symptoms 
47 
39 
Severe Symptomsf 
8 
3 
Fluid Retention/Edema 
Any Symptoms 
10 
8 
Severe Symptomsf 
0 
<1 
Gastrointestinal 
Nausea 
Any Symptoms 
30 
22 
Severe Symptomsf 
3 
<1 
Vomiting 
Any symptoms 
18 
10 
Severe Symptomsf 
4 
1 
Diarrhea 
Any Symptoms 
27 
15 
Severe Symptomsf 
<1 
1 
Mucositis 
Any Symptoms 
7 
6 
Severe Symptomsf 
<1 
0 
Alopecia 
90 
94 
Hepatic (Subjects with Normal Baseline) 
Bilirubin Elevations 
7 
7 
Alkaline Phosphatase 
Elevations 
36 
31 
AST (SGOT) 
Elevations 
39 
32 
Injection Site Reaction 
<1 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Based on worst grade 
b ABRAXANE dose in mg/m2/duration in minutes 
c Paclitaxel injection dose in mg/m2/duration in hours 
d Paclitaxel-injection subjects received premedication 
e Includes treatment-related events related to hypersensitivity (e.g., flushing, dyspnea,   
chest pain, hypotension) that began on a day of dosing 
f Severe events are defined as at least grade 3 toxicity 
g During study drug dosing 
 
10.3. Adverse Event Characteristics 
 
CTCAE term (AE description) and grade: The descriptions and grading scales 
found in the revised NCI Common Terminology Criteria for Adverse Events 


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Protocol Number:  LCI-LUN-ABR-001
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(CTCAE) version 4.0 will be utilized for AE reporting.  All Levine Cancer Institute 
staff will have access to a copy of the CTCAE version 4.0. 
 
Attribution of the AE: 
Definite – The AE is clearly related to the study treatment. 
Probable – The AE is likely related to the study treatment. 
Possible – The AE may be related to the study treatment. 
Unlikely – The AE is doubtfully related to the study treatment. 
Unrelated – The AE is clearly NOT related to the study treatment. 
 
11. 
DATA SAFETY AND MONITORING PLAN 
 
11.1. Monitoring 
 
This protocol will be monitored according to the processes in effect for all Levine 
Cancer Institute investigator- initiated studies and the protocol-specific monitoring plan, 
and will abide by standard operating procedures set forth by both the Carolinas 
Healthcare System Office of Clinical and Translational Research and the Levine Cancer 
Institute Clinical Trials Office. It is the responsibility of the Sponsor-Investigator to 
monitor the safety data for this study. The Sponsor-Investigator, Statistician, Protocol 
Coordinator, and other team members as needed will meet regularly to monitor subject 
consents, enrollment and retention, safety data for all subjects [including adverse events 
(AE’s) for all grades and attributions, serious adverse events (SAE’s)], study drug 
administration, and validity/integrity of the data. Documentation of these meetings will 
be kept with study records. SAEs will be reported to the Food and Drug Administration 
(FDA) and the IRB per their requirements. Major protocol deviations that result in a 
threat to subject safety or the integrity of the study will be reported to the FDA and IRB 
per their requirements. The Sponsor-Investigator will submit data to the LCI Data and 
Safety Monitoring Committee according to the overarching LCI Data and Safety 
Monitoring Plan.  
 
11.2. Data Quality Assurance 
 
This trial will be organized, conducted, and reported in compliance with the protocol, 
standard operating procedures (SOPs) of  LCI and Carolinas Healthcare System Office 
of Clinical and Translational Research, the FDA, and other applicable regulations and 
guidelines (e.g. GCP). 
 
Subjects will be monitored by LCI Research /Data Monitors per the study-specific 
monitoring plan and LCI/CHS SOPs for data quality. This monitoring will be done by 
comparing source documentation to the eCRFs. Any variation between the two data sets 
will be discussed with the Protocol Coordinator, Sponsor- Investigator and/or other 
study personnel as appropriate.  


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 Protocol Number:  LCI-LUN-ABR-001
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The trial database will be reviewed and checked for omissions, apparent errors, and 
values requiring further clarification using computerized and manual procedures. 
Data queries requiring clarification will be generated and addressed as needed by 
appropriate study personnel. Only authorized personnel will make corrections to the 
database and all corrections will be documented in an electronic audit trail. 
 
12. 
MEASUREMENT OF EFFECT 
 
12.1. Antitumor Effect 
 
Response and progression will be evaluated in this study using the revised response 
evaluation criteria in solid tumors (RECIST) guideline version 1.1.16 
 
12.1.1. Definitions 
 
Evaluable for toxicity:  All subjects will be evaluable for toxicity from the time of 
their first treatment with ABRAXANE and carboplatin. 
 
Evaluable for efficacy:  Only subjects who have measurable disease present at 
baseline, have received at least one dose of study therapy, and have had their 
disease re-evaluated (either clinically or radiologically) will be considered evaluable 
for efficacy. These subjects will have their objective response classified according 
to the definitions stated below. 
 
 
 
12.1.2. Disease Parameters 
 
Target lesions: When more than one measurable lesion is present at baseline all 
lesions up to a maximum of five lesions total (and a maximum of two lesions per 
organ) representative of all involved organs should be identified as target lesions 
and will be recorded and measured at baseline. Target lesions should be selected on 
the basis of their size (lesions with the longest diameter), be representative of all 
involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the 
largest lesion does not lend itself to reproducible measurement in which 
circumstance the next largest lesion which can be measured reproducibly should be 
selected. Lymph nodes merit special mention since they are normal anatomical 
structures which may be visible by imaging even if not involved by tumor. 
Pathological nodes which are defined as measurable and may be identified as target 
lesions must meet the criterion of a short axis of ≥ 15 mm by CT scan or MRI. Only 
the short axis of these nodes will contribute to the baseline sum. The short axis of 
the node is the diameter normally used by radiologists to judge if a node is involved 
by solid tumor. Nodal size is normally reported as two dimensions in the plane in 
which the image is obtained (for CT scan this is almost always the axial plane; for 


39 
 Protocol Number:  LCI-LUN-ABR-001
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MRI the plane of acquisition may be axial, sagittal or coronal). The smaller of these 
measures is the short axis. All other pathological nodes (those with short axis ≥ 10 
mm but <15 mm) should be considered non-target lesions. Nodes that have a short 
axis <10 mm are considered non-pathological and should not be recorded or 
followed. A sum of the diameters (longest for non-nodal lesions, short axis for 
nodal lesions) for all target lesions will be calculated and reported as the baseline 
sum diameters. If lymph nodes are to be included in the sum, then as noted above, 
only the short axis is added into the sum. The baseline sum diameters will be used 
as reference to further characterize any objective tumor regression in the measurable 
dimension of the disease. 
 
Non-target lesions: All other lesions (or sites of disease) including pathological 
lymph nodes should be identified as non-target lesions and should also be followed 
as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’ (more details to 
follow). 
 
12.1.3. Methods for Evaluation of Measurable Disease 
 
All measurements should be taken and recorded in metric notation using a ruler or 
calipers. All baseline evaluations should be performed as closely as possible to the 
beginning of treatment and never more than 4 weeks before the beginning of the 
treatment. 
 
The same method of assessment and the same technique should be used to 
characterize each identified and reported lesion at baseline and during follow-up. 
Imaging-based evaluation is preferred to evaluation by clinical examination when 
both methods have been used to assess the antitumor effect of a treatment.  The 
Sponsor-Investigator or designee will be responsible for performing tumor 
measurements.  The tumor measurements will be recorded in the eCRF. 
 
