Clinical trial NCT01702844
Conditions: Non Small Cell Lung Cancer (NSCLC)
Keywords: Nab paclitaxel Abraxane First Line Non small cell lung cancer NSCLC Phase II Non-Randomized Elderly Lineberger UNC LCCC 1210
Sponsor: UNC Lineberger Comprehensive Cancer Center
Start date: 2013-06-25; Completion date: 2019-07-12
Enrollment: 42 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to evaluate the safety and efficacy of weekly nab-paclitaxel for a second-line treatment in elderly subjects, 70 years of age or greater, with non-small cell lung cancer (NSCLC)

Detailed description:
This will be a non-randomized phase II study evaluating the safety and efficacy of weekly nab-paclitaxel for second-line treatment in 42 elderly patients, who are 70 years of age or greater with non-small cell lung cancer (NSLC). Patients will be required to have progressed on a single prior regimen. Nab-paclitaxel 100mg/m2 will be administered intravenously, weekly for 3 weeks of every 4-week cycle. After every two cycles of therapy, imaging will be performed to assess for response. Patients will be eligible to continue receiving therapy until the time of disease progression.

Primary Objectives To evaluate the tolerability of weekly nab-paclitaxel in older adults with advanced lung cancer who have progressed on at least 1 prior regimen after 6 cycles or 3 weeks after discontinuation of treatment, for those who come off treatment earlier.

Secondary Objectives To estimate overall survival To estimate progression-free survival To estimate the response rate

Correlative Objectives To explore baseline components of the Geriatric Assessment (GA) as predictors of chemotherapy tolerance and overall survival To explore the use of p16 measurements in the elderly as predictors of chemotherapy tolerance and overall survival To explore the impact of weekly nab-paclitaxel treatment on quality of life, as measured by Lung Cancer Symptom Scale (LCSS) and Functional Assessment of Cancer Therapy-Lung (FACT-L).

Arms: arm 1: Patients will receive nab-paclitaxel once weekly for 3 weeks of every 4 week cycle
Interventions: intervention 1: Nab-Paclitaxel
Intervention descriptions: intervention 1: Administer 2 cycles of Nab-Paclitaxel 100 mg/m2 IV on days 1 8 and 15

Protocol documents:
Prot_SAP_000.pdf: 
LINEBERGER COMPREHENSIVE CANCER CENTER 
 
CLINICAL ONCOLOGY RESEARCH PROGRAM 
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
 
 
 
PROTOCOL AMENDMENT # 4 
 
 
 
LCCC 1210:  A Phase II, multicenter, single arm study of the tolerability of weekly nab-
paclitaxel as second line treatment for elderly patients with advanced lung cancer 
 
AMENDMENT INCORPORATES (check all that apply): 
       Editorial, administrative changes 
X    Scientific changes (IRB approval) 
__   Therapy changes (IRB approval) 
__ Eligibility Changes (IRB approval) 
 
 
AMENDMENT RATIONALE AND SUMMARY: 
The study has been amended to include a plan to evaluate sarcopenia by CT scans. 
 
1. New Section (1.5.4) added to explain the rationale for evaluating sarcopenia in 
this trial. 
 
2. Correlative objective (2.3.4)  added to account for sarcopenia evaluation. 
 
3. New section 6.11.6 added to efficacy assessments to account for sarcopenia 
evaluations. 
 
 
 
 
 
 
 THE ATTACHED VERSION DATED 5/26/17 INCORPORATES THE ABOVE REVISIONS 
 
 
 


LINEBERGER COMPREHENSIVE CANCER CENTER 
 
CLINICAL ONCOLOGY RESEARCH PROGRAM 
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
 
ATTACH TO THE FRONT OF EVERY COPY OF PROTOCOL 
 
 
PROTOCOL AMENDMENT # 3 
 
LCCC 1210:  A Phase II, multicenter, single arm study of the tolerability of weekly nab-
paclitaxel as second line treatment for elderly patients with advanced lung cancer 
 
AMENDMENT INCORPORATES (check all that apply): 
       Editorial, administrative changes 
X    Scientific changes (IRB approval) 
__   Therapy changes (IRB approval) 
X  Eligibility Changes (IRB approval) 
 
 
AMENDMENT RATIONALE AND SUMMARY: 
Study inclusion criteria have been revised to account for recent changes in the standard of 
care for advanced lung cancer due to the recent approval of nivolumab as second-line 
therapy for NSCLC after failure on platinum-based chemotherapy. Hence inclusion 
criterion 3.1.6 has been revised to ensure continued accrual on this study.   
 
Other changes 
The Time and Events Table (Section 6.1) has been revised to reduce the number of times 
blood is collected for analysis of p16ink4. The Time and Events Table (Section 6.1) has 
been revised so that blood collection for p16 ink4 analyses occur at screening , on cycle 3 
D1,  cycle 5 D1, and at the end of treatment rather than at screening , on Day 1 of odd 
numbered cycles, before chemotherapy beginning with cycle 3, and at the end of 
treatment. 
 
 
 
 
 
 
 
 THE ATTACHED VERSION DATED 7/24/15 INCORPORATES THE ABOVE REVISIONS 
 
ATTACH TO THE FRONT OF EVERY COPY OF PROTOCOL 
 
 
 
 


LINEBERGER COMPREHENSIVE CANCER CENTER 
 
CLINICAL ONCOLOGY RESEARCH PROGRAM 
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
 
 
 
 
PROTOCOL AMENDMENT # 2 
 
 
 
LCCC 1210:  A Phase II, multicenter, single arm study of the tolerability of weekly nab-
paclitaxel as second line treatment for elderly patients with advanced lung cancer 
 
AMENDMENT INCORPORATES (check all that apply): 
X       Editorial, administrative changes 
       Scientific changes (IRB approval) 
___ Therapy changes (IRB approval) 
X   Eligibility Changes (IRB approval) 
 
AMENDMENT RATIONALE AND SUMMARY: 
The driver for this amendment was the need to make inclusion and exclusion criteria 
consistent with regards to amount of time that should lapse between radiation therapy and 
study treatment.  As such, exclusion criterion 3.2.5 has been changed to “no radiation 
within 2 weeks’ prior to study start.” In addition, the primary endpoint (≥Grade 3 
treatment related toxicity) was slightly revised to clarify that we will focus on clinically 
significant toxicities and that those of doubtful importance, such as asymptomatic grade 3 
lymphopenia will not be included.  This change was made in sections 1.1, 2.4.1, 6.10 and 
8.1. 
 
Other changes: 
 
Deleted Appendix B. Abraxane® in Metastatic Breast Cancer, as more recent information 
is available in the package insert, which is referenced in the protocol.  
 
Section 4.4.1 clarified that D8 and D15 CBCs are not required, however, if they are done, 
the dosing table provides guidance for investigators  
 
Updated industry contact for drug shipments (section 5.1.5) 
 
Clarified in table heading that assessments listed are to occur on day 1 of every treatment 
cycle (section 6.1) Added windows (+/- 24 hours) for each study visit. 
 
Added Celgene tracking number for this study to section 7.3.4. 
 
Minor edits throughout protocol. 
 
THE ATTACHED VERSION DATED 8/21/14 INCORPORATES THE ABOVE REVISIONS 
ATTACH TO THE FRONT OF EVERY COPY OF PROTOCOL 
 
 


LINEBERGER COMPREHENSIVE CANCER CENTER 
 
CLINICAL ONCOLOGY RESEARCH PROGRAM 
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
 
 
 
PROTOCOL AMENDMENT # 1 
 
 
LCCC 1210:  A Phase II, multicenter, single arm study of the tolerability of weekly nab-
paclitaxel as second line treatment for elderly patients with advanced lung cancer 
 
 
AMENDMENT INCORPORATES (check all that apply): 
X   Editorial, administrative changes 
X   Scientific changes (IRB approval) 
___ Therapy changes (IRB approval) 
___ Eligibility Changes (IRB approval) 
 
AMENDMENT RATIONALE AND SUMMARY: 
The driver for this amendment is a change in the frequency of protocol-mandated patient 
evaluations on days 8 and 15 of each 28 day cycle.  Standard of care patient evaluation 
for NSCLC patients undergoing chemotherapy occurs on day 1 of each cycle.  As the 
primary objective of LCCC1210 is evaluation of tolerability, mandating collection of 
toxicity data on days 8 and 15 would inappropriately bias results when compared to 
historical controls.  If clinically indicated, patients will be evaluated on days 8 and 15 at 
discretion of investigator.   This change is reflected in sections 6.0 and 6.3.  
 
Other changes 
Nab-paclitaxel is now indicated (as of October 2012) for the treatment of first line 
treatment of locally advanced or metastatic NSCLC in combination with carboplatin.  
This is reflected throughout the protocol, and section 5.1.6 now includes clinical safety 
information on the use of nab-paclitaxel for this indication. 
 
The text from Section 4.3.2 (Permitted Medications) was moved to section 4.3 
(Supportive Care Guidelines); section 4.3.2 was deleted as it was redundant with section 
4.5 (Concomitant Medications/Treatments). 
 
Section 6.11.5-removed reference to required confirmation of response rate as this is 
appropriate only when primary endpoint is response. 
 
Sections 4.6, 6.11.1, 6.11.3, and 9.4 were slightly revised to match updated LCCC 
protocol template.  Section 4.9 (Study Withdrawal) was added to match updated LCCC 
protocol template.  
 
 
 
THE ATTACHED VERSION DATED 2/1913 INCORPORATES THE ABOVE REVISIONS 
ATTACH TO THE FRONT OF EVERY COPY OF PROTOCOL 
 


LINEBERGER COMPREHENSIVE CANCER CENTER 
 
CLINICAL ONCOLOGY RESEARCH PROGRAM 
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
 
LCCC 1210:  A Phase II, multicenter, single arm study of the tolerability of weekly 
nab-paclitaxel as second line treatment for elderly patients with advanced lung 
cancer 
 
Principal Investigator 
Jared Weiss, MD 
170 Manning Drive, Room 3115 
Campus box 7305 
Chapel Hill, NC   27599 
919-966-3856 (OFFICE)  
919-843-7718 (ADMIN) 
919-966-6735 (FAX) 
Email:  jared_weiss@med.unc.edu 
 
Co-Investigators 
Thomas Stinchcombe, MD 
Carrie Lee, MD, MPH 
Juneko Grilley-Olson, MD 
Hyman Muss, MD 
 
Biostatistician  
Allison Deal, MS 
Lineberger Comprehensive Cancer Center, Room 20-024 
Chapel Hill, NC 27599 
Phone: 919-966-1387 
Fax:   919-966-4244 
 
Clinical Protocol Office 
Lineberger Comprehensive Cancer Center 
The University of North Carolina at Chapel Hill 
450 West Drive, 3rd Floor, CB# 7295 
Chapel Hill, NC 27599-7295 
 
University of North Carolina Cancer Network (UNCCN) Study Coordinator: 
Phone: 919-966-7359 
Fax: 919-966-4300 
 
Sponsor:  Lineberger Comprehensive Cancer Center 
 
Funding Source: Celgene Corporation 
 
Version Date: May 26, 2017 
Revised: February 19, 2013 Amendment #1 
August 21, 2014 Amendment #2; July 24, 2015 Amendment #3, May 26, 2017 
Ammendment #4 


LINEBERGER COMPREHENSIVE CANCER CENTER 
 
CLINICAL ONCOLOGY RESEARCH PROGRAM 
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
 
LCCC  1210:  A Phase II, multicenter, single arm study of the tolerability of weekly 
nab-paclitaxel as second line treatment for elderly patients with advanced lung 
cancer 
 
 
 
Principal Investigator 
Jared Weiss, MD 
170 Manning Drive, Room 3115 
Campus box 7305 
Chapel Hill, NC   27599 
919-966-3856 (OFFICE)  
919-843-7718 (ADMIN) 
919-966-6735 (FAX) 
Email:  jared_weiss@med.unc.edu  
 
 
 
 
 
 
Signature Page 
 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable U.S. federal regulations 
and ICH guidelines. 
 
Principal Investigator (PI) Name:_______________________ 
 
PI Signature: ___________________ 
 
Date:____________________ 
 
 
 
 


LCCC 1210 
 
CONFIDENTIAL 
PI: Weiss 
 
UNIVERSITY OF NORTH CAROLINA 
 May 26, 2017 (Amendment 04)  
 
i 
TABLE OF CONTENTS 
1.0 
BACKGROUND AND RATIONALE ..................................................................1 
1.1 
Study Synopsis .................................................................................................. 1 
1.2 
Lung Cancer in the Elderly ................................................................................ 1 
1.3 
Nab-Paclitaxel (Abraxane®) ............................................................................. 3 
1.4 
Study Rationale ................................................................................................. 5 
1.5 
Correlative Studies ............................................................................................ 6 
2.0 
STUDY OBJECTIVES ...........................................................................................7 
2.1 
Primary Objective ............................................................................................. 7 
2.2 
Secondary Objectives ........................................................................................ 7 
2.3 
Correlative Objectives ....................................................................................... 7 
2.4 
Endpoints .......................................................................................................... 8 
3.0 
PATIENT ELIGIBILITY ......................................................................................8 
3.1 
Inclusion Criteria............................................................................................... 8 
3.2 
Exclusion Criteria ............................................................................................. 9 
4.0 
TREATMENT PLAN ...........................................................................................11 
4.1 
Schema ........................................................................................................... 11 
4.2 
Treatment Dosage and Administration............................................................. 11 
4.3 
Supportive Care Guidelines ............................................................................. 12 
4.4 
Toxicities and Dosing Delays/Dose Modifications .......................................... 13 
4.5 
Concomitant Medications/Treatments ............................................................. 16 
4.6 
Duration of Therapy ........................................................................................ 16 
4.7 
Duration of Follow-up ..................................................................................... 16 


LCCC 1210 
 
CONFIDENTIAL 
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UNIVERSITY OF NORTH CAROLINA 
 May 26, 2017 (Amendment 04)  
 
ii 
4.8 
Removal of Patients from Protocol Therapy .................................................... 16 
4.9 
Study Withdrawal ........................................................................................... 17 
5.0 
DRUG INFORMATION ......................................................................................17 
5.1 
Nab-paclitaxel (Abraxane®; ABI-007) ............................................................ 17 
6.0 
EVALUATIONS AND ASSESSMENTS ............................................................23 
6.1 
Time and Events Table .................................................................................... 23 
6.2 
Pre-Study Assessments .................................................................................... 25 
6.3 
Treatment Assessments ................................................................................... 25 
6.4 
End-of-Treatment Visit ................................................................................... 26 
6.5 
Follow-up........................................................................................................ 26 
6.6 
Whole blood for CBC and p16INK4a .............................................................. 27 
6.7 
Geriatric Assessment (GA) (Version 5) ........................................................... 27 
6.8 
Health Behaviors Questionnaire ...................................................................... 28 
6.9 
Assessment of Quality of Life ......................................................................... 28 
6.10 
Assessment of Safety ...................................................................................... 29 
6.11 
Assessment of Efficacy ................................................................................... 29 
7.0 
ADVERSE EVENTS ............................................................................................32 
7.1 
Definitions ...................................................................................................... 32 
7.2 
Documentation of non-serious AEs or SARs ................................................... 35 
7.3 
SAEs or Serious SARs (or Pregnancy-suspected or positive) ........................... 35 
7.4 
Data and Safety Monitoring Plan ..................................................................... 37 
8.0 
STATISTICAL CONSIDERATIONS ................................................................38 
8.1 
Study Design/Study Endpoints ........................................................................ 38 
8.2 
Sample Size and Accrual ................................................................................. 38 


LCCC 1210 
 
CONFIDENTIAL 
PI: Weiss 
 
UNIVERSITY OF NORTH CAROLINA 
 May 26, 2017 (Amendment 04)  
 
iii 
8.3 
Data Analysis Plans ......................................................................................... 39 
9.0 
STUDY MANAGEMENT ....................................................................................39 
9.1 
Institutional Review Board (IRB) Approval and Consent ................................ 39 
9.2 
Required Documentation ................................................................................. 40 
9.3 
Registration Procedures ................................................................................... 40 
9.4 
Data Management and Monitoring/Auditing.................................................... 40 
9.5 
Adherence to the Protocol ............................................................................... 41 
9.6 
Amendments to the Protocol ........................................................................... 43 
9.7 
Record Retention............................................................................................. 43 
9.8 
Obligations of Investigators ............................................................................. 44 
10.0 REFERENCES ......................................................................................................45 
11.0 APPENDIX A:  ECOG Performance Status ......................................................47 
11.1 
APPENDIX C:  Geriatric Assessment (Version 5) ........................................... 48 
11.2 
APPENDIX D:  Health Behaviors Questionnaire (Version 1) .......................... 67 
11.3 
APPENDIX E:   Lung Cancer Symptom Scale ................................................ 68 
11.4 
APPENDIX F:  Fact-L (Version 4) .................................................................. 72 


LCCC 1210 
 
CONFIDENTIAL 
PI: Weiss 
 
UNIVERSITY OF NORTH CAROLINA 
 May 26, 2017 (Amendment 04)  
 
1 
1.0 
BACKGROUND AND RATIONALE 
1.1 
Study Synopsis 
This will be a non-randomized phase II study evaluating the safety and efficacy of 
weekly nab-paclitaxel for second-line treatment in 42 elderly (≥ 70 years of age) 
patients with non-small cell lung cancer (NSCLC).  Patients will be required to 
have progressed on a single prior regimen.  Nab-paclitaxel 100mg/m2 will be 
administered intravenously, weekly for 3 weeks of every 4-week cycle.  After 
every two cycles of therapy, imaging will be performed to assess for response.  
Patients will be eligible to continue receiving therapy until the time of disease 
progression.   
 
