A Randomized, Placebo-Controlled, Double-Blind, Phase II Trial of Nanoparticle Albumin-Bound Paclitaxel (Nab-Paclitaxel, Abraxane®) With or Without Mifepristone for Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer
Phase: PHASE2
Conditions: Breast Cancer
Sponsor: University of Chicago

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Local Protocol #: IRB16-0403; NCT#: NCT02788981 
       
 
TITLE: “A Randomized, Placebo-Controlled, Double-Blind, Phase II Trial of Nanoparticle 
Albumin-bound Paclitaxel (nab-paclitaxel, Abraxane®) with or without Mifepristone for 
Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer”. 
 
 
Coordinating Center: 
The University of Chicago 
 
 
Principal Investigator: 
Rita Nanda, M.D.* 
The University of Chicago 
5841 S. Maryland Ave., MC 2115 
Chicago, IL 60637-1470 
P: 773-834-2756 
F: 773-702-0963 
rnanda@medicine.bsd.uchicago.edu 
 
Gini Fleming, M.D. 
The University of Chicago 
5841 S. Maryland Ave., MC 2115 
Chicago, IL 60637-1470 
P: 773-702-6712 
F: 773-702-0188 
gfleming@medicine.bsd.uchicago.edu 
 
 
Co-Investigator/s: 
Suzanne Conzen, M.D. 
The University of Chicago 
5841 S. Maryland Ave., MC 2115 
Chicago, IL 60637-1470 
P: 773-834-2604 
F: 773-702-0188 
sconzen@medicine.bsd.uchicago.edu 
 
Statistician: 
Theodore (Ted) Karrison, Ph.D. 
The University of Chicago 
5841 S. Maryland Ave., MC 2000 
Chicago, IL 60637-1470 
P: 773-702-9326 
F: 773-702-1979 
 
 
This study is being conducted by institutional members of the Personalized Cancer Care 
Consortium (PCCC) as well as additional non-PCCC sites. 

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IND Sponsor: *Rita Nanda, MD (IND #113205) 
 
Protocol Type / Version # / Version Date: 
Original / Version # 1 / 5-15-2016 
Amendment 1/ Version #2 / 3-29-2017 
Amendment 2/ Version #3/ 7-16-2018 

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This is a randomized, placebo-controlled, double-blind, phase II trial of nab-paclitaxel with or 
without mifepristone for advanced, triple-negative breast cancer. A total of 72 patients will 
receive nab-paclitaxel 100 mg/m2 on days 1, 8 and 15 of each 28 day cycle: patients will be 
randomly assigned to either receive placebo (n=36 patients) or to receive mifepristone 300 mg 
daily on the day prior to and day of each dose of nab-paclitaxel (n=36 patients). Patients will 
be enrolled over 24 months and followed for 12 months following completion of study. The 
primary endpoint will be to compare the progression- free survival (PFS) of patients treated 
with nab-paclitaxel plus mifepristone versus patients treated with nab-paclitaxel plus placebo. 
 
To expand and follow up on our understanding of a potential PK interaction between nab- 
paclitaxel and mifepristone, we will perform PK studies in the first 20 patients enrolled at pre- 
specified “PK sites”. Patients in this portion of the study will have paclitaxel levels drawn at 
pre-specified time points (at baseline, and then 15 mins, 45 mins, 4 hrs, 6 hrs, and 24 hrs after 
the end of nab-paclitaxel infusion). These patients will not receive mifepristone or placebo 
week one; mifepristone or placebo will start week two. Paclitaxel levels will be drawn 
cycle1/day1-2 and cycle1/day8-9. PK results will not be required to proceed with the study and 
will not be performed in real time. 
 
Day (of 28 day cycle) 
Treatment 
0 
1 
7 
8 
14 
15 
nab-paclitaxel 
X 
X 
X 
Mifepristone* 
X 
X 
X 
X 
X 
X 
 
*Patients enrolled on PK portion of study will not receive mifepristone or placebo week one; 
mifepristone or placebo will start week two. 
 
 
 
 
 
 
 
 
Arm A: 
Nab-paclitaxel + Placebo 
Arm B: 
Nab-paclitaxel + Mifepristone 
1:1 
Randomization 
Disease 
Progression 

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SCHEMA 
 
 
 
Key Patient Eligibility 
(for full list refer to Section 3) 
Required Laboratory Data 
Metastatic or locally advanced breast cancer not 
amenable to local therapy. 
Triple negative breast cancer (defined as ER and 
PR <10% positive; HER2 0-1+ by IHC or FISH 
ratio < 2.0) 
Measurable disease. 
ECOG PS 0-2. 
Age > 18 years. 
Non-pregnant and not breast feeding. 
Up to two prior cytotoxic therapies for metastatic 
disease. 
No prior therapy with nab-paclitaxel for 
metastatic disease. 
Patients with brain metastases will be eligible 
provided brain metastases have been treated and 
steroids have been discontinued for at least 7 
days. 
No currently active secondary malignancy. 
Peripheral neuropathy < grade 2. 
No other serious medical or psychiatric disease. 
No serious active infection (viral, fungal, 
bacterial). 
No infection requiring parenteral antibiotics at the 
time of registration. 
No long term or concurrent use of corticosteroid 
therapy 
Absolute neutrophils > 1,500/uL 
Platelets 
> 100,000/uL 
Hemoglobin 
> 9.0 g/dL 
Bilirubin 
< 1.5 mg/dL 
AST and ALT 
<  2.5 ULN* 
(if liver mets present <  5 X ULN) 
Alkaline phosphatase < 2.5 X ULN 
(if bone mets present < 5 X ULN) 
Creatinine (Cr) 
< ULN 
Cr clearance 
> 60 mL/min/1.73m2 
(if Cr above ULN) 
INR 
< 1.5 
 