12.1.4. Response Criteria 
 
Complete Response (CR): 
Target lesion: Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm. 
 
Non-target lesion: Disappearance of all non-target lesions. All lymph nodes must be 
non-pathological in size (<10 mm short axis). 
 
Partial Response (PR): 
Target lesion: At least a 30% decrease in the sum of diameters of target lesions, 
taking as reference the baseline sum diameters. 
 
Non-target lesion: Not applicable  


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 Protocol Number:  LCI-LUN-ABR-001
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Stable Disease (SD): 
Target lesion: Neither sufficient shrinkage to qualify for a partial response, nor 
sufficient increase to qualify for progressive disease, taking as reference the 
smallest sum diameters while on study. 
 
Non-target lesion: Not applicable.  
 
Progressive Disease (PD): 
Target lesion: At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that 
is the smallest on study). In addition to the relative increase of 20%, the sum must 
also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of 
one or more new lesions is also considered progression). 
 
Non-target lesion: Unequivocal progression (as described in RECIST version 1.1) 
of existing non-target lesions. (Note: the appearance of one or more new lesions is 
also considered progression). 
 
Non-Complete Response / Non-Progressive Disease:  
 
Target lesion: Not applicable 
 
Non-target lesion: Persistence of one or more non-target lesion(s). 
 
 
 


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 Protocol Number:  LCI-LUN-ABR-001
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Table 12.1.1: Summary of RECIST 
 
Target 
Lesions 
Non-target Lesions 
New Lesions 
Overall 
Response 
Best Response for this 
Category also requires 
CR 
CR 
No 
CR 
Documented at least once 
4 weeks from baseline 
CR 
Non-CR/Non-PD 
No 
PR 
Documented at least once 
PR 
Non-PD 
No 
PR 
4 weeks from baseline 
SD 
Non-PD 
No 
SD 
Documented at least once 
4 weeks from baseline 
PD 
Any 
Yes or No 
PD 
No prior SD, PR or CR 
Any 
PD* 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
* In  exceptional  circumstances,  unequivocal  progression  in  non-target  lesions  may  be  accepted  as  disease 
progression. 
 
If nodal disease is included in the sum of target lesions and the nodes decrease to 
‘normal’ size (<10 mm), a measurement may still be reported on scans. The 
measurement should be recorded even though the nodes are normal in order not to 
overstate progression should it be based on increase in size of the nodes. This 
means that subjects with CR may not have a total sum of the diameters of ‘zero’. 
 
Subjects with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be 
reported as ‘symptomatic deterioration’. Every effort should be made to document 
objective progression even after discontinuation of treatment. Symptomatic 
deterioration is not a descriptor of an objective response: it is a reason for stopping 
study therapy. It is included as part of the criteria for determination of Progression 
Free Survival.  The objective response status of such subjects is to be determined by 
evaluation of target and non-target disease. 
 
For equivocal findings of progression (e.g. very small and uncertain new lesions; 
cystic changes or necrosis in existing lesions), treatment may continue until the next 
scheduled assessment. If at the next scheduled assessment, progression is 
confirmed, the date of progression should be the earlier date when progression was 
suspected. 
 
13. 
STATISTICAL DESIGN 
 
13.1. Sample Size Determination 
 
The primary objective of this study is to assess the efficacy in terms of overall 
tumor response of the combination of carboplatin with nab-paclitaxel in subjects 
with advanced squamous cell lung cancer.  Subjects will receive six 3-week cycles 


42 
 Protocol Number:  LCI-LUN-ABR-001
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
of treatment.  The primary endpoint of this study is a binary variable determined for 
each patient indicating whether or not they achieved an overall tumor response 
(defined as either CR or PR). 
 
A Bayesian design based on predictive probability will be implemented. This 
design allows for early stopping if data indicates that the treatment is ineffective. 
The stopping boundary is chosen by computing the predictive probability from 
observed data.  Specifically, the trial will stop if the current data indicates that, by 
the end of the trial, it is highly unlikely the 6-cycle best response rate in treated 
subjects to be higher than 0.20. The specific description of the methodology is 
given below. Early treatment discontinuation due to unacceptable toxicity, PD 
(including clinical progression) or death will be considered as failures. Other 
subjects not meeting all of the criteria for being included in the efficacy population 
(Section 13.3) will be considered as in-evaluable and therefore will not contribute to 
the sample size of evaluable subjects. 
 
The maximum number of evaluable subjects is N=45.  The treatment outcomes will 
be monitored at cohorts of 15, 30 and 45 subjects.  If X responses (CR or PR) have 
been observed in the first n subjects and Y represents possible number of responses 
in the next (N-n) subjects, the predictive probability (PP) of concluding a positive 
result by the end of the trial is defined as: 
 
N n 
PP = 
i0 
{Prob(Y=i) [Prob (response rate > 0.20 | X, N, Y=i) > P 
 
 
T]}. 


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 Protocol Number:  LCI-LUN-ABR-001
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The trial will be stopped early if PP < PL, where PT and PL are the parameters to 
be determined to yield desirable operating characteristics.  The assumption is that 
the number of subjects that achieve best response of CR or PR follows a binomial 
distribution with a probability of p, and p has a prior distribution of Beta (0.2, 0.8).  
In addition, the probability of accepting the new treatment be no larger than 
0.10 when the true best response rate is 0.20. A search algorithm is implemented to 
find that PT =0.91 and PL =0.04 satisfy the constraint and at the same time 
minimize the expected sample size when the true best response rate is 0.20. 
 
The following table lists the cumulative number of subjects (n) and the rejection 
region in the number of best responses of CR or PR in n subjects. The trial will be 
stopped and the treatment will be considered ineffective when the number of 
responses first falls into the rejection region. 
 
Table 13.1.1: Rejection Region 
N 
Rejection Region in Number of 
Responses (CR or PR) 
15 
0 – 2 
30 
3 – 6 
45 
7-12 
 
From a frequentist perspective, the statistical operating characteristics of the trial 
are given as follows. Assuming the true overall response rate is 0.20 under the 
null hypothesis (i.e. the trial is ineffective), then this design will provide 81% 
power to detect a difference of 0.15, or a true best response rate is 0.35 under the 
alternative hypothesis, assuming an alpha = 0.09 significance level.  The 
probabilities of terminating the trial early assuming the true best response rate is 
0.20 are 0.40 and 0.65 after Stage 1 and Stage 2, respectively. 
 
To account for about 10% of enrolled patients not meeting the criteria to be 
included in the efficacy population, we will accrue about 50 subjects. 
 
13.2. Analysis Endpoints 
 
13.2.1. Primary Efficacy Endpoint 
 
The primary endpoint is a binary variable determined for each patient indicating 
whether or not they achieved a CR or PR as defined in Section 
12.1.4. As per RECIST 1.1, because overall response is the primary endpoint for 
this study, best responses of CR or PR must be confirmed by a subsequent 
radiologic assessment. 
 