The primary endpoint will be occurrence of clinically significant ≥Grade 3 nab-
paclitaxel-related toxicities (specifically neuropathy, myalgia, arthralgia, 
neutropenia, thrombocytopenia and anemia) as well as any ≥Grade 3 unexpected 
toxicities deemed clinically significant and considered related to nab-paclitaxel by 
the treating physician.  Secondary endpoints include overall survival; progression-
free survival; response rate; quality of life (QoL); and correlation of component 
scores of the Geriatric Assessment and p16 INK4a levels with treatment outcomes 
and toxicity. 
1.2 
Lung Cancer in the Elderly 
Lung cancer remains the leading cause of cancer mortality in the United States 
and throughout the world.[1]  The majority of patients with lung cancer will have 
NSCLC subtype, and will present with advanced stage disease.[2, 3] The goals of 
treatment for patients with advanced stage disease are to extend overall survival 
(OS), improve quality of life (QoL) and reduce disease related symptoms.  
Cytotoxic chemotherapy is the primary therapy for the majority of patients.  The 
median age of patients with advanced NSCLC in the United States is 71 years.[4]  
The number of elderly patients with advanced NSCLC is expected to increase as 
the size of the elderly population increases reflecting improvements in life 
expectancy and demographic trends.[5] 
1.2.1 First-line Treatment of the Elderly Patient with Advanced NSCLC 
A variety of subgroup analyses and population-based studies provided evidence 
that the fit elderly patient should be treated with doublet chemotherapy, but this 
remained unproven until the 2010 presentation of the Quiox study of patients aged 
70-89 with advanced NSCLC.  This phase III trial compared carboplatin monthly 
combined with weekly paclitaxel to single agent therapy (gemcitabine or 
vinorelbine); the primary end-point was OS.[6, 7] Patients assigned to the double-
agent arm experienced an improvement in progression-free (6.3 vs. 3.2 months, 
HR=0.55, p<0.001) and OS (10.4 vs. 6.2 months, HR=0.6, p = 0.0001).  Patients in 
the double agent arm compared to the single agent arm experienced a statistically 
significant higher rate of grade ≥ 3 neutropenia, febrile neutropenia, 
thrombocytopenia, and sensory neuropathy. The rate of treatment-related deaths 


LCCC 1210 
 
CONFIDENTIAL 
PI: Weiss 
 
UNIVERSITY OF NORTH CAROLINA 
 May 26, 2017 (Amendment 04)  
 
2 
was significantly higher in the double agent compared to the single agent arm 
(6.62% vs. 1.83%, p=0.035).   
1.2.2 Histology-based Therapy in First- Line Treatment 
The regimen of carboplatin plus paclitaxel has been the standard of care for first 
line chemotherapy for NSCLC for many years, regardless of age.  Other doublet 
regimens have been evaluated in NSCLC, and shown similar survival benefits to 
carboplatin/paclitaxel.  The recently published Scagliotti [8] trial was designed to 
show and confirmed non-inferiority for the combination of cisplatin plus 
pemetrexed as compared to cisplatin plus gemcitabine.  Similar to the 
carboplatin/paclitaxel doublet, median OS for both regimens was 10.3 months.  
However, based on a planned subset analysis, the combination of cisplatin plus 
pemetrexed improved OS among patients with non-squamous histology; 
conversely the combination of cisplatin plus gemcitabine was more effective in 
patients with squamous histology.  
 
Given the high tolerability and efficacy of both pemetrexed and gemcitabine, 
many clinicians consider the potential improvement of the therapeutic index with 
histology-directed therapy particularly applicable to the elderly patient.  Thus, 
many clinicians routinely treat fit elderly patients in the first line with squamous 
cell NSCLC with gemcitabine plus carboplatin and non-squamous NSCLC with 
pemetrexed plus carboplatin. 
1.2.3 Second-Line Treatment of the Elderly Patient with Advanced NSCLC 
There are currently two cytotoxic agents, pemetrexed and docetaxel, and one 
epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI: 
erlotinib) that are available for use in U.S. patients with NSCLC who have 
experienced disease progression during or after initial chemotherapy.[9-13]  No 
prospective, elderly-specific trials have been performed to define either the merits 
of second line therapy in the elderly, or choice of agent.  A limited number of 
subset analyses have been performed.  
 
A subset analysis of elderly patients (n=86, 15% of patients enrolled) in a phase 
III trial comparing docetaxel to pemetrexed was performed.  Elderly patients 
assigned to pemetrexed (n=47) compared to the docetaxel arm (n=39) 
experienced a numerically longer OS (HR=0.66, 95% CI, 0.53 to 1.42; median 
9.5 and 7.7 months, respectively).[14]  This analysis was performed before it was 
known that the efficacy of pemetrexed was restricted to tumors with non-
squamous histology and the number of elderly patients in each treatment arm was 
small. The rate of grade ≥ 3 febrile neutropenia among elderly patients was 
substantially lower in patients in the pemetrexed arm compared to the docetaxel 
arm, 2.5% and 19% (p=0.025).  While pemetrexed appeared more effective, and 
is better tolerated, most patients with non-squamous histology will have received 
pemetrexed for their first line treatment, thus reducing the choices of tolerable 
therapy for second-line. 
 


LCCC 1210 
 
CONFIDENTIAL 
PI: Weiss 
 
UNIVERSITY OF NORTH CAROLINA 
 May 26, 2017 (Amendment 04)  
 
3 
Another subset analysis was performed of elderly (≥ 70 years) patients enrolled in 
a phase III trial of erlotinib compared to placebo in patients who progressed after 
first-line chemotherapy.[15] Of the 731 patients enrolled, 163 patients were 
elderly (112 in the erlotinib arm and 51 in the placebo arm).  Elderly patients 
compared to younger patients experienced more grade 3 or 4 toxicity (35% vs. 
18%; p< 0.001), were more likely to discontinue treatment (12% vs. 3%; 
p<0.0001), and had a lower relative dose intensity (64% vs. 82% received >90% 
of the planned dose; p<0.001).  Elderly patients receiving erlotinib compared to 
placebo experienced numerically longer OS (HR=0.92; 95% CI, 0.64 to 1.34; 
p=0.67; median OS 7.6 and 5.0 months, respectively).  Therefore despite 
improved survival with erlotinib, there was a significant increase in Grade 3/4 
toxicity and increased likelihood for discontinuation of treatment.  Additional, 
more easily tolerated options are needed for second-line treatment of NSCLC in 
the elderly. 
1.3 
Nab-Paclitaxel (Abraxane®) 
The active cytotoxic agent in nanoalbumin bound paclitaxel (henceforth nab-
paclitaxel) is paclitaxel, an antimicrotubule agent that promotes the assembly of 
microtubules from tubulin dimers and stabilizes microtubules by preventing 
depolymerization.  This agent is currently indicated for the treatment of 
previously treated metastatic breast cancer, or disease that has relapsed within 6 
months of adjuvant chemotherapy. As of October 2012, this agent is also 
indicated for the treatment of locally advanced or metastatic NSCLC as first-line 
treatment in combination with carboplatin. 
 
Nab-paclitaxel delivers the paclitaxel bound to albumin and has several 
theoretical advantages over paclitaxel [16].  First, the cremophor solvent is not 
needed.  Cremophor requires special glass or non-PVC infusion systems, 
premedication with histamine 1 and 2 blockers, can cause infusion reactions and 
may contribute to peripheral neuropathy.  As albumin facilitates the 
administration of the water-insoluble compounds, effective active dose-delivery is 
higher, by as much as 49%.  Infusion time with nab-paclitaxel is faster than with 
paclitaxel.  Finally, binding of the active drug to albumin may increase tumor-
specificity. 
 
Lung cancer 
Results were recently presented from a randomized international Phase III trial 
that compared four cycles of first-line carboplatin plus paclitaxel to four cycles of 
carboplatin plus nab-paclitaxel in NSCLC.  The nab-paclitaxel arm showed 
improved response rates (RR 33%) compared to standard paclitaxel when 
combined with carboplatin (25%) [17, 18].  Importantly, most of this 
improvement was a result of improved response in patients with squamous cell 
histology, where the RR improved from 24% to 41%.  Although effective dose 
delivery was higher with nab-paclitaxel (82 mg/m2/week) compared to standard 
paclitaxel (65 mg/m2/week) the overall toxicity profile, with the exception of 
anemia and thrombocytopenia, favored nab-paclitaxel as shown in Table 1.   
 


LCCC 1210 
 
CONFIDENTIAL 
PI: Weiss 
 
UNIVERSITY OF NORTH CAROLINA 
 May 26, 2017 (Amendment 04)  
 
4 
Table 1.  Grade 3/4 toxicity following nab-paclitaxel plus carboplatin (ab-P/C) vs. paclitaxel 
plus carboplatin (P/C) in advanced NSCLC [18] 
Toxicity 
Nab-paclitaxel + 
carboplatin 
(n=514) 
% 
Paclitaxel + 
carboplatin 
(n=524) 
% 
p value 
 
Grade 3 
Grade 4 
Grade 3 
Grade 4 
 
Nonhematologic  
 
 
 
 
 
Neuropathy 
3 
0 
11 
<1 
<.001 
Myalgia 
<1 
0 
2 
0 
.011 
Arthralgia 
0 
0 
2 
0 
.008 
Hematologic 
 
 
 
 
 
Neutropenia 
33 
14 
32 
26 
<.001 
Thrombocytopenia 
13 
5 
7 
2 
<.001 
Anemia 
22 
5 
6 
<1 
<.001 
 
Exploratory subgroup analyses revealed that overall response rate (ORR) was 
improved with nab-paclitaxel in patients with squamous histology and in the 
elderly) ≥70 years old) population (Figure 1)[17, 19]. 
 
 
Figure 1.  Comparison of overall response rate (ORR) following nab-paclitaxel plus 
carboplatin (ab-P/C) vs. paclitaxel plus carboplatin (P/C) in advanced NSCLC REF. ITT = 
intent to treat analysis [17, 19] 
 
 
 
 
 
 
 
 


LCCC 1210 
 
CONFIDENTIAL 
PI: Weiss 
 
UNIVERSITY OF NORTH CAROLINA 
 May 26, 2017 (Amendment 04)  
 
5 
Overall survival results also favored the nab-paclitaxel group in the elderly 
exploratory subgroup analysis as shown in Figure 2: 
 
 
Figure 2. Comparison of overall survival following nab-paclitaxel plus carboplatin (ab-P/C) 
vs. paclitaxel plus carboplatin (P/C) in advanced NSCLC [17, 19] 
1.4 
Study Rationale 
Platinum-based doublets are the standard of care in first line with choice of 
partner drug based on patient characteristics.  For the elderly population, partner 
agents for first-line typically include gemcitabine for squamous cell NSCLC, and 
pemetrexed for non-squamous NSCLC.  Some elderly patients are treated with 
paclitaxel in combination with a platinum.   
 
The fit elderly are often not offered second-line treatment based on concern for 
toxicity.  When elderly patients with advanced NSCLC are offered second-line 
therapy, the choice of therapy is frequently based on avoidance of toxicity rather 
than on disease-related endpoints.  In particular, the one taxane that is FDA 
approved for second-line use, docetaxel, is widely considered too toxic for use in 
the elderly.   
 
We hypothesize that treatment with single-agent, weekly administration of nab-
paclitaxel will be tolerable and associated with a favorable clinical response (as 
compared to a historical control) in elderly patients undergoing second-line 
therapy for advanced NSCLC. 
 
Data suggest that weekly taxane administration improves tolerability over an 
every 3 week schedule, and does not appear to compromise clinical effectiveness.  
Taxanes have been extensively studied as weekly regimens in the breast and lung 
cancer populations.  A phase III study compared carboplatin plus paclitaxel on a 
standard every three week regimen (with both drugs given on day one) to a four 
week cycle (with carboplatin given on day 1 and paclitaxel given weekly for 
weeks one to three) [20].  Survival was similar between the two arms, but non-
hematologic toxicity favored the weekly taxane arm.  A dose finding study 
conducted at this institution showed a favorable benefit to risk ratio with weekly 


LCCC 1210 
 
CONFIDENTIAL 
PI: Weiss 
 
UNIVERSITY OF NORTH CAROLINA 
 May 26, 2017 (Amendment 04)  
 
6 
nab-paclitaxel at a dose of 100mg/m2 when administered in combination with 
carboplatin [21]. 
 
Taxanes on a weekly schedule have been shown to be particularly effective as 
first-line therapy in the elderly.  The superiority of doublet chemotherapy over 
single-agent chemotherapy in the elderly was recently demonstrated using a 
regimen of carboplatin at an AUC of 6, combined with paclitaxel at 90mg/m2 
weekly[7].  A recent phase III study compared carboplatin plus paclitaxel on an 
every three week schedule to carboplatin plus nab-paclitaxel at 100mg/m2 given 
weekly—the subgroup analysis of elderly patients was particularly favorable 
towards the weekly regimen[17].   
 
Based on these data, we propose a single arm phase II study of weekly nab-
paclitaxel in the elderly second-line NSCLC population.   Nab-paclitaxel will be 
dosed at 100mg/m2 weekly, for 3 weeks of every 4-week cycle, with cycles 
repeated until progressive disease.   
1.5 
Correlative Studies 
1.5.1 Comprehensive Geriatric Assessment 
While the Eastern Cooperative Oncology Group (ECOG) and Karnofsky 
Performance Status (PS) tools are easy and quick to use, they measure only one 
domain of functioning and thus lack sensitivity for frailty.  More comprehensive 
evaluation with a geriatric assessment (GA) tool can provide more complete 
information regarding functional status, co-morbid medical conditions, 
psychological state, social support, nutritional status, cognition, and medications.  
This information can potentially improve the therapeutic index of therapy by 
aiding in clinical selection of appropriate patients.  Comprehensive GA is well 
accepted by patients.[22]  Baseline GAs will be performed in all patients enrolled 
into this trial, and components of the GA will be explored as predictors of 
chemotherapy tolerance and overall survival. 
1.5.2 Biologic Assessment of Physiologic Age and p16INK4a 
The protein, p16INK4a, is a tumor suppressor which originates from the INK4/ARF 
locus on chromosome 9p21.  Recently, p16INK4a expression has been proposed as 
a marker of physiologic aging. Levels of p16INK4a increase nearly tenfold over 
sixty years.[23]  In addition to correlating with age, p16INK4a is associated with 
tobacco use and physical inactivity, two factors positively associated with an 
increased risk of age-related diseases.  This suggests that p16INK4a may be a 
marker not simply of chronologic age, but rather physiologic age.  In patients over 
65 years of age, treatment with chemotherapy increases p16INK4a to a similar 
extent as ten years of aging.[24]  Levels of p16INK4a will be drawn serially across 
the trial, and results explored as predictors of chemotherapy tolerance and overall 
survival.  Based on the previously reported correlation between p16INK4a and 
factors associated with age-related disease (e.g., tobacco use, physical inactivity), 
we will also include a brief health behaviors questionnaire, to capture the baseline 
level of physical activity, smoking habits and alcohol consumption.  These data 
will be used to explore correlations with changes in p16INK4a expression. 