 


44 
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Disease control 
Disease control is calculated for each subject 
indicating whether or not they achieved an overall 
response of stable disease or better. 
Duration of response 
For subjects who achieve a CR or PR, response 
duration will be measured from the first day of the 
response until the day on which progressive disease 
(PD) or death occurred. The censoring method will be 
the same as that described for PFS. 
Duration of disease 
control 
For subjects who achieve SD or better, duration of 
disease control will be measured from the treatment 
start date until the day on which progressive 
disease (PD) or death occurred. The censoring 
method will be the same as that described for PFS. 
Progress-free survival 
(PFS) 
PFS is defined as the duration of time from treatment 
start date to time of progression or death.  Disease 
progression may be determined objectively as 
13.2.2. Secondary Efficacy Endpoints 
Table 13.2.1: Efficacy Endpoint Definitions 
 


45 
 Protocol Number:  LCI-LUN-ABR-001
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in Section 12.1.4 or subjectively as determined by the 
investigator.  Evidence for subjective progressions must 
be documented in the medical records.  For objective 
disease progression, the date of PD is the date of the 
radiologic assessment that identified RECIST-defined 
progressive disease. For subjective disease progression, 
the date of PD is the date that the clinician makes the 
determination of disease progression. If the subject died 
without documented disease progression, the date of 
progression will be the date of death. For surviving 
subjects who do not have objectively documented 
disease progression, PFS will be censored at the date of 
last radiologic assessment.  For subjects who receive 
subsequent anti-cancer therapy prior to documented 
disease progression, PFS will be censored at the date of 
last radiologic assessment prior to the commencement of 
subsequent therapy.  Subjects who experience an initial 
PFS event immediately following 2 or more consecutive 
missed assessments will be censored at the date of the last 
assessment prior to  those  missed assessments. For 
participants with only one missed assessment, the 
documented progressive disease status and assessment date 
will be used. 
Overall survival (OS) 
OS is defined as the duration of time from treatment 
start date to the date of death from any cause.  Subjects 
who are alive or lost to follow-up at the time of the 
analysis will be censored at the last known date they 
were alive. 
 
 
13.2.3. Safety Endpoints 
 
Safety endpoints will include data for treatment administration, adverse events (AEs), 
serious adverse events (SAEs), deaths during study treatment, and laboratory 
determinations. AEs and SAEs will be assessed according to CTCAE v4.0. 
 
13.3. Analysis Populations 
 
The efficacy population (or evaluable population) is defined as all subjects who have 
measurable disease present at baseline, have received at least one dose of study therapy, 
and have had their disease re-evaluated (either clinically or radiographically).  The 


46 
 Protocol Number:  LCI-LUN-ABR-001
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efficacy population will be used to analyze the primary and secondary efficacy 
endpoints. 
 
The safety population is defined as all subjects who have received at least one cycle of 
therapy and will be used to analyze the safety endpoints. 
 
13.4. Timing of Analysis 
 
The first interim futility analysis will occur after the overall response status has been 
determined for 15 evaluable patients, and then a second interim futility analysis will 
occur for 30 evaluable patients, given that the study is not stopped after Stage 1 for 
futility. The primary analysis will be conducted after the overall response has been 
determined for all 45 evaluable patients, given the study is not stopped after Stage 2 
futility analyses. An updated analysis will be conducted after the overall PFS censoring 
rate reaches 30% or after all surviving patients have at least one year of follow up. A 
final analysis will be conducted after the overall survival censoring rate reaches 30% or 
after all surviving patients have at least 3 years of follow up. 
 
 
13.5. Analysis Plan 
 
For the purposes of the primary analysis, the frequency and proportion of responders 
(those who achieve CR or PR) will be calculated after the best overall response has 
been determined for all patients enrolled in the efficacy population.  A corresponding 
95% confidence interval will be estimated using the Clopper Pearson method. 
Hypothesis testing will be done using the rejection regions described in Section 13.1, 
testing the null hypothesis that the ORR is less than 20%. Given the study is not 
stopped early for futility with the interim analyses at 15 and 30 subjects, if there are at 
least 13 responders in 45 evaluable subjects, the null hypothesis can be rejected.  
For the purposes of the secondary analyses, the frequency and proportion of subjects 
achieving disease control (SD, PR, or CR) will also be calculated along with 
corresponding 95% Clopper Pearson interval.  For both best response rate, and disease 
control rate, the correlation with baseline subject and disease characteristics and 
biomarkers will be evaluated using logistic regression. 
Time-to-event variables will be analyzed using survival analysis methods. Survival 
rates will be estimated using Kaplan-Meier techniques. The correlation with baseline 
subject and disease characteristics, and biomarkers will be assessed using Cox multiple 
regression models. 
The logistic regression and Cox proportional hazards models described above will 
involve univariate models to identify individual predictive markers and multivariate 
models (including backward elimination and forward selection) to identify independent 
predictive markers. 
Biomarkers in both tissue and blood will be analyzed.  Correlation among biomarkers in 
tissue, blood and between tissue and blood will be assessed.  The association among 
various continuous and discrete biomarkers will be assessed first by the exploratory data 


47 
 Protocol Number:  LCI-LUN-ABR-001
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analysis using graphical techniques such as the scatter plot matrix, box plots, and BliP 
plot17. Correlation among continuous biomarkers will be examined by Pearson or 
Spearman rank correlation coefficients.   The association on discrete biomarkers will be 
tested by Fisher’s exact test. 
 
 
14. 
DRUG DISTRIBUTION 
 
 
14.1. Supply and Dispensing 
 
ABRAXANE and carboplatin are commercially available and will be locally sourced, 
prepared, and dispensed per institutional standards. Storage and handling will comply 
with the respective package inserts. 
 
14.2. Drug Accountability 
 
All study medications will be stored at the investigational site in accordance with Good 
Clinical Practice (GCP) and Good Manufacturing Practices (GMP) requirements and 
will be inaccessible to unauthorized personnel. 
An adequate record of the dispensing of study drug, and the return of all unused study 
drugs must be kept in the form of a Drug Accountability Form. The Sponsor-
Investigator, or responsible party designated by the Sponsor-Investigator, will maintain 
a careful record of the inventory using the Drug Accountability Form. 
 
15. 
STUDY COMPLETION 
 
15.1. Completion 
 
The study will be considered complete when one or more of the following conditions is 
met: 
• 
All subjects have completed all study visits including follow-up. 
• 
All subjects have discontinued from the study. 
• The IRB, Celgene Corporation, LCI DSMC, or Sponsor-Investigator discontinues the 
study because of safety considerations. 
• The Sponsor-Investigator defines an administrative or clinical cut-off date. 
 
15.2. Termination 
The study will be terminated when one or more of the following conditions occur:  
• 
If the risk-benefit ratio becomes unacceptable owing to, for example: 
• 
Safety findings from this study (e.g. SAEs) 
• 
Results of any interim analysis 
• 
Results of parallel clinical studies 


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 Protocol Number:  LCI-LUN-ABR-001
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• 
Results of parallel animal studies (e.g. toxicity, teratogenicity, carcinogenicity, 
or reproduction toxicity) 
• 
If the study conduct (e.g. recruitment rate; dropout rate; data quality; protocol 
compliance) does not suggest a proper completion of the trial within a 
reasonable time frame 
 
The Sponsor-Investigator has the right to close the trial at any time. For any of the 
above closures, the following apply: 
 
 
• Closures should occur only after consultation between involved 
parties. 
• All affected institutions must be informed as applicable according to 
local law. 
• In case of a partial study closure, ongoing subjects, including those in 
follow-up, must be cared for in an ethical manner. 
 
Details for individual subject withdrawals can be found in Section 5.3. 
 
16. 
RETENTION OF RECORDS 
 
Documentation of adverse events, records of study drug receipt and dispensation, and 
all IRB correspondence should be retained for at least 2 years after the investigation is 
completed. 
 
17. 
ETHICAL AND LEGAL ISSUES 
 
17.1. Ethical and Legal Conduct of the Study 
 
The procedures set out in this protocol, pertaining to the conduct, evaluation, and 
documentation of this study, are designed to ensure that the Investigator abide by Good 
Clinical Practice (GCP) guidelines and under the guiding principles detailed in the Declaration 
of Helsinki. The study will also be carried out in keeping with applicable local law(s) and 
regulation(s). 
Documented approval from appropriate agencies (e.g. DSMC, IRB) will be obtained for all 
participating centers before start of the study, according to GCP, local laws, regulations and 
organizations. 
Strict adherence to all specifications laid down in this protocol is required for all aspects of 
study conduct; the Investigators may not modify or alter the procedures described in this 
protocol. 
Modifications to the study protocol will not be implemented by the Sponsor- Investigator 
without discussion and agreement by Celgene. However, the Investigators may implement a 
deviation from, or a change of, the protocol to eliminate an immediate hazard(s) to the trial 
subjects without prior approval from applicable agencies.  As soon as possible, the 
implemented deviation or change, the reasons for it and if appropriate the proposed protocol 
amendment should be submitted to the appropriate agencies.  Any deviations from the 


49 
 Protocol Number:  LCI-LUN-ABR-001
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protocol must be explained and documented by the Investigator. 
The Sponsor-Investigator is responsible for the conduct of the clinical trial at the sites in 
accordance with Title 21 of the Code of Federal Regulations and/or the Declaration of Helsinki.  
The Sponsor-Investigator is responsible for personally overseeing the treatment of all study 
subjects. The Sponsor-Investigator must assure that all study site personnel, including sub-
investigators and other study staff  members, adhere to the study protocol and all applicable 
regulations and guidelines regarding clinical trials both during and after study completion. 
The Sponsor-Investigator will be responsible for assuring that all the required data will 
be collected and properly documented. 
 
 
17.2. 
Confidentiality 
 
 
All records identifying the subject will be kept confidential and, to the extent permitted 
by the applicable laws and/or regulations, will not be made publicly available. 
 
18. 
PUBLICATION POLICY 
 
The Sponsor-Investigator must send a draft manuscript of the publication or abstract to 
Celgene Corporation prior to submission of the final version for publication or 
presentation. All relevant aspects regarding data reporting and publication will be part 
of the contract between Celgene Corporation and the Sponsor-Investigator. 
 
The Sponsor-Investigator will ensure that the information regarding the study be 
publicly available on the internet at www.clinicaltrials.gov. 


50 
 Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
REFERENCES 
 
1. 
Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: The impact of 
eliminating socioeconomic and racial disparities on premature cancer deaths. CA: Cancer 
J Clin 2011;61:212-36. 
2. 
Morgensztern D, Waqar S, Subramanian J, Gao F, Govindan R. Improving survival for 
stage IV non-small cell lung cancer: a surveillance, epidemiology, and end results survey 
from 1990 to 2005. J Thorac Oncol 2009;4:1524-9. 
3. 
Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens 
for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92-8. 
4. 
Ibrahim NK, Desai N, Legha S, et al. Phase I and pharmacokinetic study of ABI-007, a 
Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer 
Res 2002;8:1038-44. 
5. 
Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin- 
bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with 
breast cancer. J Clin Oncol 2005;23:7794-803. 
6. 
Nyman DW, Campbell KJ, Hersh E, et al. Phase I and pharmacokinetics trial of ABI-007, 
a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic 
malignancies. J Clin Oncol 2005;23:7785-93. 
7. 
Blum JL, Savin MA, Edelman G, et al. Phase II study of weekly albumin-bound 
paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes. Clin 
Breast Cancer 2007;7:850-6. 
8. 
Robidoux A, Buzdar AU, Quinaux E, et al. A phase II neoadjuvant trial of sequential 
nanoparticle albumin-bound paclitaxel followed by 5- 
fluorouracil/epirubicin/cyclophosphamide in locally advanced breast cancer. Clin Breast 
Cancer 2010;10:81-6. 
9. 
Rizvi NA, Riely GJ, Azzoli CG, et al. Phase I/II trial of weekly intravenous 130-nm 
albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell 
lung cancer. J Clin Oncol 2008;26:639-43. 
10. 
Socinski MA, Manikhas GM, Stroyakovsky DL, et al. A dose finding study of weekly 
and every-3-week nab-Paclitaxel followed by carboplatin as first-line therapy in patients 
with advanced non-small cell lung cancer. J Thorac Oncol 2010;5:852-61. 
11. 
Socinski MA, Bondarenko IN, Karaseva NA, et al. Survival results of a randomized, 
phase III trial of nab-paclitaxel and carboplatin compared with cremophor-based 
paclitaxel and carboplatin as first-line therapy in advanced non-small cell lung cancer. J 
Clin Oncol, 2011 ASCO Annual Meeting Proceedings 2011;29:7551. 
12. 
Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination 
with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in 
patients with advanced non-small-cell lung lancer: Final results of a phase III trial. J Clin 
Oncol 2012;30:2055-62. 
13. 
Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of 
docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non- 


51 
 Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003;21:3016-24. 
14. 
Sederholm C, Hillerdal G, Lamberg K, et al. Phase III trial of gemcitabine plus 
carboplatin versus single-agent gemcitabine in the treatment of locally advanced or 
metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin 
Oncol 2005;23:8380-8. 
15. 
ten Tije AJ, Verweij J, Loos WJ, Sparreboom A. Pharmacological effects of formulation 
vehicles : implications for cancer chemotherapy. Clin Pharmacokinet 2003;42:665-85. 
16. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. 
17. 
Lee JJ, Tu ZN. A versatile one-dimensional distribution plot: the BLiP plot. The 
American Statistician 1997;51:63-70. 
18. 
Desai N, Trieu V, Yao Z, et al: Increased Antitumor Activity, Intratumor Paclitaxel 
Concentrations and Endothelial Cell Transport of Cremophor-Free, Albumin-Bound 
Paclitaxel, ABI-007, Compared with Cremophor-Based Paclitaxel. Clin Cancer Res. 
2006; 12(4). 1317-1324. 
19. 
Chen, N., et al: Pharmacokinetics and Pharmacodynamics of Nab-paclitaxel in Patients 
with Solid Tumors: Disposition Kinetics and Pharmacology Distinct from Solvent-based 
Paclitaxel. The Journal of Clinical Pharmacology, 2014. doi: 10.1002/jcph.304. 


52 
 Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
 
APPENDICES 
 
APPENDIX A: Performance Status Criteria 
 
ECOG Performance Status Scale 
Grade 
Descriptions 
0 
Normal activity.  Fully active, able 
to carry on all pre-disease 
performance without restriction. 
1 
Symptoms, but ambulatory. 
Restricted in physically strenuous 
activity, but ambulatory and able 
to carry out work of a light or 
sedentary nature (e.g., light 
housework, office work). 
2 
In bed <50% of the time. 
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities.  Up and about 
more than 50% of waking hours. 
3 
In bed >50% of the time.  Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours. 
4 
100% bedridden.  Completely 
disabled. Cannot carry on any 
self-care.  Totally confined to bed 
or chair. 
5 
Dead. 