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1.5.3 Quality of Life 
Lung Cancer Symptom Scale (LCSS)[25] 
The LCSS is designed as a site-specific measure of quality of life (QoL), 
particularly for use in clinical trials.  The LCSS is designed for use in patients 
with lung cancer, capturing QoL factors most related to treatment and changes in 
the disease state.  It evaluates six major symptoms associated with lung 
malignancies and their effect on overall symptomatic distress, functional 
activities, and global QoL.  The LCSS consists of a nine-item patient-rating scale 
and a six-item observer rating scale. 
 
Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale  
The FACT-L is a validated, multidimensional, self-report QoL instrument 
specifically designed for use with lung cancer patients [26]. It consists of 27 core 
items which assess patient function in four domains: Physical, Social/Family, 
Emotional, and Functional well-being, which is further supplemented by 9 site 
specific items to assess for lung cancer related symptoms.  Each item is rated on a 
5-point Likert type scale, and then combined to produce subscale scores for each 
domain, as well as a global QoL score.  
1.5.4 Sarcopenia assessment 
Sarcopenia has been shown to be associated with poor survival in older cancer 
patients (PMID: 26882087).  Sarcopenia, as measured by CT imaging was shown 
to predict taxane toxicity, hospitalization and survival in 40 breast cancer patients 
treated with various taxanes; a weakness of the work was heterogeneity in taxane 
treatment (PMID: 27489287). While abdominal imaging is preferred, chest CT 
has been previously used to evaluate sarcopenia in lung cancer patients (PMID: 
27364150) and it correlates with lumbar results obtained from abdominal 
imaging. 
2.0 
STUDY OBJECTIVES 
2.1 
Primary Objective 
2.1.1 To evaluate the tolerability of weekly nab-paclitaxel in older adults with advanced 
lung cancer who have progressed on at least 1 prior regimen after 6 cycles or 3 
weeks after discontinuation of treatment, for those who come off treatment 
earlier. 
2.2 
Secondary Objectives  
2.2.1 To estimate overall survival (OS)  
2.2.2 To estimate progression-free survival (PFS) 
2.2.3 To estimate the response rate (RR) 
2.3 
Correlative Objectives 


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2.3.1 To explore baseline components of the GA as predictors of chemotherapy 
tolerance and overall survival  
2.3.2 To explore the use of p16 measurements in the elderly as predictors of 
chemotherapy tolerance and overall survival  
2.3.3 To explore the impact of weekly nab-paclitaxel treatment on quality of life, as 
measured by LCSS and FACT-L 
2.3.4 To explore the impact of sarcopenia on toxicity, RR, PFS, OS and changes in 
quality of life. 
 
2.4 
Endpoints 
2.4.1 Primary Endpoint 
 Occurrence of clinically important ≥grade 3 treatment-related toxicity 
(such as neuropathy, myalgia, arthralgia, neutropenia, thrombocytopenia 
and anemia) and any ≥Grade 3 unexpected toxicities deemed clinically 
significant and considered related to nab-paclitaxel by the treating 
physician associated with  6 cycles of treatment, or 3 weeks after 
discontinuation of treatment, for those who come off treatment earlier, as 
assessed via NCI CTCAE version 4.0  
2.4.2 Secondary Endpoints 
 OS is defined as the time from day 1 (D1) of treatment until death as a 
result of any cause 
 PFS is defined as the time from D1 of treatment until progression or death 
as a result of any cause   
 OR rate (CR + PR) as defined via RECIST 1.1 
3.0 
PATIENT ELIGIBILITY 
3.1 
Inclusion Criteria 
The patient must meet all of the inclusion criteria listed below to participate in 
this study: 
3.1.1 Signed, written informed consent 
3.1.2 Male or female patient 
3.1.3  > 70 years of age 
3.1.4 Diagnosis of NSCLC, histologically or cytologically confirmed 
3.1.5 International Association for the Study of Lung Cancer (IASLC) Version 7, Stage 
IV disease; or recurrence after prior surgery or radiotherapy 
 


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3.1.6 Progression following a single line of prior cytotoxic therapy including a platinum 
agent plus a standard cytotoxic partner other than a taxane (typically pemetrexed, 
gemcitabine or vinorelbine):   
 Previous treatment with targeted therapy will not count as a prior line of 
therapy if the patient’s tumor has the relevant molecular change (eg, 
EGFR mutation for erlotinib and EML4/ALK or ROS1 for crizotinib).  
 Previous treatment with immune-oncologic agents (such as nivolumab) 
will not count as a prior line of therapy. 
3.1.7 Eastern Cooperative Oncology Group (ECOG) performance status 0 – 2; see 
Appendices, Section 11.0 
3.1.8 Adequate organ and bone marrow function as defined by: 
 Absolute neutrophil count (ANC) > 1,500 cells/mm3 
 Hemoglobin > 9 g/dL (it is acceptable to reach this through transfusion) 
 Platelets >100,000 cells/mm3 
 Creatinine  < 1.5mg/dL 
 Total bilirubin < 1.5 mg/dL 
 Alkaline phosphatase < 2.5 x upper limit of normal (ULN) 
 Alanine aminotransferase (ALT, SGPT) < 2.5 x ULN 
 Aspartate aminotransferase (AST, SGOT) < 2.5 x ULN 
3.1.9 Recovered from all reversible toxicities related to their previous treatment (other 
than alopecia) to ≤grade 1 or baseline 
3.1.10 Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE) 
3.1.11 Women of childbearing potential and sexually active men must agree to use 
effective contraception prior to study entry, for the duration of study participation 
and for three months after completing treatment.  Adequate contraception is 
defined as any medically recommended method (or combination of methods) as 
per standard of care.  
3.1.12 Negative serum or urine β-hCG pregnancy test at screening for patients of 
childbearing potential 
3.1.13 Patients with brain metastases may participate if they have undergone appropriate 
treatment for the lesion(s), are at least two weeks post treatment without evidence 
for post-treatment progression, have no significant neurologic symptoms, and no 
longer require steroids for the reason of brain metastases.  Patients with symptoms 
suggestive of CNS metastases should be evaluated with imaging prior to study 
participation. 
3.2 
Exclusion Criteria 
Subjects meeting any of the following exclusion criteria at baseline will be 
excluded from study participation:  


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3.2.1 Prior taxane therapy for any indication 
3.2.2 Less than 3 weeks elapsed since prior exposure to chemotherapy  
3.2.3 Pre-existing neuropathy greater than grade 1 
3.2.4 Other active, invasive malignancy requiring ongoing therapy or expected to 
require systemic therapy within two years; localized squamous cell carcinoma of 
the skin, basal-cell carcinoma of the skin, carcinoma in-situ of the cervix, or other 
malignancies requiring locally ablative therapy only will not result in exclusion. 
3.2.5 Concomitant anticancer therapy, immunotherapy, or radiation therapy (no 
radiation within prior 2 weeks) 
3.2.6 Have received treatment within the last 30 days prior to study entry with any drug 
that has not received regulatory approval for an indication at the time of study 
entry 
3.2.7 Uncontrolled intercurrent illness including, but not limited to, ongoing or active 
infection requiring IV antibiotics, symptomatic congestive heart failure, unstable 
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that 
would limit compliance with study requirements 
3.2.8 Pregnant women are excluded due to the potential for teratogenic or abortifacient 
effects of nab-paclitaxel.  Because there is a potential risk for adverse events in 
nursing infants secondary to treatment of the mother with these agents, 
breastfeeding should be discontinued prior to participation of the mother on study. 
3.2.9 Known hypersensitivity to protein bound paclitaxel 
3.2.10 Any other concurrent condition that in the investigator’s opinion would jeopardize 
compliance with the protocol 


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4.0 
TREATMENT PLAN 
4.1 
Schema 
 
This is a single arm, non-randomized, Phase II study evaluating the tolerability of 
weekly nab-paclitaxel as second line treatment in 42 elderly patients with 
advanced lung cancer.  Patients will receive nab-paclitaxel once weekly (days 1, 8 
and 15) for 3 weeks of every 4-week cycle.  After every 2 cycles, tumor 
measurements will be assessed for response.  Patients will continue treatment 
until disease progression.  Following discontinuation of treatment, patients will be 
followed for up to 2 years.  Section 6.0 (time and events table) outlines the study 
assessments and correlative studies, including the GA (baseline and end of 
treatment), Health Behaviors questionnaire (baseline), QoL questionnaires 
(serially across the trial), and blood levels for evaluation of p16INK4a (serially 
across the trial). See sections 6.6, 6.7, 6.8, and 6.9 for additional information on 
these correlative studies. 
 
The average duration of active patient participation in this study is expected to be 
approximately 3- 4 cycles (i.e., 3 to 4 months).  This is based on median time to 
progression of 2.9 months following second-line treatment with docetaxel in 
elderly patients with advanced NSCLC [14].  Accrual to this study is expected to 
occur within 14 months. 
4.2 
Treatment Dosage and Administration 
See Section 5.0 for more detailed information on nab-paclitaxel.  Refer to the Full 
Prescribing Information for nab-paclitaxel for complete safety information:  
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/(in addition to that already 
provided in sections 1.3, 5.0 and .  Dose modifications are described in section 
4.4.1. 
 


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Nab-paclitaxel 100mg/m2 will be infused over 30 minutes on Days 1, 8 and 15 of 
every 28-day cycle (see Table 2).  Actual body weight will be used for the dose 
calculation.  It is not a requirement to use in-line filters during the administration 
of nab-paclitaxel.  In any event, filters of pore-size less than 15 micrometers must 
not be used.  If patient body weight changes by >10%, recalculate the body 
surface area and dose of nab-paclitaxel.  Note:  Dose changes will apply for the 
next cycle; doses will not be changed mid- cycle. 
 
Nab-paclitaxel should be prepared for intravenous administration according to 
instructions provided in the manufacturers’ Prescribing Information. 
 
Table 2 
Drug 
Dose 
Route 
Schedule 
Cycle 
Length 
Nab-
paclitaxel 
100 mg/m2 
 
Intravenous 
infusion over 30 
minutes 
Days 1, 8, 15 
of each cycle 
4 weeks 
(28 days) 
 
4.3 
Supportive Care Guidelines 
All concomitant medications taken during the study will be recorded in the 
electronic case report form (eCRF) with indication, dose information, and dates of 
administration.  Subjects should receive full supportive care during the study, 
including transfusion of blood and blood products, and treatment with antibiotics, 
antiemetics, and analgesics, as appropriate. 
 
4.3.1 Nab-paclitaxel Premedication 
Patients do not require premedication prior to nab-paclitaxel administration, as 
hypersensitivity reactions are rare.  
 
Administration of solvent-based taxanes (Taxol and Taxotere) requires 
premedication with corticosteroids and histamine receptor blocking agents to 
prevent the occurrence of hypersensitivity reactions.  The solubilizing agents 
Cremophor® EL and Tween® 80 have long been implicated in adverse events 
including hypersensitivity reactions due to their detergent-like nature and known 
ability to induce histamine release. [27]  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 event of a severe hypersensitivity reaction, discontinue nab-paclitaxel. 


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4.3.2 Anti-emetic Medications 
The recommended regimen will include Zofran 16 mg by oral, or 8 mg by IV 
route, or an alternative 5HT-3 antagonist.  Aprepitant and dexamethasone use are 
not recommended as nab-paclitaxel is not sufficiently emetogenic as to require 
aprepitant and without cremophor, dexamethasone is not required to prevent 
infusion reactions.  While not recommended, neither medicine is prohibited--
clinicians may adjust the antiemetic regimen as needed for individual patients. 
4.3.3 Hematopoietic Growth Factors 
Use of erythropoiesis- stimulating agents (ESAs) will neither be recommended 
nor prohibited.  If the clinician elects to utilize ESAs, they must be used within 
FDA-approved guidelines. The use of peg-filgrastim is not allowed in this study.  
The use of prophylactic filgrastim during chemotherapy is permitted at the 
discretion of the treating physician; it is recommended in patients with low blood 
counts that threaten treatment continuity.  It is strongly advised in patients who 
have previous febrile neutropenia or who have treatment delays due to 
neutropenia. 
When filgrastim is used, administer filgrastim 5 mcg/kg/day (rounded to the 
nearest vial size per investigator/institution’s standard of care).  The number of 
days of filgrastim is up to the discretion of the treating MD; however, the patient 
must start at least 24 hours after the dose of chemotherapy and be held at least 48 
hours prior to the next dose.  The dose of filgrastim can be adjusted based on the 
investigator’s discretion. The delivery of G-CSF following week #3 of any cycle 
is per investigator discretion (since the patient will have a 2 week break prior to 
the next dose). 
4.4 
Toxicities and Dosing Delays/Dose Modifications 
Any patient who receives any treatment on this protocol will be evaluable for 
toxicity.  Each patient will be assessed periodically for the development of any 
toxicity according to the Time and Events table (Section 6.0).  Toxicity will be 
assessed according to the NCI Common Terminology Criteria for Adverse Events 
(CTCAE), version 4.0.  Dose adjustments should be made according to the system 
showing the greatest degree of toxicity.  See Section 4.4.1 for suggested dose 
modifications and dose delays due to toxicity. 
 
If more than 2 dose reductions of nab-paclitaxel are required, protocol therapy is 
to be discontinued, response assessed, and the patient should proceed to optimal 
definitive therapy outside the constraints of the clinical trial.  Once a patient’s 
dose has been reduced, the dose reduction will be permanent.  Dose re-escalation 
will not be permitted. 
 
If a patient misses more than 28 consecutive days of treatment or more than 2 
cycles of treatment due to toxicity, the patient will be removed from the study.  If 
the treating clinician feels that the patient has been benefitting from treatment 
with nab-paclitaxel and would benefit more from ongoing study therapy than 
another treatment, he/she may request an exemption from these requirements by 
the PI and these may be granted on a case-by-case basis. 


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For AEs that require dose reductions of nab-paclitaxel, please refer to the dose 
reductions described in Table 3: 
 
Table 3 
Dose Level 
Nab-paclitaxel dose (mg/m2) 
0 
(starting dose) 
100 
-1 
80 
-2 
60 
 
Hypersensitivity reactions to nab-paclitaxel rarely occur.  If they do occur, minor 
symptoms such as flushing, skin reactions, dyspnea, lower back pain, 
hypotension, or tachycardia may require temporary interruption of the infusion.  
However, severe reactions, such as hypotension requiring treatment, dyspnea 
requiring bronchodilators, angioedema or generalized urticaria require immediate 
discontinuation of nab-paclitaxel administration and aggressive symptomatic 
therapy.  Patients who experience a severe hypersensitivity reaction to nab-
paclitaxel should not be re-challenged. 
  


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4.4.1 Dose Delays and Dose Modifications for nab-paclitaxel 
Hematological Toxicity 
Toxicity grade 
Dose Level for Subsequent 
Administration 
Neutropenia or Febrile neutropenia 
 
If ANC <1,000/mm3, hold  treatment.   
 
Resume per table once ANC 
≥1,000/mm3 
Grade 2 
(ANC <1,500/mm3 to 1,000/mm3) 
Maintain dose;  Consider G-CSF 1 
Grade 3 
(ANC < 1,000/mm3) 
 1 dose level and strongly 
consider G-CSF 1 
 
Febrile neutropenia  
 
 1 dose level and administer  
G-CSF1 
Thrombocytopenia 
Day 1:  If platelets <100,000/mm3 hold 
treatment.  Initiate cycle once platelets 
≥100,000/mm3 
 
Days 8, 153:  If platelets <75,000/mm3 
hold treatment.  Resume per table once 
platelets ≥75,000/mm3 
Grade 1  
(<LLN to 75,000/mm3) 
Maintain dose.  If recurrent or 
early in treatment, ↓1 dose level 
Grade 2  
(<75,000/mm3 to 50,000/mm3) 
↓1 dose level 
(when treatment resumes) 
 
 
Grade 3 
( <50,000/mm3 to 25,000/mm3) 
↓2 dose levels 
(when treatment resumes) 
Anemia 
If Hgb<8 g/dL, transfuse PRBCs.  Once 
Hgb is > 8 g/dL, therapy may resume.  
≥Grade 3  
(Hgb <8 g/dL) 
For Hgb <8 g/dL, consider ↓1 
dose level  
(when treatment resumes) 
Non-hematological Toxicity 
Sensory neuropathy 
If ≥ grade 3, hold  treatment.  Resume 
per table once ≤grade 1 
Grade 1 
Maintain dose 
Grade 2 
↓1 dose level 
Grade 3 - 4 
↓2 dose levels  
(when treatment resumes) 
Hyperbilirubinemia 
If bilirubin >2mg/dL, hold treatment.  . 
Resume per table once bilirubin 
<2mg/dL 
Bili >2 mg/dL 
↓1 dose level  
(when treatment resumes) 
Bili >3 mg/dL 
↓2 dose levels  
(when treatment resumes) 
Transaminase elevation (ALT or AST) 
If > Grade 2 (>3 x ULN) hold 
treatments. Resume per table once 
transaminases < 3 x ULN 
Grade 1 
(>ULN – 3x ULN) 
Maintain dose 
Grade 2 
(>3 – 5 x ULN) 
↓1 dose level  
(when treatment resumes) 
≥Grade 3 
(>5 x ULN) 
↓2 dose levels 
 (when treatment resumes) 
Renal toxicity  
If serum Cr >2 mg/dL, hold treatment.  
Resume per table once serum Cr<2 
mg/dL 
≤Grade 2 
(< 3 x ULN) 
Maintain dose 
≥Grade 3 
(>3 x ULN) 
↓1 dose level 
(when treatment resumes) 
Other non-specified2 
Hold treatment until toxicity resolves to 
≤Grade 1.  Resume treatment with dose 
adjusted per table.   
≥ Grade 3 
↓1 dose level 
(when treatment resumes) 
1 If G-CSF (filgrastim) is given concurrently with weekly nab-paclitaxel, administration may begin 24 hours after nab-paclitaxel is given and 
should stop at least 48 hours prior to when nab-paclitaxel is given the following week.  The dose is 5mcg/kg/day rounded to the nearest vial 
size per investigator/institution’s standard of care.  See section 4.3.3. Note: peg-filgrastim is not permitted during the study. 
2Excludes alopecia and non-refractory nausea/vomiting 
3D8 and D15 CBCs are not required, however, if they are obtained, please follow the guidance provided in this table 
 


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4.5 
Concomitant Medications/Treatments 
No drug interactions studies have been conducted with nab-paclitaxel, a drug 
metabolized by CYP2C8 and CYP3A4.  Caution should be used when 
administering nab-paclitaxel with medications known to inhibit or induce either 
CYP2C8 or CYP3A4.  Use of peg-filgrastim (Neulasta®) is not permitted during 
this trial. 
4.6 
Duration of Therapy 
In the absence of treatment delays due to adverse events, treatment may continue 
until: 
 Disease progression 
 Inter-current illness that prevents further administration of treatment 
 Unacceptable adverse event(s) 
 Patient decides to withdraw from study treatment, OR 
 General or specific changes in the patient’s condition render the 
patient unacceptable for further treatment in the judgment of the 
investigator. 
4.7 
Duration of Follow-up 
Patients will be followed for 24 months after completion of treatment or until 
death, whichever occurs first. Patients removed from study for unacceptable 
adverse events will be followed until resolution or stabilization of the adverse 
event and followed up per protocol.   
4.8 
Removal of Patients from Protocol Therapy 
The following indications will result in discontinuation from protocol therapy 
(patient will be followed-up per protocol): 
 The investigator decides that the patient should be withdrawn from the 
study because of toxicity or other factors. If this decision is made because 
of a serious adverse event or clinically significant laboratory value, the 
study drug is to be discontinued and appropriate measures are to be taken.  
 The patient requests to be withdrawn from the study. Patient to be 
followed-up per protocol unless patient refuses 
 The patient for any reason requires treatment with another therapeutic 
agent (other than that specified by the protocol) for their disease. In this 
case discontinuation from the study occurs immediately upon introduction 
of the new agent. 
 Evidence of progressive disease  
 Unacceptable toxicity. 
 The patient becomes pregnant or fails to use adequate birth control (for 
those patients able to conceive). 
 The patient is lost to follow-up; in this case patient will be removed from 
study. 
 General or specific changes in the patient’s condition or co-morbidity 
renders the patient unacceptable for further treatment in the judgment of 
the investigator 


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If a patient is removed from study treatment, the Principal Investigator will be 
notified, and the reason for study removal and the date the patient was removed 
will be documented in the electronic Case Report Form (e-CRF).   The patient 
should be followed-up per protocol.  
4.9 
Study Withdrawal 
If a patient decides to withdraw from the study (and not just from protocol 
therapy) all efforts should be made to complete and report study assessments as 
thoroughly as possible. The investigator should contact the patient or a 
responsible relative by telephone or through a personal visit to establish as 
completely as possible the reason for the study withdrawal. A complete final 
evaluation at the time of the patient’s study withdrawal should be made with an 
explanation of why the patient is withdrawing from the study. If the reason for 
removal of a patient from the study is an adverse event, the principal specific 
event will be recorded on the eCRF. 
 
5.0 
DRUG INFORMATION 
5.1 
Nab-paclitaxel (Abraxane®; ABI-007) 
Nab-paclitaxel is a protein-bound form of paclitaxel indicated in the United States 
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.  
It is also indicated for locally advanced or metastatic NSCLC as first-line 
treatment in combination with carboplatin in patients who are not candidates for 
curative surgery or radiation therapy.  See: 
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ 
for additional information, and the nab-paclitaxel investigator’s brochure for 
complete information.   
 
5.1.1 Packaging, Labeling, Storage and Supply of nab-paclitaxel  
Nab-paclitaxel (Abraxane®) will be supplied by Celgene Corporation, in single-
use vials.  Each single-use 50 mL vial will contain paclitaxel (100 mg) and human 
albumin (HA; approximately 900 mg).  Commercial drug will be supplied.  Each 
milliliter (mL) of reconstituted suspension contains 5 mg paclitaxel.  Un-
reconstituted nab-paclitaxel (Abraxane®) should be stored at controlled room 
temperature (20 to 25C or 68 to 77F) in its original carton to protect from 
bright light.  Unopened vials are stable until the date indicated on the package 
when stored between 20°C to 25°C (68°F to 77°F), in the original package.  
Neither freezing nor refrigeration adversely affects the stability of the product. 
 
Reconstituted nab-paclitaxel (Abraxane®) should be used immediately.  If not 
used immediately, the vial of reconstituted nab-paclitaxel (Abraxane®) must be 
placed in its carton in a refrigerator at 2 to 8C (36 to 46F) for a maximum of 8 


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hours.  If not used immediately, each vial of reconstituted suspension should be 
replaced in the original carton to protect it from bright light.  Discard any unused 
portion.  Both forms should be stored in an area free of environmental extremes 
and must be accessible only to study personnel.  
 
Temperature records for nab-paclitaxel (Abraxane®) must be kept for verification 
of proper study drug storage. 
 
If storing reconstituted nab-paclitaxel (Abraxane®), some settling may occur. 
Ensure complete re-suspension by mild agitation prior to use. 
 
The suspension for infusion prepared as recommended in an infusion bag should 
be used immediately, but may be stored at ambient temperature (approximately 
25°C) and lighting conditions for up to 4 hours.   
5.1.2 Reconstitution of nab-paclitaxel 
Nab-paclitaxel will be reconstituted by appropriate study personnel and 
administered to the patient in the study site setting at weekly intervals.  The 
investigator will calculate the body surface area (BSA) of the patient in order to 
determine the total amount of nab-paclitaxel to be administered. 
 
Reconstitution and use of nab-paclitaxel: 
1. Calculate the patient’s body surface area at the beginning of the study and 
if the weight changes by >10%.  
2. Calculate the total dose (in mg) to be administered by:  
Total Dose (mg) = BSA x (study dose mg/m2) 
3. 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 vials would 
be reconstituted).  
4. Using sterile technique, prepare the vials for reconstitution. 
5. Swab the rubber stoppers with alcohol. 
6. Reconstitute each nab-paclitaxel (Abraxane®) vial by injecting 20 mL of 
0.9% Sodium Chloride Injection, USP or equivalent into each vial over a 
period of not less than 1 minute (Note: change the syringes after 
reconstituting every 3 vials).  
 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 


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of 5 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. 
7. Calculate the exact total dosing volume of 5 mg/mL suspension required 
for the patient:  Dosing volume (mL) = total dose (mg)/5 (mg/mL) 
8. The reconstituted sample should be milky and homogeneous 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.  
9. 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. 
10. 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. 
11. 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. 
5.1.3 Dose and Schedule of nab-paclitaxel 
See section 4.2. 
5.1.4 Administration 
Nab-paclitaxel will be infused intravenously over 30 minutes. Actual body weight 
will be used for the calculation.   
 
NOTE: It is not a requirement to use filter needles in the preparation of, or in-line 
filters during the administration of nab-paclitaxel. In any event, filters of pore-size 
less than 15 micrometers must not be used. 
5.1.5 Receipt and Return of nab-paclitaxel 
Upon receipt of the study drug supplies from Celgene Corporation  
Celgene Corporation 
86 Morris Avenue 
Summit, NJ  07901 
 
The investigator or designee will conduct an inventory and sign both copies of the 
study drug receipt form and forward one copy to the address indicated on the 


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form. One copy of the receipt and the packing slip must be retained in the 
investigational drug services (IDS) records. 
 
No supplies will be shipped to any site until regulatory approval has been 
obtained.  Investigational sites will be supplied with Abraxane® upon 
identification and screening of a potential trial subject. Upon identification of a 
potential subject, sites must fax a completed Drug Request Form to Celgene 
Corporation.  Allow at least 5 working days for drug shipment.  There are no 
shipments on Fridays or holidays. For re-supply of drug, please complete and fax 
the Drug Request Form to Celgene Corporation at 908-673-2779. 
 
Industry Contact: 
Martha Kennedy 
Senior Manager, Medical Operations 
Celgene Corporation 
86 Morris Avenue 
Summit, NJ  07901 
Mobile: 908-723-6919 
Fax: 908-673-2779 
Email: mkennedy@celgene.com 
 
If the investigational site does not have a policy, procedure or SOP detailing the 
process to follow for study drug destruction, the study drug must then be returned 
to Celgene using the Drug Return Form provided in the package containing the 
study drug. The following information must be recorded on the site’s pharmacy 
drug accountability log: quantity of vials to be returned, expiration date and lot 
number. A copy of the Drug Return Form and the study drug should be returned 
to Celgene Clinical Supplies Dept. using the mailing address on the packaging 
slip that came with the original study drug order. A copy of the Drug Return Form 
should be retained at the clinical site. In the event of study completion or 
termination, a copy of all pharmacy records (drug dispensing log, drug 
accountability log and any destruction memos) must be mailed to Celgene 
Medical Operations. 
 
If the investigational site has a policy, procedure or SOP detailing the process to 
follow for study drug destruction, the pharmacist or designee can choose to 
destroy the study drug on site. The following information must be recorded on the 
site’s pharmacy drug accountability log: quantity of vials destroyed, expiration 
date and lot number. The pharmacist must document that the study drug was 
destroyed in accordance with their institution’s drug destruction policy or SOP. A 
drug destruction memo and the site’s drug destruction SOP/policy should be sent 
to Celgene Medical Operations Dept. A copy of the drug destruction memo 
should be retained at the clinical site. In the event of study completion or 
termination, a copy of all pharmacy records (drug dispensing log, drug 
accountability log and any destruction memos) must be mailed to Celgene 
Medical Operations. 


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5.1.6 Clinical Safety Summary 
See prescribing information for information on nab-paclitaxel when used 
according to its FDA indication in the treatment of metastatic breast cancer and 
dosed every 3 weeks or when used in NSCLC dosed days 1, 8 and 15 of every 21 
day cycle in combination with carboplatin on day 1: 
http://www.accessdata.fda.gov/scripts/cder/drugsatfda  
 
When used in combination with carboplatin in NSCLC, the most common 
reactions (≥10%) included anemia (98%), neutropenia (85%), thrombocytopenia 
(68%), alopecia (56%), peripheral neuropathy (48%), nausea (27%), fatigue 
(25%), decreased appetite (17%), asthenia (16%), constipation (16%), diarrhea 
(15%), vomiting (12%), dyspnea (12%), peripheral edema (10%), arthralgia 
(13%), rash (10%), and myalgia (10%). 
 
When administered weekly as a single agent at 100mg/m2 in 65 patients with 
locally advanced breast cancer for 12 doses, no grade 4 nab-paclitaxel adverse 
events were reported.  The most common (% of patients) nab-paclitaxel-related 
adverse events included neutropenia (grade 2: 6%, grade 3: 3%), febrile 
neutropenia (grade 3: 2%), fatigue (grade 2: 26%, grade 3:6%) neuropathy (grade 
2: 11%, grade 3: 5%), nausea (grade 2: 10%), vomiting (grade 2: 8% , grade 3: 
2%), and diarrhea (grade 2: 9%, grade 3: 5%). Dose reductions or omissions were 
required in 14 (2%) of doses [28].   
 
The following adverse events are associated with nab-paclitaxel when studied in 
metastatic breast cancer: 
 
Hematologic:  Myelosuppression, primarily neutropenia, is dose dependent and 
reversible, but dose limiting.  Thrombocytopenia is uncommon, while anemia 
occurred in 33% (severe in <1%) of patients in the randomized trial.     
 
Infections:  Infectious episodes were reported in 24% of patients in the 
randomized phase III trial in metastatic breast cancer.   
 
Hypersensitivity: Hypersensitivity reactions (Grade 1 or 2) occurred on the day of 
nab-paclitaxel administration in the randomized phase III trial in metastatic breast 
cancer and consisted of dyspnea (1%) and flushing, hypotension, chest pain, and 
arrhythmias (all <1%).   
 
Cardiovascular:  Hypotension occurred in 5% and bradycardia (during the 
infusion) in <1% of patients in the randomized Phase III trial.  Severe 
cardiovascular events possibly related to nab-paclitaxel occurred in approximately 
3%, and included cardiac ischemia/infarction, chest pain, cardiac arrest, 
supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, 
pulmonary emboli, and hypertension.  Strokes and TIAs have been reported. 
 
ECG abnormalities: occurred in 35% of patients who had a normal ECG at 
baseline in the randomized Phase III trial in metastatic breast cancer. 


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Respiratory:  Following treatment with nab-paclitaxel, dyspnea (12%), cough 
(7%) and pneumothorax (<1%) were reported in the randomized Phase III trial in 
metastatic breast cancer.   
 
Neurologic: Sensory neuropathy occurs frequently with nab-paclitaxel (71% in 
the randomized clinical trial, 10% severe).  It is dose-dependent, and increases 
with cumulative dose.   
 