53 
 Protocol Number:  LCI-LUN-ABR-001
Version -2:  November 11, 2015
 
 
Required Forms 
Baseline 
During 
Treatment 
End of 
Treatment 
Follow-Up 
LCI-LUN-ABR-001: 
Registration/On Study Formg 
X 
LCI-LUN-ABR-001: Medical 
History eCRF 
X 
Template: Prior Treatment (All) 
eCRF 
X 
LCI-LUN-ABR-001: Adverse 
Events eCRF 
X 
Xa 
X 
Template: Concomitant 
Medications eCRF 
X 
Xa 
X 
Template: Radiology eCRFf 
X 
X 
X 
X 
LCI-LUN-ABR-001: Office 
Visit eCRF 
Xa 
LCI-LUN-ABR-001: Off 
Treatment eCRF 
Xb 
Template: Subsequent Treatment 
(All) eCRF 
Xe 
Template: Follow-Up eCRF 
Xc 
Template: Death eCRFd 
 
APPENDIX B: Forms Submission Schedule 
 
Complete all electronic case report forms in the CTMS within 10 business days of the visit. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Every 3 weeks, ± 7 days. 
b Within 30 days after last dose of study drug. 
c Every 6 months until death or lost to follow-up. 
d At death, regardless of time point. 
e When a subsequent anti-cancer therapy is administered. 
f Every 6 weeks during treatment, and whenever a scan is done thereafter. 
g See Appendix C for hard copy form. 


54 
Protocol Number:  LCI-LUN-ABR-001 
Version -2:  November 11, 2015 
 
 
 
 
 

ICF_001.pdf: 
Official Title:  LCI-LUN-ABR-001: A Pilot Study of Carboplatin With Nab-Paclitaxel in 
Patients With Advanced Non-Small Cell Lung Cancer of Squamous Histology 
IRB-Approved Date:  2/2/2017
NCT02328105


Levine Cancer Institute / Protocol Number LCI-LUN-ABR-001 
Page 1 of 15 
Kathryn Mileham, M.D. 
Chesapeake IRB Approved Version 2 Feb 2017 
CAROLINAS HEALTHCARE SYSTEM 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
Sponsor / Study Title: 
Levine Cancer Institute, A Pilot Study of Carboplatin with Nab-
Paclitaxel in Patients with Advanced Non-Small Cell Lung 
Cancer of Squamous Histology 
Protocol Number: 
LCI-LUN-ABR-001 
Principal Investigator: 
Kathryn Mileham, M.D. 
Telephone: 
 (24 Hours)
Address: 
Levine Cancer Institute 
 
 
INTRODUCTION 
The study doctor and study associates (the investigators) are asking you to participate in a research 
study at Levine Cancer Institute (LCI) and Carolinas HealthCare System (CHS) of a study with 
carboplatin and nab-paclitaxel in patients with advanced non-small cell lung cancer of squamous 
histology.  The purpose of this study is to see how well patients respond to this study drug 
combination.  You are being asked to take part in this study because you are a patient with advanced 
non-small cell squamous lung cancer.   
This is a clinical trial, a type of research study. Your study doctor will explain the clinical trial to you. 
Clinical trials include only people who choose to take part. Please take your time to make your 
decision about taking part. You have also been told that you have the option not to participate. You 
may discuss your decision with your friends and family. You can also discuss it with your healthcare 
team. If you have any questions, you can ask your study doctor for more explanation.  
This study is being carried out under the sponsorship of Levine Cancer Institute (LCI).  Celgene 
Corporation is the company that makes nab-paclitaxel that will be used in this study but is not 
providing the drug for this study. 
WHY IS THIS STUDY BEING DONE? 
Lung cancer is the leading cause of cancer death in the United States and worldwide. Squamous cell 
carcinoma (SCC) accounts for about 30% of new cases of lung cancer in the United States. Recent 
studies have shown improved outcomes for SCC potentially due to new treatment options for 


Levine Cancer Institute / Protocol Number LCI-LUN-ABR-001 
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Kathryn Mileham, M.D.
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cancer. Nab-paclitaxel (commercially known as Abraxane) was recently approved by the Food and 
Drug Administration (FDA) for the treatment of lung cancer in combination with carboplatin for 
newly diagnosed patients with lung cancer who are not eligible for curative surgery or radiotherapy. 
Nab-paclitaxel is thought to work by increasing the amount of paclitaxel (the active ingredient in 
nab-paclitaxel) in the tumor and also reducing the toxic effects in normal tissue.  
The primary purpose of this study is to explore this study drug combination in patients with 
advanced SCC and compare to best responses in prior studies involving patients with SCC, as well 
as determine whether there are any biomarkers (biologic characteristics) which can predict response 
to treatment. 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
You will be 1 of approximately 50 subjects enrolled on this study at Levine Cancer Institute and 
your participation will last for 6 cycles of study treatment followed by follow-up data collection for 3 
years after completion of follow-up from your enrollment date, or until you no longer wish to 
participate. 
HOW THE STUDY WORKS 
Before you begin study treatment (Baseline): 
In order to participate in this study, you will need to review, sign, and date this informed consent 
document. Following this, information about you will be obtained from your medical record to 
determine your eligibility to enroll on the study. We will collect demographic information (i.e. your 
age, race), review your medical history, perform a physical exam, and collect blood for laboratory 
tests. We will also keep a record of any medications you are taking and any existing side effects. 
An EKG to assess your heart function and a CT scan will also be required if you haven’t had one 
within the last 30 days. These tests are often routinely obtained before standard chemotherapy.  
Additionally, if you are a woman of child-bearing potential, you will have a urine or blood pregnancy 
test. 
Specimen Collection for the Purposes of Research Before you Begin Study Treatment: 
If you agree to participate in this study and have had a tumor biopsy within the past 60 days, we 
would like to analyze a portion of your previously collected biopsy specimen for tissue biomarkers.  
If the previously collected tumor tissue is unavailable or insufficient, we would like to obtain a new  
biopsy tumor sample for tissue biomarker analysis instead. You will be required to sign a separate 
procedure consent to have the biopsy procedure, which will be done before you begin treatment on 
this study. If you do not have sufficient tumor tissue from a previous biopsy or surgery, and 
you do not wish to have a new biopsy, you will not be eligible to participate in this study. 
Recent archived (previously collected tissue within the last 60 days) or fresh tissue tumor specimen is 
REQUIRED. 


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Kathryn Mileham, M.D.
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In addition to tumor biomarker analysis, we will also collect an additional tube of blood (about 1-2 
tablespoons) for blood-based biomarker analysis within 30 days of the start of study treatment and 
before your first dose of study treatment. This additional tube of blood will be drawn during a time 
when you are already having blood drawn for clinical laboratory tests. Your blood will be used to 
examine biological molecules found in blood that may signify normal or abnormal processes related 
to your cancer. If you do not wish to have this additional tube of blood drawn for blood-based 
biomarker research, you will not be eligible to participate in this study.  
All samples collected for research purposes will be labeled with a unique number instead of your 
name. If you decide later that you do not want Levine Cancer Institute to use these samples for 
research, you may request that unprocessed samples be destroyed by writing to your study doctor at 
the address listed on the first page of this consent form. 
During Study Treatment (Intervention; 6 cycles): 
During the treatment period, you will receive a chemotherapy infusion of carboplatin and nab-
paclitaxel for 6 cycles. Each cycle is 21 days long. You will have physical exams, lab work, and 
medications and side effects assessments during each cycle according to the study calendar.  
Every 6 weeks you will also have a CT scan. An additional tube of blood (about 1-2 tablespoons) 
will be collected for blood-based biomarker analysis before you receive your study treatment on 
cycles 3 and 5. The additional tube of blood will be drawn during a time when you are already 
having blood drawn for clinical laboratory tests. This additional tube of blood will be labeled with a 
unique number instead of your name. If you decide later that you do not want Levine Cancer 
Institute to use these blood samples for research, you may request that any unprocessed samples be 
destroyed by writing to your study doctor at the address listed on the first page of this form. 
Samples already processed will not be able to be destroyed and will remain part of the study data.  
After You Complete Study Treatment (Post-intervention; one visit): 
Within 30 days of your last chemotherapy infusion, you will have a physical exam, lab work, CT 
scan, and medications and side effects assessments. A tube of blood (about 2 tablespoons) will also 
be collected for blood-based biomarker analysis. 
Follow-Up: 
After you have completed the treatment period of this study, you will have doctor’s visits and CT 
scans according to routine care. We will collect information from your medical record for the 
purposes of this study to document your disease status every 6 months until you complete 3 years of 
follow-up from your enrollment date. 
RISKS 
You may have side effects while you are on this study. Everyone taking part in the study will be 
carefully watched for side effects. However, doctors don’t know all the side effects that may happen. 
Side effects can be mild or very serious. Your healthcare team may give you medicines to lessen side 