Vision:  Ocular/visual disturbances occurred in 13%; 1% were severe and 
included keratitis and blurred vision.   
 
Arthralgia/Myalgia:  Symptoms occurred in 44% of patients in the randomized 
clinical trial (8% of patients experienced severe symptoms). 
 
Hepatic:  Exposure and toxicity of paclitaxel can be increased with hepatic 
impairment.  Grade 3 or 4 elevations in GGT occurred in 14% of patients in the 
randomized Phase III trial. 
 
Renal:  Elevated serum creatinine occurred in 11% (1% severe) of patients in the 
randomized Phase III trial. 
 
General Toxicity Information 
 
Drug Interactions: No drug interactions studies have been conducted with nab-
paclitaxel, a drug metabolized by CYP2C8 and CYP3A4.  Caution should be used 
when administering nab-paclitaxel with medications known to inhibit or induce 
either CYP2C8 or CYP3A4.   
 
Injection site reactions: These reactions occur infrequently with nab-paclitaxel 
and were mild in the randomized clinical trial.  
 
Use in patients with hepatic impairment: The starting dose of nab-paclitaxel 
should be reduced for patients with moderate and severe hepatic impairment.   
 
Use in pregnancy: Nab-paclitaxel is pregnancy category D.   Men should also be 
advised not to father a child while receiving treatment with nab-paclitaxel.   
 
Albumin: Nab-paclitaxel contains human albumin, and thus carries an extremely 
remote risk for transmission of viral diseases, and Creutzfeldt-Jakob Disease.   
 
Other potential risks associated with nab-paclitaxel include mucositis, 
bilirubin/liver enzyme elevations, edema, alopecia, asthenia, nail changes, 
dehydration and pyrexia.  
 
See the nab-paclitaxel prescribing information and investigator’s brochure for 
additional information on post-marketing toxicities reported with nab-paclitaxel.   


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6.0 
EVALUATIONS AND ASSESSMENTS 
6.1 
Time and Events Table 
Assessments 
Screening1 
Day 1 of every 
cycle1a 
Day 1 of odd 
numbered cycles, 
before chemotherapy 
(begin with Cycle 3) 
Day 1 of 
Cycle 3 and 
Cycle 5 
End of Treatment2 
Follow-up3 
Informed Consent 
X 
 
 
 
 
 
Medical History 
X4 
X4 
 
 
X4 
 
Physical Exam5 
X5 
X5 
 
 
X5 
 
ECOG Performance Status 
X 
X 
 
 
X 
 
Weight 
X 
X6 
 
 
X 
 
Pregnancy test (serum or urine β-hCG)  
X 
 
 
 
 
 
CBC w/differential  
X 
X8 
 
 
X7 
 
Serum chemistries8 
X 
X8 
 
 
X7 
 
Whole blood for p16INK4a 
X9 
 
 
X9 
X9 
 
Geriatric Assessment 
X 
 
 
 
X 
 
HBQ10 
X 
 
 
 
 
 
LCSS11 
X 
 
X 
 
X 
 
Fact-L12 
X 
 
X 
 
X 
 
Tumor imaging evaluation13 
X1,13 
 
X13 
 
X2,13 
X3, 13 
Concomitant medications 
X 
X 
 
 
X 
 
Toxicity assessment 
 
Continuous during study 
Survival assessment 
 
 
 
 
 
X3 
 
 
 


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1Screening evaluations to take place within 2 weeks of day 1 of study. Screening tumor imaging may take place within 4 weeks of treatment initiation. 
1aPatients may be evaluated more frequently during cycle when clinically indicated, and at investigator discretion. Each study visit should take place within 24 hours +/- of  
originally scheduled date.  
2End of treatment visit to occur 21 to 30 days after last treatment; radiographic evaluation of tumor at discretion of physician 
3Follow-up will take place every 2-3 months after end of treatment visit for 2 years or until death (whichever is first), and may be conducted via telephone.  Evaluations limited to 
survival status, any follow-up of toxicity that is necessary, and tumor evaluation at discretion of physician.   
4Complete medical history at baseline (including history of prior treatment of NSCLC); symptom-directed history thereafter  
5 Physical exam to include vital signs and height (the latter at baseline only) 
6If weight changes >10%, recalculate the body surface area for dosing of nab-paclitaxel. 
7These are necessary if last assessment was >3 weeks prior 
8Serum chemistries to include sodium, potassium, chloride, bicarbonate, BUN, serum creatinine, glucose, calcium, phosphorus, magnesium, liver function tests (LFTs; total 
bilirubin, alkaline phosphatase, AST, ALT), total protein, albumin. (NOTE: If screening labs are drawn within 7 days prior to D1, they do not need to be repeated on D1 of cycle 
1).  
9For evaluation of p16INK4a, CBC with differential must be drawn on the same day 
10 Health Behaviors Questionnaire; see section 6.8 
11Lung Cancer Symptom Scale; see section 6.9.   
12Functional Assessment of Cancer Therapy-Lung; see section 6.9 
13 To include CT of chest, abdomen and pelvis.  CNS imaging only required if felt clinically indicated by treating physician.  Imaging during study to occur within 1 week prior to 
Day 1 of odd-numbered cycles. 


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6.2 
Pre-Study Assessments 
Baseline evaluations are to be conducted within 2 weeks prior to start of protocol 
therapy.  Tumor imaging must be done within 4 weeks prior to start of therapy.  
Baseline assessments include: 
 Complete medical history and physical examination, including height 
measurement. 
 Weight 
 ECOG Performance Status; see Appendices section 11.0 
 Geriatric Assessment (Version 5); see section 6.7; Appendices, section 
11.1 
 Health Behaviors questionnaire; see section 6.8; Appendices, section 11.2 
 LCSS; see section 6.9; Appendices, section 11.3  
 FACT-L (Version 4); see section 6.9; Appendices, section 11.4 
 Pregnancy test (serum or urine β-hCG) for female patients of childbearing 
potential 
 
Laboratory evaluations: CBC with differential; serum chemistries 
(sodium, potassium, chloride, bicarbonate, BUN, serum creatinine, 
glucose, calcium, phosphorus, magnesium, liver function tests (LFTs: total 
bilirubin, alkaline phosphatase, AST, ALT), total protein, albumin)  
 Blood sample for p16INK4a (confirm drawn on same day as CBC with 
differential) ; see section 6.6. 
 Concomitant medication(s) 
 Tumor evaluation: to include CT of chest, abdomen and pelvis.  CNS 
imaging only required if felt clinically indicated by treating physician. 
 Toxicity assessment:  record any non-serious and serious AEs and assign 
appropriate toxicity grade (NCI CTCAE, Version 4).  
6.3 
Treatment Assessments 
Day 1 each chemotherapy cycle (NOTE: If screening labs* are drawn within 7 
days prior to D1, they do not need to be repeated on D1 of cycle 1; patients may 
be evaluated more frequently during cycle when clinically indicated, and at 
investigator discretion.). 
 Physical examination and limited medical history 
 Weight 
 ECOG Performance Status (see Appendices section 11.0) 
 Laboratory evaluations: CBC with differential; serum chemistries 
(sodium, potassium, chloride, bicarbonate, BUN, serum creatinine, 
glucose, calcium, phosphorus, magnesium, liver function tests (LFTs; total 
bilirubin, alkaline phosphatase, AST, ALT), total protein, albumin)  
 Concomitant medication(s) – record all medication(s) added, changed or 
discontinued. 
 Toxicity assessment:  record any non-serious and serious AEs and assign 
appropriate toxicity grade (NCI CTCAE, Version 4).   
 


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Day 1 of odd-numbered chemotherapy cycles (beginning with Cycle 3), prior to 
chemotherapy treatment 
 Tumor evaluation (to include CT of chest, abdomen and pelvis) CNS 
imaging only required if felt clinically indicated by treating physician. 
 Imaging will occur within 1 week prior to Day 1 of odd-numbered cycles; 
results to be reviewed prior to treatment on Day 1. 
 Blood sample for p16INK4a  (confirm drawn on same day as CBC with 
differential) ; see section 6.6. 
 LCSS; see section 6.9 and Appendices, section 11.3 
 FACT-L (Version 4); see section 6.9 and Appendices, section 11.4 
6.4 
End-of-Treatment Visit 
This visit should occur in patients when they stop treatment, whether due to 
disease progression or unmanageable toxicity.   
 
The end of treatment visit will occur 21 to 30 days following completion of 
chemotherapy treatment: 
 Limited medical history and physical examination 
 Weight 
 ECOG Performance Status (see Appendices section 11.0) 
 LCSS; see section 6.9 and Appendices, section 11.3 
 FACT-L (Version 4); see section 6.9 and Appendices, section 11.4 
 Geriatric Assessment (Version 5); See section 6.7 and Appendices, section 
11.1 
 
Laboratory evaluations will be performed if last assessment was more than 
3 weeks prior to end-of-treatment visit:  CBC with differential; serum 
chemistries (sodium, potassium, chloride, bicarbonate, BUN, serum 
creatinine, glucose, calcium, phosphorus, magnesium, liver function tests 
(LFTs; total bilirubin, alkaline phosphatase, AST, ALT), total protein, 
albumin)  
 Blood sample for p16INK4a (confirm drawn on same day as CBC with 
differential) ; see section 6.6. 
 Concomitant medication(s) 
 Tumor evaluation (to include CT of chest, abdomen and pelvis) CNS 
imaging only required if felt clinically indicated by treating physician. 
 Toxicity assessment:  record any non-serious and serious AEs and assign 
appropriate toxicity grade (NCI CTCAE, Version 4).   
6.5 
Follow-up  
Follow-up will take place every 2 to 3 months after the end of treatment visit, for 
2 years or until death (whichever is first), and may be conducted via telephone. 
 
Follow-up will focus on survival status, follow-up of toxicity as necessary, any 
subsequent anti-cancer medication taken by the patient, and tumor evaluation at 
discretion of the physician. 


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6.6 
Whole blood for CBC and p16INK4a 
A whole blood sample will be taken for p16INK4a (confirm drawn on same day as 
CBC with differential).  The CBC with differential is necessary to normalize 
biomarker expression to the total lymphocyte count.  If CBC with differential 
already scheduled per standard of care on same day as blood draw for biomarker 
is scheduled, there is no need to repeat the CBC with differential.   
 
Processing of p16 blood samples: 
At the UNC site, after phlebotomy, the tube will be well-mixed and transported 
immediately to the Sharpless laboratory in the Lineberger Cancer Center for 
storage and processing.   
At external study sites, blood processing will be performed after phlebotomy, to 
yield a frozen T cell pellet.  The pellet will be stored at -80 degrees C until ready 
for shipment to the Sharpless laboratory for analysis.  Additional processing and 
shipping details will be provided in a study laboratory manual. 
 
Expression of p16INK4a is measured by quantitative Taqman RT-PCR.  
 
Blood samples for CBC and p16INK4a will be collected at baseline, on Day 1 of 
every odd numbered cycle beginning with cycle 3, and at the end of treatment 
visit. 
 
We are currently examining how expression of other senescence markers change 
with age in our study of normal adults. Should we find changes in any other 
senescence effectors we may perform exploratory analyses of these DNA markers 
(e.g. telomere length) and serum proteins in the future. Thus, excess serum and 
non-lymphoid cells remaining after assaying for p16INK4a  expression will be 
stored in the Sharpless laboratory (Room #21-225, Lineberger Comprehensive 
Cancer Center, CB #7295, University of North Carolina) for potential future use. 
6.7 
Geriatric Assessment (GA) (Version 5)  
After completing some initial demographic information, the first 3 formal items 
within the GA will be completed with the assistance of the study staff.   These 
include the Blessed Orientation-Memory-Concentration (BOMC) test, the 
Karnofsky Performance Status tool (KPS), and the Timed “Up and Go” test.  The 
BOMC consists of six questions designed to screen for macroscopic cognitive 
impairment[29]. The KPS is a general measure of patient independence in 
carrying out normal activities and self-care needs[29]. The Timed Up and Go is a 
performance test of physical mobility, and measures how long it takes the patient, 
in seconds, to stand up from a standard arm chair, walk a distance of 
approximately 10 feet, turn, walk back to the chair, and sit down again. Together, 
these 3 items should take approximately 10 minutes to complete on average.   
 
Following completion of the external evaluation, the patient will complete the 
patient questionnaire.  After answering 7 questions on their background 
(additional demographic information, see section I of patient questionnaire), 
patients will complete section II which includes a number of assessments 


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designed to evaluate their functional status.  The first tool is the Instrumental 
Activities of Daily Living (IADL, 7 questions), a subscale of the 
Multidimensional Functional Assessment Questionnaire (MFAQ): Older 
American Resources and Services (OARS).  Each question is scored from 0 
(completely unable) to 2 (without help) and sums to a score of 0-14.  This is 
followed by the Activities of Daily Living (ADL, 10 items) subscale of the 
Medical Outcomes Study (MOS) Physical Health.  Both the IADL questions and 
the ADL items are rated using a 3-point Likert scale measuring the degree to 
which an activity can be performed independently (see Section II).   Also included 
in section II is a self-reporting version of the KPS, developed to assess the 
patient’s perception of their own performance status.  This involves patient 
selection of 1 of 8 phrases that the patient believes best describes their functional 
status.   Section II ends by asking patients to report the number of times they’ve 
fallen in the last 6 months. 
 
Sections III & IV of the questionnaire include a co-morbidity scale (the Physical 
Health Section of the OARS) that contains a list of current illnesses and 
conditions an individual might have and the degree to which they impair daily 
activities, as well as a request for the patient to list all current medications they 
are taking.  A brief section on nutrition follows, comprised of 3 brief questions.  
Section VI involves an assessment of psychological distress and well-being and 
includes 17 questions from The Mental Health Index (MHI-17).   
 
The formal GA finishes with separate evaluations of social functioning (via the 4 
question MOS Social Activity Limitations Measure) and social support (via the 
12 item MOS Social Support Survey: Emotional/Information and Tangible 
subscales).  
 
Once the GA is completed, the evaluation ends with 4 questions evaluating 
patient satisfaction with the self-administered portion of the GA. 
 
The Geriatric Assessment will be administered prior to treatment and at the end of 
treatment visit.  (See Appendices, Section 11.1 below) 
6.8 
Health Behaviors Questionnaire 
Patients will be asked to complete a brief health behaviors questionnaire at study 
entry, regarding their smoking and exercise habits, and weekly alcohol 
consumption (see Appendices, section 11.2). 
6.9 
Assessment of Quality of Life 
Quality of life will be evaluated using the lung cancer symptom scale (LCSS) and 
the Functional Assessment of Cancer Therapy-Lung (FACT-L, Version 4) scale. 
 
LCSS and FACT-L will be administered prior to treatment, before each odd-
numbered treatment cycle (beginning with Cycle 3), and at the End of Treatment 
visit.  (See Appendices, sections 11.3 and 11.4) 
 


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For the LCSS, both a patient and observer rating scale will be completed.  
Additional documentation regarding the administration and scoring of the LCSS 
will be provided in the study manual. 
6.10 
Assessment of Safety  
The primary objective of this study will be tolerability of weekly nab-paclitaxel, 
as measured by occurrence of Grade 3 or worse toxicity after 6 cycles or 3 weeks 
after discontinuation of treatment, for those who come off treatment earlier. Grade 
3 and 4 toxicities of interest include those of clinical significance, such as 
neuropathy, myalgia, arthralgia, neutropenia, thrombocytopenia and anemia and 
those that are deemed clinically significant and considered related to nab-
paclitaxel by the treating physician. 
 
Any patient who receives treatment on this protocol will be evaluable for toxicity.  
The criteria used to assess toxicity are the National Cancer Institute (NCI), 
Common Terminology Criteria for Adverse Events (CTCAE), version 4.   
 
Further information on assessment for toxicity is provided in the time and events 
table (Section 6.0).  See section 4.4.1 for description of dose limiting toxicity and 
dose modifications. 
6.11 
Assessment of Efficacy 
Efficacy outcomes are secondary objectives for this study, and include OS, ORR, 
and PFS.  All patients who receive at least one dose of nab-paclitaxel will be 
evaluable for OS.  Patients who have received at least 2 cycles of therapy and 
have at least one post-baseline efficacy assessment after Cycle 2 will be evaluable 
for assessment of the secondary response objectives (ORR and PFS).  Patients 
who drop out of the study prior to the first formal tumor assessment for the reason 
of progression will be assessable and counted as having progressive disease.  
Patients who drop out of the study prior to the first formal tumor assessment for 
reasons other than progression will not be evaluable for ORR or PFS.  ORR and 
PFS will be assessed via RECIST1.1.  
6.11.1 Assessment of Disease-Tumor Measurement Based on RECIST 1.1 
See the international criteria proposed by the Response Evaluation Criteria in 
Solid Tumors (RECIST) Committee, version 1.1 (Eur J Cancer 45;2009:228-247) 
for additional details on RECIST1.1. 
 
Measurable disease will be defined as the presence of at least one measurable 
lesion that can be accurately measured in at least one dimension with the longest 
diameter a minimum size of: 
 >10mm by CT scan (CT scan slice thickness no greater than 5 mm) 
 10mm caliper measurement by clinical exam (lesions which cannot be 
accurately measured with calipers should be recorded as non-measurable). 
 20 mm by chest x-ray. 
 


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For malignant lymph nodes to be considered pathologically enlarged and 
measurable, a lymph node must be ≥15mm in short axis when assessed by CT 
scan (CT scan slice thickness recommended to be no greater than 5mm).  At 
baseline and in follow-up, only the short axis will be measured and followed.   
 
All other lesions, including small lesions (longest diameter <10mm or 
pathological lymph nodes with ≥10 to <15 mm short axis) as well as truly non-
measurable lesions, will be considered non-measurable.  Lesions considered truly 
non-measurable include: leptomeningeal disease; ascites; pleural/pericardial 
effusion; inflammatory breast disease; lymphangitic involvement of skin or lung, 
abdominal masses/abdominal organomegaly identified by physical exam that is 
not measurable by reproducible imaging techniques. 
 
All measurements should be recorded in metric notation, using calipers if 
clinically assessed. All baseline evaluations should be performed as close as 
possible to the treatment start 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 should always be done rather than clinical 
examination unless the lesion(s) being followed cannot be imaged but are 
assessable by clinical exam.  Clinical lesions will only be considered measurable 
when they are superficial and ≥10 mm diameter as assessed using calipers (e.g. 
skin nodules). For the case of skin lesions, documentation by color photography 
including a ruler to estimate the size of the lesions is recommended. 
6.11.2 Baseline Documentation of Target and Non-Target Lesions 
All measurable lesions up to a maximum of 5 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 longer 
diameter), be representative of all involved organs, but in addition should be those 
that lend themselves to reproducible repeated measurements.  
 
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, only the short axis is 
added into the sum.  The baseline sum diameters will be used as reference to 
further characterize the objective tumor response of the measurable dimension of 
the disease. 
 
All other lesions (or sites of disease) including pathological lymph nodes should 
be identified as non-target lesions and should also be recorded at baseline. 
Measurements are not required and these lesions should be followed as “present” 
or “absent,” or in rare cases “unequivocal progression.”   


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6.11.3 Evaluation of Target Lesions using RECIST 1.1 Criteria 
NOTE: In addition to the information below, also see section 4.3.2 in the 
international criteria proposed by the Response Evaluation Criteria in Solid 
Tumors (RECIST) Committee, version 1.1 (Eur J Cancer 45;2009:228-247) for 
special notes on the assessment of target lesions.  
 
Complete response (CR)−Disappearance of all target lesions.  Any pathological 
lymph node (LN) target or no must have decreased in short axis to <10mm. 
 
Partial response (PR)−At least a 30% decrease in the sum of the LD of the target 
lesions taking as reference the baseline sum LD. 
 
Progressive Disease (PD)−At least a 20% increase in the sum of the LD of the 
target lesions taking as reference the smallest sum LD recorded since the 
treatment started including baseline 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 5mm.  The appearance of one or more new lesions also constitutes PD. 
 
Stable disease (SD)−Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD taking as references the smallest sum LD since the 
treatment started. 
6.11.4 Evaluation of Non-Target Lesions using RECIST 1.1 Criteria 
Complete response (CR)−Disappearance of all non-target lesions and 
normalization of tumor marker levels.  All LN must be non-pathological in size 
(<10mm short axis).   
 
Non-complete response (non-CR)/non-progression (non-PD)−Persistence of one 
or more non-target lesion(s) or/and maintenance of tumor marker level above the 
normal limits. 
 
Progressive disease (PD)−Appearance of one or more new lesions and/or 
unequivocal progression of existing non-target lesions. 
6.11.5 Evaluation of Best Overall Response using RECIST 1.1 Criteria 
The best overall response is the best response recorded from the start of the study 
treatment until the end of treatment.  The best overall response will be defined 
according to the following table: 
 
 
 
 
 
 
 
 
 


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Overall 
Response First 
Time Point 
Overall Response 
Subsequent Time 
Point 
BEST Overall Response 
CR 
CR 
CR 
CR 
PR 
SD, PD, or PR1 
CR 
SD 
SD provided minimum criteria for SD duration met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD 
CR 
NE2 
SD provided minimum criteria for SD duration met, otherwise, 
NE2 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD 
PR 
NE2 
SD provided minimum criteria for SD duration met, otherwise, 
NE2 
NE 
NE2 
NE2 
1 If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR).  Best 
response would depend on whether minimum duration for SD was met.  However, sometimes ‘CR’ may be claimed 
when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the first 
time point.  Under these circumstances, the original CR should be changed to PR and the best response is PR.  
2  NE=not evaluable  
 
6.11.6 Sarcopenia: CTs of the chest, and, when available, abdomen, will be obtained at 
baseline and at the first disease assessment.  Exploratory analyses will be 
conducted evaluating the L3 muscle index if an adequate number of samples 
(abdominal CTs) are available or at L1 if an adequate number of samples are not.  
Baseline muscle indexes and their change at first disease assessment will be 
reported.  Both baseline measures and the change will be explored for association 
with toxicity, RR, PFS, OS and changes in quality of life. 
 
7.0 
ADVERSE EVENTS 
7.1 
Definitions  
7.1.1 Adverse Event (AE) 
An adverse event (AE) is any noxious, unintended, or untoward medical 
occurrence that may appear or worsen in a subject during the course of a study. It 
may be a new intercurrent illness, a worsening concomitant illness, an injury, or 
any concomitant impairment of the subject’s health, including laboratory test 
values (as specified by the criteria below), regardless of etiology. Any worsening 


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(i.e., any clinically significant adverse change in the frequency or intensity of a 
preexisting condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the electronic case report from (e-CRF) 
rather than the individual signs or symptoms of the diagnosis or syndrome. An 
overdose, accidental or intentional, whether or not it is associated with an AE, or 
abuse, withdrawal, sensitivity or toxicity to an investigational product should be 
reported as an AE. If an overdose is associated with an AE, the overdose and 
adverse event should be reported as separate terms. 
 
An abnormal laboratory value is considered to be an AE if the abnormality: 
 results in discontinuation from the study; 
 requires treatment, modification/interruption of the dose of the drug, or 
any therapeutic intervention; or  
 is judged to be of significant clinical importance. 
 
Regardless of severity grade, only laboratory abnormalities that fulfill a 
seriousness criterion need to be documented as a serious adverse event. 
 
If a laboratory abnormality is one component of a diagnosis or syndrome, then 
only the diagnosis or syndrome should be recorded on the AE page/screen of the 
electronic case report form (eCRF). If the abnormality was not a part of a 
diagnosis or syndrome, then the laboratory abnormality should be recorded as the 
AE. 
 
Hospitalization for elective surgery or routine clinical procedures that are not the 
result of an AE (e.g., surgical insertion of central line) need not be considered 
AEs and should not be recorded as an AE.  Disease progression should not be 
recorded as an AE, unless it is attributable by the investigator to the study therapy. 
 
In this study, toxicity will be assessed according to the NCI Common 
Terminology Criteria for Adverse Events (CTCAE), version 4.0, available at: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
7.1.2 Suspected Adverse Reaction (SAR) 
A suspected adverse reaction (SAR) is any AE for which there is a reasonable 
possibility that the drug is the cause.  Reasonable possibility means that there is 
evidence to suggest a causal relationship between the drug and the AE.  A 
suspected adverse reaction implies a lesser degree of certainty about causality 
than adverse reaction, which means any adverse event caused by a drug.   
 
Causality assessment to a study drug is a medical judgment made in consideration 
of the following factors: temporal relationship of the AE to study drug exposure, 
known mechanism of action or side effect profile of study treatment, other recent 
or concomitant drug exposures, normal clinical course of the disease under 
investigation, and any other underlying or concurrent medical conditions.  Other 
factors to consider in considering drug as the cause of the AE: 


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 
Single occurrence of an uncommon event known to be strongly 
associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-
Johnson Syndrome) 
 
One or more occurrences of an event not commonly associated 
with drug exposure, but otherwise uncommon in the population (e.g., 
tendon rupture); often more than once occurrence from one or multiple 
studies would be needed before the sponsor could determine that there is 
reasonable possibility that the drug caused the event.   
 
An aggregate analysis of specific events observed in a clinical trial 
that indicates the events occur more frequently in the drug treatment group 
than in a concurrent or historical control group 
7.1.3 Unexpected AE or SAR 
An AE or SAR is considered unexpected if the specificity or severity of it is not 
consistent with the applicable product information (e.g., Investigator’s Brochure 
(IB) for an unapproved investigational product or package insert/summary of 
product characteristics for an approved product).  Unexpected also refers to AEs 
or SARs that are mentioned in the IB as occurring with a class of drugs or as 
anticipated from the pharmacological properties of the drug, but are not 
specifically mentioned as occurring with the particular drug under investigation.   
7.1.4 Serious AE or SAR (or Pregnancy) 
An AE or SAR is considered serious if, in the view of either the investigator or 
sponsor, it results in any of the following outcomes: 
 Death; 
 Is life-threatening (places the subject at immediate risk of death 
from the event as it occurred); 
 Requires inpatient hospitalization (>24 hours) or prolongation of 
existing hospitalization;* 
 Results in congenital anomaly/birth defect; 
 Results in a persistent or significant incapacity or substantial 
disruption of the ability to conduct normal life functions; 
 Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered a serious 
adverse drug experience when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed 
in the definition.  For reporting purposes, also consider the occurrences 
of pregnancy as an event which must be reported as an important 
medical event. 
 
*Hospitalization for anticipated or protocol specified procedures such as 
administration of chemotherapy, central line insertion, metastasis interventional 
therapy, resection of primary tumor, or elective surgery, will not be considered 
serious adverse events. 
 
Pregnancy 


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For females of childbearing potential: Pregnancies and suspected pregnancies 
(including a positive pregnancy test regardless of age or disease state) of a female 
subject occurring while the subject is on nab-paclitaxel, or within 30 days of the 
last dose of nab-paclitaxel,  are considered immediately reportable events. See 
Reporting requirements below.   Nab-paclitaxel is to be discontinued 
immediately.    
 
The female subject should be referred to an obstetrician-gynecologist, preferably 
one experienced in reproductive toxicity for further evaluation and counseling. 
 
Male subjects: If a female partner of a male subject taking nab-paclitaxel 
becomes pregnant, the male subject taking nab-paclitaxel should notify the 
Investigator, and the pregnant female partner should be advised to call their 
healthcare provider immediately. 
7.2 
Documentation of non-serious AEs or SARs 
For non-serious AEs or SARs, documentation must begin from day 1 of study 
treatment and continue through the 30 day follow-up period after treatment is 
discontinued.   
 
Collected information should be recorded in the Case Report Forms (CRF) for 
that patient.  Please include a description of the event, its severity or toxicity 
grade, onset and resolved dates (if applicable), and the relationship to the study 
drug.    Documentation should occur at least monthly.  
7.3 
SAEs or Serious SARs (or Pregnancy-suspected or positive) 
7.3.1 Timing 
After informed consent but prior to initiation of study medications, only SAEs 
caused by a protocol-mandated intervention will be collected (e.g. SAEs related to 
invasive procedures such as biopsies, medication washout, etc).  
 
For any other experience or condition that meets the definition of an SAE or a 
serious SAR, recording of the event must begin from day 1 of study treatment and 
continue through the 30 day follow-up period after treatment is discontinued.  
7.3.2 Documentation and Notification 
These events (SAEs or Serious SARs) must be recorded in the SAE console 
within Oncore™ for that patient within 24 hours of learning of its occurrence.  To 
meet the requirements of Celgene (see section 7.3.4 below), all SAEs must also be 
recorded on a MedWatch3500A form and faxed to Celgene.   
7.3.3 Reporting  
IRB Reporting Requirements: 
UNC: 


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 
UNC will submit an aggregated list of all SAEs to the UNC IRB 
annually at the time of study renewal according to the UNC IRB policies 
and procedures. 
 
The UNC-IRB will be notified of all SAEs that qualify as an 
Unanticipated Problem as per the UNC IRB Policies using the IRB’s web-
based reporting system (see section 9.5.3) within 7 days of the Investigator 
becoming aware of the problem.   
 
Affiliate sites:   
 
For affiliate sites using a local IRB of record, please submit 
adverse events per local IRB policy. 
 
For affiliate sites relying on the UNC-IRB, an aggregated list of all 
SAEs will be submitted to the UNC IRB annually at the time of study 
renewal according to the UNC IRB policies and procedures. In addition, 
any SAEs that qualify as an Unanticipated Problem will be entered into 
Oncore and reported to the UNC IRB by the UNCCN Study Coordinator 
using the IRB’s web-based reporting system (see section 9.5.3) within 7 
days of the Investigator becoming aware of the problem.   
7.3.4 Expedited Reporting by Investigator to Celgene 
Serious adverse events (SAE) are defined above.  The investigator must inform 
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-004513) and 
the institutional protocol number (LCCC1210) 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. 
 
Within 24 hours of being made aware of any SAE or pregnancy (suspected or 
positive), the UNC Study Coordinator (for events at UNC), or the Affiliate Study 
Coordinator (for events at Affiliate sites) is responsible for informing Celgene by 
faxing the MedWatch form 3500A and any copies of relevant source 
documentation (e.g., hospital admission or discharge summary, laboratory or 
other test results) that pertain to the event to Celgene.  *For Affiliate sites, the 
3500A form should be faxed simultaneously to the UNCCN Study Coordinator. 
7.3.5 Celgene Drug Safety Contact Information: 
Celgene Corporation      
Global Drug Safety and Risk Management    


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Connell Corporate Park      
300 Connell Dr.   
Suite 6000     
Berkeley Heights, NJ  07922        
Fax: 
(908) 673-9115 
E-mail: drugsafety@celgene.com 
 
SAEs brought to the attention of the investigator at any time after cessation of 
study drug medication and considered by the investigator to be related or possibly 
related to study drug medication must be reported to Celgene if and when they 
occur. 
 
Pregnancy Follow-Up 
The Investigator will follow the female subject until completion of the pregnancy, 
and must notify the UNC Study Coordinator (for events at UNC), or the UNCCN 
Study Coordinator (for events at Affiliate sites) 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 within 24 hours of the 
Investigator’s knowledge of the event (follow reporting requirements above). 
 
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 the nab-paclitaxel 
should also be reported to Celgene within 24 hours of the Investigator’s 
knowledge of the event. 
7.4 
Data and Safety Monitoring Plan 
The Principal Investigator will provide continuous monitoring of patient safety in 
this trial with periodic reporting to the Data and Safety Monitoring Committee 
(DSMC).  
 