Levine Cancer Institute / Protocol Number LCI-LUN-ABR-001 
Page 4 of 15 
 
Kathryn Mileham, M.D. 
Chesapeake IRB Approved Version 2 Feb 2017 
 
 
 
 
 
 
effects. Many side effects go away after you stop taking carboplatin and nab-paclitaxel. In some 
cases, side effects can be serious in that they can be long lasting, may never go away, may result in 
hospitalization, or may result in death. 
 
You should talk to your study doctor about any side effects that you have while taking part in the 
study. 
 
Carboplatin: 
 
Likely: 
• Low white blood cell counts- this may make you more open to infection 
• Low platelet count- this may make you bruise more easily and bleed longer if injured 
• Low red blood cell count (anemia) which may cause tiredness, shortness of breath  
• Fatigue (feeling tired) 
• Loss of appetite and weight loss 
• Diarrhea 
• Constipation 
• Nausea 
• Vomiting 
• Abdominal (belly) pain 
• Skin rash 
• Changes in taste 
• Changes in electrolytes in the blood such as magnesium and potassium 
• Decrease in kidney or liver function 
• Hair loss 
 
Less Likely, but Serious: 
• Numbness or tingling in fingers or toes 
• Ringing in the ears and hearing loss 
• Allergic reactions (Some symptoms of allergic reactions are rash, wheezing and difficulty 
breathing, dizziness and fainting, swelling around the mouth, throat or eyes, a fast pulse or 
sweating. Please seek treatment immediately and tell the study doctor and study staff if you 
have any of these symptoms.) 
• Chills and fever with aches and pains 
• Sores in the mouth and throat [that can lead to difficulty swallowing and dehydration (lack of 
fluids)] 
• Altered (changed) vision 
 
Rare, but Serious: 
• Seizures 
• Secondary cancers such as acute leukemia (cancer of the blood) which may cause death 
• Kidney failure requiring dialysis (the blood is circulated outside of the body to be filtered) 
• Deafness 


Levine Cancer Institute / Protocol Number LCI-LUN-ABR-001 
Page 5 of 15 
 
Kathryn Mileham, M.D. 
Chesapeake IRB Approved Version 2 Feb 2017 
 
 
 
 
 
 
• Death  
 
Nab-Paclitaxel (Abraxane): 
 
Likely:  
• Anemia 
• Low number of white blood cells with or without fever (that may make it easier to get 
infections) 
• A decrease in the number platelets, the cells that help your blood to clot (which may lead to 
unusual bleeding or bruising under the skin) 
• Constipation 
• Diarrhea 
• Nausea 
• Vomiting 
• Stomach pain 
• Pain, swelling or sores on the inside of the mouth 
• Neuropathy, a disorder of the nerves which can cause tingling or numbness, weakness, or 
decreased sensation or movement 
• Dizziness 
• Headache 
• Feeling tired or weak 
• Pain (including muscle, joint, bone, and chest pain) 
• Swelling caused by fluid held in the tissues, especially of the ankles, feet or fingers 
• Fever 
• Chills 
• Decreased appetite 
• Change in taste 
• Weight loss 
• Difficulty sleeping 
• Depression 
• Cough 
• Shortness of breath 
• Hair loss 
• Rash, possibly red, bumpy or generalized 
• Itchiness 
• Changes in nails, including discoloration or separation from nail bed 
• Abnormal liver function test results 
• Dehydration (loss of water and minerals in the body) 
• Nose bleed 
 


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Kathryn Mileham, M.D. 
Chesapeake IRB Approved Version 2 Feb 2017 
 
 
 
 
 
 
Less Likely:  
• Bone marrow depression which is a severe reduction of red or white blood cells and platelets 
(at nearly the same time) which can cause weakness, bruising, or make infections more likely 
• Infections, including pneumonia or of the lung, mouth, gallbladder, urinary tract, nail, or hair 
follicle, (which may be bacterial, fungal or viral) 
• A very severe infection of the blood which may include a decrease in blood pressure to 
dangerous or even fatal levels 
• Inflammation of the lung passages 
• Thickening, inflammation or scarring in the lungs which may cause breathlessness, cough 
• Inflammation of the bowel causing abdominal pain or diarrhea 
• Blockage of the intestine 
• Trouble swallowing 
• Indigestion or upset stomach 
• Abnormal chemistry or electrolyte blood test results 
• Acute kidney failure (Inability to eliminate fluids or waste products from digestion)  
• Blood in the urine 
• Lack of muscle coordination 
• Muscle weakness 
• Anxiety 
• Nasal congestion 
• Mouth or throat pain 
• Dry mouth, nose and throat 
• Coughing up blood or bloody sputum 
• Blood clot in the lungs or in deep vein 
• Fluid in the chest cavity 
• Red or flushed skin 
• Dry skin 
• Hand-foot syndrome, involving reddening, swelling, numbness and peeling of palms and 
soles of feet 
• High blood pressure 
• Low blood pressure 
• Faster heart beat 
• Watery eyes 
• Changes in vision or blurry vision 
• Infusion site reactions (described as discomfort, bleeding or bruising/swelling at the needle 
site, and in some instances infection or leaking of fluid outside of blood vessel) 
• Localized swelling due to build-up of lymph fluid 
•  Acute renal failure (when your kidneys suddenly lose the ability to function) 
• Hemolytic-uremic syndrome (HUS) (the abnormal early destruction of red blood cells which 
can lead to kidney failure) 
 
 


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Kathryn Mileham, M.D. 
Chesapeake IRB Approved Version 2 Feb 2017 
 
 
 
 
 
 
Unlikely: 
• Stevens-Johnson Syndrome (SJS), a serious, potentially life threatening, skin reaction often 
with painful blistering of the skin and mucous membranes 
• Toxic epidermal necrolysis (TEN), a serious, potentially life threatening, skin reaction often 
with painful blistering of the skin and mucous membranes 
• A decrease in the heart’s ability to pump blood to all parts of the body and possibly heart 
failure (back-up of fluid in the lungs and accumulation of excess fluid in body tissues, such 
as legs and abdomen.) 
• Irregular or slow heart beat 
• Cardiac arrest (stopping of the heart) 
• Allergic reaction (may include skin inflammation, rash, trouble breathing, trouble speaking, 
fever), sometimes fatal 
• Syndrome involving abnormal blood clotting, with decreased platelets, bruising (including 
tiny red or purple spots under the skin) and possibly leading to blood clots 
• Edema/swelling and cyst formation of the macular area of the retina (the most sensitive and 
centrally-located part of the back of the inside of the eye responsible for the most detailed 
vision) 
• Irritation and redness of the thin membrane covering the eye 
• Inflammation of the cornea 
• Too much fluid in the body 
• Feeling unwell 
• Sleepiness 
• Scaly or peeling skin 
• Hives 
• A loss of nerve function in the muscles of the face 
 
Other Risks: 
 
Blood Sampling: Taking blood from a vein in your body may cause some pain, redness, or bruising 
at the injection site. In addition, lightheadedness, fainting, or an infection (rare) at the blood draw 
site is possible. If you feel faint, you should immediately lie down to avoid falling. 
 