Meetings/teleconferences will be held at a frequency dependent on study accrual, 
and in consultation with the study Biostatistician.  These meetings will include the 
investigators as well as protocol nurses, clinical research associates, regulatory 
associates, data managers, biostatisticians, and any other relevant personnel the 
principal investigators may deem appropriate.  At these meetings, the research 
team will discuss all issues relevant to study progress, including enrollment, 
safety, regulatory, and data collection. 
 
The team will produce summaries or minutes of these meetings. These summaries 
will be available for inspection when requested by any of the regulatory bodies 
charged with the safety of human subjects and the integrity of data including, but 
not limited to, the oversight (Office of Human Research Ethics (OHRE) 


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Biomedical IRB, the Oncology Protocol Review Committee (PRC) or the North 
Carolina TraCS Institute Data and Safety Monitoring Board (DSMB).   
 
The UNC LCCC Data and Safety Monitoring Committee (DSMC) will review the 
study on a regular (quarterly to annually) basis, with the frequency of review 
based on risk and complexity as determined by the UNC Protocol Review 
Committee.  The UNC PI will be responsible for submitting the following 
information for review: 1) safety and accrual data including the number of 
patients treated; 2) significant developments reported in the literature that may 
affect the safety of participants or the ethics of the study; 3) preliminary response 
data; and 4) summaries of team meetings that have occurred since the last report.  
Findings of the DSMC review will be disseminated by memo to the UNC PI, 
PRC, and the UNC IRB and DSMB.   
 
 
 
8.0 
STATISTICAL CONSIDERATIONS 
8.1 
Study Design/Study Endpoints 
This is a multicenter, single arm, phase II trial of 42 patients evaluating the 
tolerability of treatment with weekly nab-paclitaxel in elderly patients with 
advanced NSCLC who have progressed on at least one prior regimen. 
 
The primary study endpoint is clinically significant Grade 3 or higher toxicity 
associated with 6 cycles or 3 weeks after discontinuation of treatment, for those 
who come off treatment earlier.  Secondary endpoints include overall survival, 
progression-free survival, response rate, quality of life and correlation of Geriatric 
Assessment measures and p16 levels with treatment outcomes, overall grade 3 or 
higher toxicity, and specific toxicities. 
8.2 
Sample Size and Accrual 
The null hypothesis that the rate of grade 3/4/5 toxicity after 6 cycles (or 3 weeks 
after discontinuation of treatment, for those who come off treatment earlier) is 
60% will be tested against the one-sided alternative that the grade 3/4/5 toxicity 
rate is lower.  (Alternatively written, the null hypothesis that the toxicity-free rate 
is 40% will be tested against the one-sided alternative that the toxicity-free rate is 
higher than 40%.) A Simon’s two-stage design with a relaxed futility stopping 
rule will be used. In the first stage, toxicity will be assessed after the second cycle, 
or 3 weeks after discontinuation of treatment, for those who come off treatment 
earlier.  In the second stage, toxicity will be determined after 6 cycles, or 3 weeks 
after discontinuation of treatment, for those who come off treatment earlier. 
 
In the first stage, 25 patients will be accrued.  If there are 10 or fewer patients that 
are grade 3/4/5 toxicity-free in these 25, the study will be stopped for futility. 
Otherwise, 17 additional patients will be accrued for a total of 42. The null 
hypothesis will be rejected if 23 or more patients are grade 3/4/5 toxicity-free 


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after 6 cycles, or 3 weeks after discontinuation of treatment, for those who come 
off treatment earlier. Assuming that the toxicity-free rate after 2 cycles has a 
uniform distribution, uniform (0, 0.3) under the null hypothesis, and can be at 
most 40% under the alternative, this design yields a type I error rate of at most 
0.0375 and power of at least 80% when the true toxicity-free rate is 60%.  
 
The total accrual for this study is 42 patients; the expected accrual rate is 3 
patients per month, and is expected to occur within 14 months. 
8.3 
Data Analysis Plans 
The percentage of patients with a grade 3 or higher toxicity after 6 cycles (or 3 
weeks after discontinuation of treatment, for those who come off treatment 
earlier) and overall response rate (as measured by standard RECIST1.1 criteria) 
will be reported with an exact 95% confidence interval (CI).  Progression-free 
survival and overall survival will be evaluated by the Kaplan-Meier method and 
median with 95% CIs will be reported. 
 
The association of baseline components of the GA and p16 with the occurrence of 
a grade 3 or higher toxicity will be evaluated using the Wilcoxon Rank Sum tests 
for continuous variables and Fisher’s Exact tests for categorical variables.  Cox 
regression and the Kaplan-Meier Method will be used to evaluate associations 
with time to event analyses.  Longitudinal analyses will be used to explore the 
changes in LCSS over the course of the study.   
 
9.0 
STUDY MANAGEMENT 
9.1 
Institutional Review Board (IRB) Approval and Consent 
It is expected that the IRB will have the proper representation and function in 
accordance with federally mandated regulations.  The IRB should approve the 
consent form and protocol. 
 
In obtaining and documenting informed consent, the investigator should comply 
with the applicable regulatory requirement(s), and should adhere to Good Clinical 
Practice (GCP) and to ethical principles that have their origin in the Declaration 
of Helsinki. 
 
 
 
Before recruitment and enrollment onto this study, the patient will be given a full 
explanation of the study and will be given the opportunity to review the consent 
form. Each consent form must include all the relevant elements currently required 
by the FDA Regulations and local or state regulations. Once this essential 
information has been provided to the patient and the investigator is assured that 
the patient understands the implications of participating in the study, the patient 
will be asked to give consent to participate in the study by signing an 
IRB-approved consent form. 
 


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Prior to a patient’s participation in the trial, the written informed consent form 
should be signed and personally dated by the patient and by the person who 
conducted the informed consent discussion. 
9.2 
Required Documentation 
Before the study can be initiated at any site, the following documentation must be 
provided to the Clinical Protocol Office (CPO) at the University of North 
Carolina. 
 
 A copy of the official IRB approval letter for the protocol and 
informed consent 
 IRB membership list 
 CVs and medical licensure for the principal investigator and any 
sub-investigators who will be involved in the study. 
 Form FDA 1572 appropriately filled out and signed with 
appropriate documentation (NOTE: this is required if UNC holds the 
IND.  Otherwise, the Investigator’s signature documenting 
understanding of the protocol and providing commitment that this trial 
will be conducted according to all stipulations of the protocol is 
sufficient to ensure compliance) 
 CAP and CLIA Laboratory certification numbers and institution 
lab normal values 
 Executed clinical research contract 
9.3 
Registration Procedures 
All patients must be registered with the CPO at the University of North Carolina 
before enrollment to study.  For UNC patients, prior to registration, eligibility 
criteria must be confirmed with the UNC Study Coordinator. To register a patient, 
call the Oncology Protocol Office at 919-966-4432 Monday through Friday, 
9:00AM-5:00PM.  
 
For Affiliate patients, please contact the UNCCN Study Coordinator to ensure 
there is an opening available on the study for the potential subject (direct line 919-
966-7359), Monday through Friday, 9:00AM-5:00PM. To register a patient, 
please fax registration forms and eligibility documents to 919-966-4300.  
9.4 
Data Management and Monitoring/Auditing 
The UNCCN of the UNC LCCC will serve as the coordinating center for this 
trial. Data will be collected through a web based clinical research platform, 
OnCore®.  Other study institutions will be given a password to directly enter their 
own data onto the web site via electronic case report forms (eCRFs).  UNCCN 
personnel will coordinate and manage data for quality control assurance and 
integrity. 
 
All data will be collected and entered into OnCore® by Clinical Research 
Associates (CRAs) from UNC LCCC and participating institutions.  The 
investigators at each site will allow monitors to review all source documents 


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supporting data entered into OnCore®.     The UNCCN Data Coordinator can be 
reached at 919-843-2742 or 1-877-668-0683. 
 
As an investigator initiated study, this trial will also be audited by the Lineberger 
Cancer Center audit committee every six to twelve months, depending on 
participation of Affiliate sites. 
9.5 
Adherence to the Protocol 
Except for an emergency situation in which proper care for the protection, safety, 
and well-being of the study patient requires alternative treatment, the study shall 
be conducted exactly as described in the approved protocol.   
9.5.1 Emergency Modifications 
UNC and Affiliate investigators may implement a deviation from, or a change of, 
the protocol to eliminate an immediate hazard(s) to trial subjects without prior 
UNC or their respective institution’s IRB/IEC approval/favorable opinion.   
 
 
For Institutions Relying on UNC’s IRB: 
For any such emergency modification implemented, a UNC IRB modification 
form must be completed by UNC Research Personnel within five (5) business 
days of making the change.   
 
For Institutions Relying on Their Own IRB: 
For Affiliate investigators relying on their own institution’s IRB, as soon as 
possible after the modification has been made, the implemented deviation or 
change and the reasons for it should be submitted to: 
 
 
To UNC Principal Investigator for agreement  
 
The Affiliate institution’s IRB for review and approval.  
(Once IRB’s response is received, this should be forwarded to the 
UNCCN Regulatory Associate). 
9.5.2 Single Patient/Subject Exceptions 
For Institutions Relying on UNC’s IRB:  
Any request to enroll a single subject who does not meet all the eligibility criteria 
of this study requires the approval of the UNC Principal Investigator and the UNC 
IRB.  
 
For Institutions Relying on Their Own IRB: 
Any request to enroll a single subject who does not meet all the eligibility criteria 
of this study requires the approval of the UNC Principal Investigator and the 
participating institution’s IRB, per its policy.  Please forward the IRB response to 
the UNCCN Regulatory Associate by facsimile or via email within 10 business days 
after the original submission.   


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9.5.3 Other Protocol Deviations/Violations 
According to UNC’s IRB, a protocol deviation is any unplanned variance from an 
IRB approved protocol that:  
 Is generally noted or recognized after it occurs 
 Has no substantive effect on the risks to research participants 
 Has no substantive effect on the scientific integrity of the research plan 
or the value of the data collected  
 Did not result from willful or knowing misconduct on the part of the 
investigator(s).  
 
An unplanned protocol variance is considered a violation if the variance meets 
any of the following criteria:  
 Has harmed or increased the risk of harm to one or more research 
participants. 
 Has damaged the scientific integrity of the data collected for the study. 
 Results from willful or knowing misconduct on the part of the 
investigator(s). 
 Demonstrates serious or continuing noncompliance with federal 
regulations, State laws, or University policies. 
 
If a deviation or violation occurs please follow the guidelines below: 
 
For Institutions Relying on UNC’s IRB: 
Protocol Deviations: UNC or Affiliate personnel will record the deviation in 
OnCore®, and report to any sponsor or data and safety monitoring committee in 
accordance with their policies.  Deviations should be summarized and reported to 
the IRB at the time of continuing review. 
 
Protocol Violations: Violations should be reported by UNC personnel within one 
(1) week of the investigator becoming aware of the event using the same IRB 
online mechanism used to report Unanticipated Problems.   
 
For Institutions Relying on Their Own IRB: 
In addition to adhering to the policies regarding protocol compliance set forth by 
your institution’s IRB, the following is also required: 
 
Protocol Deviations: In the event a deviation from protocol procedures is 
identified, record the deviation in OnCore®. 
 
Protocol Violations: Any protocol violation that occurs must be reported to your 
IRB per institutional policies and reported to the UNCCN Study Coordinator 
within 5 days. UNC-CH will determine if the violation affects the safety of the 
patient and integrity of the data.  Once your institution’s IRB response is received, 
please forward to the UNCCN Regulatory Associate. 
 
Unanticipated Problems: 
Affiliate Sites: 


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Any events that meet the criteria for “Unanticipated Problems (UPs)” as defined 
by UNC’s IRB must also be reported to the UNCCN Study Coordinator.   The 
UNCCN Study Coordinator will report the event to the UNC IRB using the IRB’s 
web-based reporting system.  Examples of such UPs include a lost or stolen 
laptop computer that contains sensitive study information. 
 
UNC 
Any events that meet the criteria for “Unanticipated Problems” as defined by 
UNC’s IRB must be reported by the Study Coordinator using the IRB’s web-
based reporting system.   
9.6 
Amendments to the Protocol 
Should amendments to the protocol be required, the amendments will be 
originated and documented by the Principal Investigator at UNC.  It should also 
be noted that when an amendment to the protocol substantially alters the study 
design or the potential risk to the patient, a revised consent form might be 
required.   
 
For Institutions Relying on UNC’s IRB: 
The written amendment, and if required the amended consent form, must be sent 
to UNC’s IRB for approval prior to implementation.   
 
For Institutions Relying on Their Own IRB: 
Investigators must submit the UNC IRB approved amendment to their 
institution’s IRB for approval.  For multi-center studies, any affiliate site must 
submit their informed consent revisions to the UNCCN Regulatory Associate 
prior to submission to their IRB.   
9.7 
Record Retention 
Study documentation includes all eCRFs, data correction forms or queries, source 
documents, Sponsor-Investigator correspondence, monitoring logs/letters, and 
regulatory documents (e.g., protocol and amendments, IRB correspondence and 
approval, signed patient consent forms). 
 
Source documents include all recordings of observations or notations of clinical 
activities and all reports and records necessary for the evaluation and 
reconstruction of the clinical research study. 
 
Government agency regulations and directives require that all study 
documentation pertaining to the conduct of a clinical trial must be retained by the 
study investigator.  In the case of a study with a drug seeking regulatory approval 
and marketing, these documents shall be retained for at least two years after the 
last approval of marketing application in an International Conference on 
Harmonization (ICH) region.  In all other cases, study documents should be kept 
on file until three years after the completion and final study report of this 
investigational study. 


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9.8 
Obligations of Investigators 
The Principal Investigator is responsible for the conduct of the clinical trial at the 
site in accordance with Title 21 of the Code of Federal Regulations and/or the 
Declaration of Helsinki.  The Principal Investigator is responsible for personally 
overseeing the treatment of all study patients.  The Principal Investigator must 
assure that all study site personnel, including sub-investigators and other study 
staff members, adhere to the study protocol and all FDA/GCP/NCI regulations 
and guidelines regarding clinical trials both during and after study completion. 
 
The Principal Investigator at each institution or site will be responsible for 
assuring that all the required data will be collected and entered into the eCRFs. 
Periodically, monitoring visits will be conducted and the Principal Investigator 
will provide access to his/her original records to permit verification of proper 
entry of data. At the completion of the study, all eCRFs will be reviewed by the 
Principal Investigator and will require his/her final signature to verify the 
accuracy of the data. 
 