Radiological exams (CT scans): Computed tomography scans use X-ray radiation. Radiation has 
the potential to cause cancer or harm an unborn child. The amount of radiation you will receive 
during a CT scan is very low and most doctors agree that the benefits outweigh the risks. Some CT 
scans will require you take a “contrast solution” either by mouth, through the rectum or by injection 
into a vein. You may experience discomfort from lying still in an enclosed space for a prolonged 
period of time. 
 
Although rare, the contrast solution used in CT scans may cause an allergic reaction such as nausea, 
vomiting, itching, skin rash, or in very rare instances swelling of the throat and difficulty breathing. 
If you feel any of these symptoms of an allergic reaction you must tell the clinical staff 
immediately so that you can be treated quickly.  
 


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Kathryn Mileham, M.D. 
Chesapeake IRB Approved Version 2 Feb 2017 
 
 
 
 
 
 
 
Tumor Biopsy: The risks of a biopsy can include bleeding, pain, and infection. To reduce 
these risks, the site of the biopsy will be numbed and sterile techniques will be used. You 
will sign a separate consent for this procedure. 
 
ECG (Electrocardiogram) Risks: An ECG traces the electrical activity of the heart.  You may 
have mild irritation, slight redness, or itching at the sites on your skin where the recording patches 
are placed.   
 
Reproductive Risks: If you are a woman who can get pregnant, or if you think you might be 
pregnant or might get pregnant during the study, you should not take part in this study. Nab-
paclitaxel can cause harm to an unborn child if given to a pregnant woman. You cannot take part in 
this study if you are pregnant or breast-feeding. Because of the possible risks to an unborn child, if 
you are a female who can become pregnant, you will be asked to take a pregnancy test within 72 
hours prior to starting study drug treatment.  Women who may become pregnant should use 
effective birth control (contraception) throughout the study and for 3 months after your last dose of 
study drug. Talk to your study doctor about the best way to prevent pregnancy while receiving nab-
paclitaxel. 
 
If you become pregnant during the study you must tell the study doctor right away. If this happens, 
your participation in this study will be discontinued. If you become pregnant within 3 months after 
taking your last dose of study drug you must tell the study doctor right away. The study doctor will 
follow you and your pregnancy to birth. 
 
If you are a man with a partner of childbearing age, you must agree to use a medical doctor- 
approved form of contraception throughout the study, and should avoid fathering a child for  
6 months after your last dose of study drug. If your partner becomes pregnant during the study or 
within 6 months after you took your last dose of study drug, you must tell the study doctor right 
away. Nab-paclitaxel can harm the unborn baby of your partner. Talk to your study doctor if this is a 
concern to you.  
 
EXCLUSION CRITERIA 
You may not participate in this study if any of the following are true: 
 
• You decline this consent. 
• You have received prior treatment for metastatic disease. 
• You are receiving drugs as part of another clinical trial. 
• You have a hypersensitivity to either carboplatin or nab-paclitaxel. 
• You have an uncontrolled and current illness such as an active infection, heart problems, or 
psychiatric/social issues that would limit your compliance with study requirements. 
• You are pregnant or breast feeding. 
• You have another active malignancy. 
• You have significant neuropathy (weakness, numbness, or tingling of the hands or feet). 
 
Please inform your study doctor if any of the above are true. 


Levine Cancer Institute / Protocol Number LCI-LUN-ABR-001 
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Kathryn Mileham, M.D. 
Chesapeake IRB Approved Version 2 Feb 2017 
 
 
 
 
 
 
 
BENEFITS OF STUDY TREATMENT 
 
The benefits of nab-paclitaxel in combination with carboplatin are not fully known and it might be 
that you do not gain any benefit from the study treatment. Information from this study may help 
you and/or other people with your disease in the future.  
 
ALTERNATIVE TO BEING IN THE STUDY 
 
You may choose not to participate in this study and receive routine care treatment as recommended 
by your study doctor, such as other chemotherapy or targeted therapies. Your study doctor can 
discuss the alternatives and the risks and benefits of these alternatives with you. Please ask any 
questions you may have and take as much time as you need to make your decision.  
 
COSTS AND COMPENSATION FOR PARTICIPATION IN THIS STUDY 
 
You and/or your health plan/insurance will need to pay for chemotherapy and all routine care 
procedures. There is no additional cost to you to take part in this study. LCI will pay the costs of the 
additional tissue and blood collection for biomarker analysis.  
 
You will not receive payment for taking part in this study. For more information on clinical trials 
and insurance coverage, you can visit the National Cancer Institute’s web site at 
http://cancer.gov/clinicaltrials/understanding/insurance-coverage. You can print a copy of the 
“Clinical Trials and Insurance Coverage” information from this web site.  Another way to get the 
information is to call 
 and ask them to send you a free copy.  
 
You may wish to discuss coverage with your insurance company before agreeing to participate in 
this research study. 
 
STUDY STAFF PAYMENT/FINANCIAL DISCLOSURE 
 
None of the doctors asking you to participate in this study has received or will receive money or 
other benefits for personal use from the study sponsor.  However, the sponsor will give money or 
other benefits to a research fund, foundation, educational institution, or other organization with 
which the doctor or study staff is associated. 
 
COMPENSATION FOR INJURY RESULTING FROM THE STUDY 
 
If you become ill or are hurt while you are in the study, get the medical care that you need right 
away. 
In the event that you are harmed as a result of your participation in this study, inform your study 
doctor immediately so you can access medical treatment. You and/or your health plan will be 
charged for this treatment in the usual manner. The study will not pay for standard medical 
treatment.  
 


Levine Cancer Institute / Protocol Number LCI-LUN-ABR-001 
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Kathryn Mileham, M.D. 
Chesapeake IRB Approved Version 2 Feb 2017 
 
 
 
 
 
 
You still have the right to make a claim through the legal system even if you sign this form, accept 
medical care, or accept payment for medical expenses. 
 


Levine Cancer Institute / Protocol Number LCI-LUN-ABR-001 
Page 11 of 15 
 
Kathryn Mileham, M.D. 
Chesapeake IRB Approved Version 2 Feb 2017 
 
 
 
 
 
 
 
WITHDRAWAL 
 
Your participation in this study is completely voluntary. You should feel under no pressure to be in 
the study.  If you decide not to be in the study, your decision will not in any way harm your 
relationship with your doctors or with CHS or LCI and there is no penalty or loss of benefits to you.  
You are free to stop being in the study if you change your mind after entering it.  This would not 
harm your relationship with your doctors or CHS and there is no penalty or loss of benefits to you.  
Information contributed to the study will remain in the study even if you choose to withdraw.  If 
you choose to withdraw from the study, please notify the study doctor in writing at the address listed 
on the first page of this form. 
 
Your study doctor, Levine Cancer Institute, or the FDA can remove you at any time, from this study 
without your consent for any reason, including but not limited to, the judgement that any condition 
or circumstance may jeopardize your welfare or the integrity of the study, your failure to follow 
instructions of the study doctor, or the study is stopped by Levine Cancer Institute. Your study 
doctor will explain the reasons for doing so and will help arrange for your continued care, if needed. 
 
If you leave the study for any reason you will be asked to have the procedures completed for the 
final visit. If you decide to no longer participate in the study for any reason, you have the option not 
to allow Levine Cancer Institute to use your blood and tissue samples for testing by contacting the 
study doctor at the telephone number or address listed on the first page of this form. Blood and 
tissue samples will be destroyed only if they have not already been tested.  
 
NEW INFORMATION 
 
We will tell you about new medical findings that may affect your willingness to continue in the 
study. 
 
CONFIDENTIALITY AND AUTHORIZATION TO COLLECT, USE, AND DISCLOSE 
PERSONAL MEDICAL INFORMATION 
 
The records of this study will be kept private.  In any sort of report we might publish, we will not 
include any information that will make it possible to identify a patient.  Your record for this study 
may, however, be reviewed and/or photocopied by the sponsor, by Carolinas HealthCare System, or 
by representatives of the Food and Drug Administration or other government agencies.  To that 
extent, confidentiality is not absolute. 
 
We will do our best to make sure that the personal information in your medical records will be kept 
private. However, we cannot guarantee total privacy. Your personal information may be given out if 
required by law. If information from this study is published or presented at scientific meetings, your 
name and other personal identifying information will not be used. 
 
To ensure that your information collected for this study will be kept private, your name will not be 
used whenever possible.  A code will be used instead of your name.  All of your study data will be 
kept in a secure location that is only accessible by the study doctor and research staff. 


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Organizations that may look at and/or copy your medical records for research, quality assurance, 
and data analysis include: 
 
• Carolinas HealthCare System (CHS) 
• Government agencies, like the Food and Drug Administration (FDA) that are involved in 
keeping research safe for people 
• Levine Cancer Institute 
• Chesapeake Institutional Review Board (The Institutional Review Board is a committee of 
individuals who review research studies to make sure subjects rights and safety are 
adequately considered in the way the study is designed and carried out.) 
 
The records of this study will be kept private.  In any sort of report we might publish, we will not 
include any information that will make it possible to identify a patient.  Your record for this study 
may, however, be reviewed and/or photocopied, by Carolinas HealthCare System, or by 
representatives of the Food and Drug Administration or other government agencies.  To that extent, 
confidentiality is not absolute. 
 
Information about genetic testing 
 
A Federal law called the Genetic Information Nondiscrimination Act (GINA) of 2008 generally 
makes it illegal for health insurance companies, group health plans, and most employers to 
discriminate against you based on your genetic information. This law generally will protect you in the 
following ways: 
 
• Health insurance companies and group health plans may not request your genetic 
information that we may get from this research. 
• Health insurance companies and group health plans may not use your genetic information 
when making decisions regarding your eligibility or premiums. 
• Employers with 15 or more employees may not use your genetic information that we may 
get from this research when making a decision to hire, promote, or fire you or when setting 
the terms of your employment.  
 
All health insurance companies and group health plans must follow this law. All employers with 15 
or more employees must follow this law. Be aware that this Federal law does not protect you against 
discrimination by companies that sell life insurance, disability insurance, or long term care insurance. 
 
AUTHORIZATION TO DISCLOSE HEALTH INFORMATION 
  
If you wish to take part in this clinical study, you will be asked to sign this consent form.  It allows 
the study sponsor (LCI) and study investigators to collect, process and pass on any relevant personal 
health information collected from you during the study.  These are activities routinely carried out 
during all clinical studies.  
 
You have been told that personal information about you (including sensitive personal health 
information, such as your medical history and your racial/ethnic origin if relevant to the study) will 


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Kathryn Mileham, M.D. 
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be reviewed, collected on a computer database, stored in electronic or manual files, audited, and/or 
otherwise processed by: 
 
• the clinical study sponsor-investigator, investigators and research staff  
• the study sponsor and/or its associated companies, Levine Cancer Institute 
• regulatory or other governmental authorities of the United States and other countries, 
• other persons authorized by the study sponsor, 
• Celgene Corporation, 
• Carolinas HealthCare System employees, and/or 
• other persons or agencies as required by law or allowed by federal regulations. 
 
You have been told that your personal data are being collected and processed to: 
 
• check your suitability to take part in the study, 
• monitor your study treatment with carboplatin and nab-paclitaxel, 
• compare results with those of other subjects in the study, and 
• support the development of the other study protocols.  
 
You have been told that your personal information may be processed within the U.S. or elsewhere in 
the world or transferred to or from the U.S. for review, processing and/or storage by an associated 
company or a carefully selected third-party organization.  By signing this document, you explicitly 
consent to the transfer of your personal information, including sensitive personal information, 
collected during this clinical study, for review, processing and/or storage.  Your personal health 
information may be further shared by the groups above.  If shared by them, the information will no 
longer be covered by the Privacy Rule.  However, the groups are committed to keeping your 
personal health confidential. 
 
You may refuse this authorization to transfer your personal information.  If you choose not to agree 
to this authorization, you might be ineligible to participate in the study.  If you decide not to sign 
this authorization, that will not harm your relations with your doctors or with Carolinas HealthCare 
System.   
 
You have the right to inspect your medical record at any time.  Your research record may be 
unavailable until the conclusion of the study.  At that point, it will be available.  Please speak with 
the study doctor if you desire to access your record. 
 
You have been told whenever your personal information is processed, it will be kept confidential 
and secure, to the best of our ability.  It will be used only for the purpose for which it was collected. 
 
This Authorization does not have an expiration date.  You have been told that according to the 
guidelines for good clinical practice, the study sponsor-investigator will keep your personal 
information for at least 6 years. If you do not withdraw this Authorization in writing, it will remain 
until the study is terminated.  If you wish to revoke authorization to use your personal information, 


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Kathryn Mileham, M.D. 
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you will notify the study doctor in writing at the address and telephone number listed on the first 
page of this form. 
 
Some of the data obtained from your record prior to your revocation may still be used if considered 
necessary for the study.     
 
QUESTIONS    
 
You can ask questions about this consent form or the study (before you decide to start the study or 
at any time during the study).  Questions may include: 
 
• Who to contact in the case of a research-related injury or illness. 
• Any payment for being in the study. 
• Your rights and your responsibilities as a study subject. 
• Other questions. 
 
Contact the study doctor or study staff at Carolinas HealthCare System with any questions or 
concerns.  Their telephone number is printed on the first page of this form.  If you have any 
questions or complaints about your rights as a research subject, contact:  
 
• By mail: 
Study Subject Adviser 
Chesapeake IRB 
 
 
• or call toll free: 
 
• or by email:    
 
 
 
Please reference the following number when contacting the Study Subject Adviser: Pro00010224. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the study results. You can search this Web site at any time.  
 


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CONSENT   
 
I have read this form and its contents were explained to me.  I agree to be in this research study for 
the purposes listed above.  All of my questions were answered to my satisfaction.  I will receive a 
signed and dated copy of this form for my records.  I am not giving up any of my legal rights by 
signing this form. I will receive a copy of this signed and dated form.  
 
___________________________________ 
____/____/____  _________ 
Signature of Research Subject 
 
Date 
 Time 
 
___________________________________ 
Printed Name of Research Subject 
 
STATEMENT OF PERSON EXPLAINING CONSENT  
 
I have carefully explained to the subject the nature and purpose of the above study.  There has been 
an opportunity for the subject to ask questions about this research study.  I have been available to 
answer any questions that the subject has about this study. 
 
___________________________________ 
____/____/____  _________ 
Signature of Person Explaining Consent 
Date 
 Time 
 
___________________________________ 
Printed Name of Person Explaining Consent