 


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10.0 REFERENCES 
1. 
Jemal, A., et al., Global cancer statistics. CA Cancer J Clin. 61(2): p. 69-90. 
2. 
Govindan, R., et al., Changing epidemiology of small-cell lung cancer in the 
United States over the last 30 years: analysis of the surveillance, epidemiologic, 
and end results database. J Clin Oncol, 2006. 24(28): p. 4539-44. 
3. 
Yang, P., et al., Clinical features of 5,628 primary lung cancer patients: 
experience at Mayo Clinic from 1997 to 2003. Chest, 2005. 128(1): p. 452-62. 
4. 
Howlader, N., et al., SEER Cancer Statistics Review, 1975-2008. 2010, Bethesda, 
MD: National Cancer Institute http://seer.cancer.gov/csr/1975_2008/, based on 
November 2010 SEER data submission, posted to the SEER web site, 2011. 
5. 
Owonikoko, T.K., et al., Lung cancer in elderly patients: an analysis of the 
surveillance, epidemiology, and end results database. J Clin Oncol, 2007. 25(35): 
p. 5570-7. 
6. 
Quoix, E.A., et al., Weekly paclitaxel combined with monthly carboplatin versus 
single-agent therapy in patients age 70 to 89: IFCT-0501 randomized phase III 
study in advanced non-small cell lung cancer (NSCLC). Journal of Clinical 
Oncology, 2010. 28(15s): p. 2. 
7. 
Quoix, E., et al., Carboplatin and weekly paclitaxel doublet chemotherapy 
compared with monotherapy in elderly patients with advanced non-small-cell 
lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet., 2011. 378(9796): p. 
1079-88. Epub 2011 Aug 8. 
8. 
Scagliotti, G.V., et al., Phase III study comparing cisplatin plus gemcitabine with 
cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage 
non-small-cell lung cancer. J Clin Oncol, 2008. 26(21): p. 3543-51. 
9. 
Kim, E.S., et al., Gefitinib versus docetaxel in previously treated non-small-cell 
lung cancer (INTEREST): a randomised phase III trial. Lancet, 2008. 372(9652): 
p. 1809-18. 
10. 
Hanna, N., et al., Randomized phase III trial of pemetrexed versus docetaxel in 
patients with non-small-cell lung cancer previously treated with chemotherapy. J 
Clin Oncol, 2004. 22(9): p. 1589-97. 
11. 
Shepherd, F.A., et al., Erlotinib in previously treated non-small-cell lung cancer. 
N Engl J Med, 2005. 353(2): p. 123-32. 
12. 
Shepherd, F.A., et al., Prospective randomized trial of docetaxel versus best 
supportive care in patients with non-small-cell lung cancer previously treated 
with platinum-based chemotherapy. J Clin Oncol, 2000. 18(10): p. 2095-103. 
13. 
Fossella, F.V., et al., Randomized phase III trial of docetaxel versus vinorelbine 
or ifosfamide in patients with advanced non-small-cell lung cancer previously 
treated with platinum-containing chemotherapy regimens. The TAX 320 Non-
Small Cell Lung Cancer Study Group. J Clin Oncol, 2000. 18(12): p. 2354-62. 
14. 
Weiss, G.J., et al., Elderly patients benefit from second-line cytotoxic 
chemotherapy: a subset analysis of a randomized phase III trial of pemetrexed 
compared with docetaxel in patients with previously treated advanced non-small-
cell lung cancer. J Clin Oncol, 2006. 24(27): p. 4405-11. 
15. 
Wheatley-Price, P., et al., Erlotinib for advanced non-small-cell lung cancer in 
the elderly: an analysis of the National Cancer Institute of Canada Clinical Trials 
Group Study BR.21. J Clin Oncol, 2008. 26(14): p. 2350-7. 


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16. 
Ibrahim, N.K., et al., Phase I and pharmacokinetic study of ABI-007, a 
Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin 
Cancer Res, 2002. 8(5): p. 1038-44. 
17. 
M. A. Socinski, I.N.B., N. A. Karaseva, A. Makhson, I. Vynnychenko, I. 
Okamoto, J. K. Hon, V. Hirsh, P. Bhar, J. Iglesias, Results of a randomized, phase 
III trial of nab-paclitaxel (nab-P) and carboplatin (C) compared with cremophor-
based paclitaxel (P) and carboplatin as first-line therapy in advanced non-small 
cell lung cancer (NSCLC). J Clin Oncol 28:18s, 2010 (suppl; abstr LBA7511), 
2010. 
18. 
Socinski, M.A., 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 Cancer: Final Results of a Phase 
III Trial. J Clin Oncol, 2012. 30(17): p. 2055-62. 
19. 
Socinski, M.A., I. N. Bondarenko, N. A. Karaseva, A. Makhson, I. Vynnychenko, 
I. Okamoto, J. K. Hon, V. Hirsh, P. Bhar, G. I. Berk, J. L. Iglesias, 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 29: 2011 (suppl; abstr 7551)  
20. 
Belani, C.P., et al., Randomized, phase III study of weekly paclitaxel in 
combination with carboplatin versus standard every-3-weeks administration of 
carboplatin and paclitaxel for patients with previously untreated advanced non-
small-cell lung cancer. J Clin Oncol, 2008. 26(3): p. 468-73. 
21. 
Socinski, M.A., 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(6): p. 852-61. 
22. 
Hurria, A., et al., Implementing a geriatric assessment in cooperative group 
clinical cancer trials: CALGB 360401. J Clin Oncol. 29(10): p. 1290-6. 
23. 
Liu, Y., et al., Expression of p16(INK4a) in peripheral blood T-cells is a 
biomarker of human aging. Aging Cell, 2009. 8(4): p. 439-48. 
24. 
Muss, H.B., et al., P16INK4a expression after chemotherapy in older women with 
early-stage breast cancer. Journal of Clinical Oncology, 2011. 29 (suppl; abstr 
9002). 
25. 
Hollen, P.J., et al., Measurement of quality of life in patients with lung cancer in 
multicenter trials of new therapies. Psychometric assessment of the Lung Cancer 
Symptom Scale. Cancer., 1994. 73(8): p. 2087-98. 
26. 
Cella, D.F., et al., Reliability and validity of the Functional Assessment of Cancer 
Therapy-Lung (FACT-L) quality of life instrument. Lung Cancer, 1995. 12(3): p. 
199-220. 
27. 
ten Tije, A.J., et al., Pharmacological effects of formulation vehicles : 
implications for cancer chemotherapy. Clin Pharmacokinet, 2003. 42(7): p. 665-
85. 
28. 
Robidoux, A., 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(1): p. 81-6. 
29. 
Hurria, A., et al., Developing a cancer-specific geriatric assessment: a feasibility 
study. Cancer, 2005. 104(9): p. 1998-2005. 
 


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11.0 APPENDIX A:  ECOG Performance Status 
 
Grade 
Activity Level 
0 
Fully active; no performance restrictions 
1 
Strenuous physical activity restricted; 
fully ambulatory and able to carry out 
light work 
2 
Capable of all self-care but unable to carry 
out any work activities. Up and about >50 
percent of waking hours 
3 
Capable 
of 
only 
limited 
self-care; 
confined to bed or chair >50 percent of 
waking hours 
4 
Completely disabled; cannot carry out any 
self-care; totally confined to bed or chair 
5 
Dead 
 
 
Reference:   
Oken MM, Creech RH, Tormey DC, et al.  Toxicity and response criteria of the eastern 
cooperative oncology group.  Am J Clin Oncol 1982; 5: 649-55. 
 
 


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11.1 
APPENDIX C:  Geriatric Assessment (Version 5) 
11.1.1 Geriatric Assessment:  Data to be Gathered by the Healthcare Team 
 


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11.1.2 Geriatric Assessment: Patient Questionnaire 
 


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11.2 
APPENDIX D:  Health Behaviors Questionnaire (Version 1) 
 
 


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11.3 
APPENDIX E:   Lung Cancer Symptom Scale  
11.3.1 Lung Cancer Symptom Scale:  Observer Form 
 
Name of Subject: ____________________________________________________ 
 
Date of Protocol:  ____________________________________________________ 
 
Name of Observer:  __________________________________________________ 
 
Date of Assessment:  _________________________________________________ 
 
LUNG CANCER SYMPTOM SCALE (LCSS):   OBSERVER FORM 
 
 
Directions:  Direct the interview to assess lung cancer symptoms using the 
timeframe of  
                     DURING  THE  PAST  DAY (within the last 24 hours).  
 
 
 
1.  Loss of appetite:  (Score:   _____) 
 
       100   None.  
         75   Mild; occasional loss of appetite but does not interfere with food intake.   
         50   Moderate; occasional loss of appetite which occasionally interferes with 
food intake. 
         25   Marked; frequent loss of appetite which generally interferes with food 
intake. 
           0   Severe; appetite so poor that medical intervention for feeding 
(intravenously or feeding tube) is needed. 
 
 
2.  Fatigue:  (Score: _____) 
 
       100   None. 
         75   Mild; occasionally troubled by modest fatigue. 
         50   Moderate; usually troubled by modest fatigue. 
         25   Marked; occasionally troubled by major fatigue. 
           0   Severe; usually troubled by major fatigue. 
 
 
3.  Cough:  (Score: _____) 
 
       100   None. 
         75   Mild; present and increased over a year ago, but not bothersome; no 
medications needed. 
         50   Moderate; bothersome; leads to SOB on occasion.  
         25   Marked; bothersome; disturbs sleep and other normal functioning. 
           0   Severe; nearly constant; disrupts any normal activities. 
 
 


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4.  Dyspnea:  (Score: _____)  
          
       100   None. 
         75   Mild; noticed only with major activity (e.g., climbing more than one 
flight of stairs);  
                SOB does not limit usual activities. 
         50   Moderate; present when walking at normal pace; interferes with ability 
to carry out  
                some usual activities. 
         25   Marked; present with minimal activity; supplemental O2 used only 
occasionally.  
           0   Severe; supplemental O2 required most or all of the time. 
 
 
5.  Hemoptysis:  (Score: _____) 
 
       100   None. 
         75   Mild; blood in sputum, less frequently than daily.  
        50   Moderate; blood in sputum at least daily but generally just "flecks" as 
part of the sputum. 
         25   Marked; sputum is often purely bloody (not just flecks) on a daily 
basis. 
           0   Severe; same as marked but blood loss by hemoptysis measurably 
lowering hemoglobin. 
 
 
6.  Pain:  (Score: ______) 
 
       100   None. 
       75   Mild; present but either no medications required or only non-narcotic, 
non-codeine type oral agents; pain control satisfactory or reasonable. 
         50   Moderate; codeine or codeine-containing oral medications needed; pain 
control satisfactory or reasonable. 
         25   Marked; narcotic oral agents are required; pain control satisfactory or 
reasonable. 
           0   Severe; narcotic oral medications required but pain control not 
satisfactory, or parenteral narcotics are required. 
 
 
The Lung Cancer Symptom Scale is reproduced with permission of Quality 
of Life Research Associates. 
 
 


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11.3.2 Lung Cancer Symptom Scale:  Patient Scale  
Note:  The LCSS Patient Scale will be administered in a cardset format versus 
single sheet of paper. 
 
Lung Cancer Symptom Scale (LCSS):  Patient scale 
 
English Version 
 
Directions: Please place a mark along each line where it would best describe the 
symptoms of your lung cancer DURING THE PAST DAY (within the last 24 
hours). 
 
Example Question: 
 
How good is the weather? 
 
        
As 
good 
as  it 
could 
be 
|_________________________________________________| 
As bad as  
it could be 
 
 
 
1.  How good is your appetite? 
 
As 
good 
as  it 
could 
be  
|_________________________________________________| 
As bad as  
it could be  
 
 
 
2.  How much fatigue do you have? 
 
                
None 
|_________________________________________________| 
As much as  
it could be 
 
 
 
3.  How much coughing do you have? 
 
                
None 
|_________________________________________________| 
As much as  
it could be  
 
 
 
4.  How much shortness of breath do you have? 
 
                
None 
|_________________________________________________| 
As much as  
it could be  


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5.  How much blood do you see in your sputum? 
 
                
None 
|_________________________________________________| 
As much as  
it could be  
 
 
 
6.  How much pain do you have? 
 
                
None 
|_________________________________________________| 
As much as  
it could be  
 
 
 
7.  How bad are your symptoms from lung cancer? 
 
 
 I have 
none 
|________________________________________________| 
As bad as  
they could be  
 
 
 
8.  How much has your illness affected your ability to carry out normal activities? 
 
    
Not at 
all 
|_________________________________________________| 
 
So much that  
I can do nothing for myself
 
 
 
9.  How would you rate the quality of your life today? 
 
          
Very 
high 
|_________________________________________________| 
 
Very low 
 
 
 


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11.4 
APPENDIX F:  Fact-L (Version 4) 
Below is a list of statements that other people with your illness have said are 
important. Please circle or mark one number per line to indicate your 
response as it applies to the past 7 days. 
 
 
PHYSICAL WELL-BEING 
 
Not 
at 
all 
A 
little 
bit 
Som
e-
what 
Quit
ea 
bit 
Very 
muc
h 
 
GP
1 
I have a lack of 
energy
 ......................................................................................... 
0 
1 
2 
3 
4 
GP
2 
I have 
nausea
 ......................................................................................... 
0 
1 
2 
3 
4 
GP
3 
Because of my physical condition, I have trouble meeting 
the needs of my 
family
 ......................................................................................... 
 
0 
 
1 
 
2 
 
3 
 
4 
GP
4 
I have 
pain
 ......................................................................................... 
0 
1 
2 
3 
4 
GP
5 
I am bothered by side effects of 
treatment
 ......................................................................................... 
0 
1 
2 
3 
4 
GP
6 
I feel 
ill
 ......................................................................................... 
0 
1 
2 
3 
4 
GP
7 
I am forced to spend time in 
bed
0 
1 
2 
3 
4 
 
 
SOCIAL/FAMILY WELL-BEING 
 
Not 
at 
all 
A 
little 
bit 
Som
e-
what 
Quit
ea 
bit 
Very 
muc
h 
 
GS
1 
I feel close to my 
friends
 ......................................................................................... 
0 
1 
2 
3 
4 
GS
2 
I get emotional support from my 
family
 ......................................................................................... 
0 
1 
2 
3 
4 


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Please circle or mark one number per line to indicate your response as it 
applies to the past 7 days. 
 
 
 
EMOTIONAL WELL-BEING 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
 
GE1 
I feel 
sad
  
0 
1 
2 
3 
4 
GE2 
I am satisfied with how I am coping with my 
illness
  
0 
1 
2 
3 
4 
GE3 
I am losing hope in the fight against my 
illness
  
0 
1 
2 
3 
4 
GS
3 
I get support from my 
friends
 ......................................................................................... 
0 
1 
2 
3 
4 
GS
4 
My family has accepted my 
illness
 ......................................................................................... 
0 
1 
2 
3 
4 
GS
5 
I am satisfied with family communication about my 
illness
 ......................................................................................... 
 
0 
 
1 
 
2 
 
3 
 
4 
GS
6 
I feel close to my partner (or the person who is my main 
support)
 ......................................................................................... 
 
0 
 
1 
 
2 
 
3 
 
4 
Q1 
Regardless of your current level of sexual activity, please 
answer the following question. If you prefer not to answer it, 
please mark this box           and go to the next section. 
 
 
 
 
 
GS
7 
I am satisfied with my sex 
life
0 
1 
2 
3 
4 


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GE4 
I feel 
nervous
  
0 
1 
2 
3 
4 
GE5 
I worry about 
dying
  
0 
1 
2 
3 
4 
GE6 
I worry that my condition will get 
0 
1 
2 
3 
4 
 
 
 
 
FUNCTIONAL WELL-BEING 
 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
 
GF1 
I am able to work (include work at 
home)
  
0 
1 
2 
3 
4 
GF2 
My work (include work at home) is 
fulfilling
  
0 
1 
2 
3 
4 
GF3 
I am able to enjoy 
life
  
0 
1 
2 
3 
4 
GF4 
I have accepted my 
illness
  
0 
1 
2 
3 
4 
GF5 
I am sleeping 
well
  
0 
1 
2 
3 
4 
GF6 
I am enjoying the things I usually do for 
fun
  
0 
1 
2 
3 
4 
GF7 
I am content with the quality of my life right 
0 
1 
2 
3 
4 
 
 
 


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Please circle or mark one number per line to indicate your response as it 
applies to the past 7 days. 
 
 
 
ADDITIONAL CONCERNS 
 
Not at 
all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
 
B1 
I have been short of 
breath
 ........................................................................................  
0 
1 
2 
3 
4 
C2 
I am losing 
weight
 ........................................................................................  
0 
1 
2 
3 
4 
L1 
My thinking is 
clear
 ........................................................................................  
0 
1 
2 
3 
4 
L2 
I have been 
coughing
 ........................................................................................  
0 
1 
2 
3 
4 
B5 
I am bothered by hair 
loss
 ........................................................................................  
0 
1 
2 
3 
4 
C6 
I have a good 
appetite
 ........................................................................................  
0 
1 
2 
3 
4 
L3 
I feel tightness in my 
chest
 ........................................................................................  
0 
1 
2 
3 
4 
L4 
Breathing is easy for 
me
 ........................................................................................  
0 
1 
2 
3 
4 
Q3 
Have you ever smoked?  
No ___  Yes ___  If yes: 
L5 
I regret my 
smoking
0 
1 
2 
3 
4