* ULN = upper limit of normal 

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TABLE OF CONTENTS 
1. 
OBJECTIVES ...................................................................................................................... 7 
1.1 
Primary Objective .................................................................................................... 7 
1.2 
Secondary Objectives .............................................................................................. 7 
1.3 
Exploratory Objectives ............................................................................................ 7 
2. 
BACKGROUND ................................................................................................................. 7 
2.1 
Breast Cancer ........................................................................................................... 7 
2.2 
Nab-paclitaxel (Abraxane) and breast cancer .......................................................... 7 
2.3 
Mifepristone............................................................................................................. 8 
2.4 
Rationale .................................................................................................................. 9 
2.5 
Correlative Studies Background ............................................................................ 10 
3. 
PATIENT SELECTION .................................................................................................... 10 
3.1 
Eligibility Criteria .................................................................................................. 10 
3.2 
Exclusion Criteria .................................................................................................. 12 
4. 
REGISTRATION PROCEDURES ................................................................................... 13 
4.1 
General Guidelines ................................................................................................ 13 
4.2 
Registration Process .............................................................................................. 13 
4.3 
Blinding Procedure ................................................................................................ 14 
4.4 
Unblinding Procedure ............................................................................................ 14 
5. 
TREATMENT PLAN. ....................................................................................................... 15 
5.1 
Agent Administration ............................................................................................ 15 
5.2 
General Concomitant Medication and Supportive Care Guidelines ...................... 16 
5.3 
Duration of Therapy .............................................................................................. 16 
5.4 
Duration of Follow Up .......................................................................................... 16 
5.5 
Criteria for Removal from Study ........................................................................... 17 
6. 
DOSING DELAYS/DOSE MODIFICATIONS ............................................................... 17 
7. 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ............................ 19 
7.1 
Adverse Event Characteristics ............................................................................... 19 
7.2 
Adverse Event Definitions. .................................................................................... 19 
7.3 
Adverse Event Reporting Requirements ............................................................... 22 
8. 
PHARMACEUTICAL INFORMATION ........................................................................ 23 
8.1 
Investigational Agent Description and Management ............................................ 23 
8.2 
Commercial Agent(s) ............................................................................................ 24 
9. 
BIOMARKER, CORRELATIVE, AND SPECIAL STUDIES ........................................ 25 
10. 
STUDY CALENDAR ....................................................................................................... 27 
11. 
MEASUREMENT OF EFFECT ....................................................................................... 28 
11.1 
Antitumor Effect – Solid Tumors .......................................................................... 28 

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12. 
DATA REPORTING ......................................................................................................... 34 
13. 
STATISTICAL CONSIDERATIONS .............................................................................. 34 
13.1 
Study Design/Endpoints ........................................................................................ 34 
13.2 
Sample Size/Accrual Rate ..................................................................................... 34 
13.3 
Stratification Factors. ............................................................................................. 35 
13.4 
Analysis of Secondary Endpoints .......................................................................... 35 
13.5 
Reporting and Exclusions ...................................................................................... 35 
14. 
STUDY MANAGEMENT AND REGULATORY AFFAIRS ......................................... 36 
14.1 
Multicenter Guidelines .......................................................................................... 36 
14.2 
Institutional Review Board (IRB) Approval and Consent ..................................... 36 
14.3 
Food and Drug Administration (FDA) Approval .................................................. 36 
14.4 
Required Documentation ....................................................................................... 36 
14.5 
Data and Safety Monitoring .................................................................................. 37 
14.6 
Auditing ................................................................................................................. 38 
14.7 
Amendments to the Protocol ................................................................................. 39 
14.8 
Annual IRB Renewals, Continuing Review and Final Reports. ............................ 39 
14.9 
Record Retention ................................................................................................... 39 
14.10 Obligations of Study Site Investigators ................................................................. 39 
REFERENCES .............................................................................................................................. 41 
APPENDIX A:  PERFORMANCE STATUS CRITERIA ........................................................... 43 
APPENDIX B: MULTICENTER GUIDELINES ........................................................................ 43 
APPENDIX C: CONCURRENT MEDICATION RESTRICTIONS ........................................... 44 

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1. OBJECTIVES 
 
1.1 
Primary Objective 
 
Progression-free survival (PFS): To compare the progression free survival (PFS) of patients 
with GR-positive, triple-negative breast cancer treated with nab-paclitaxel + placebo and 
patients treated with nab-paclitaxel + mifepristone 
 
1.2 
Secondary Objectives 
 
1.2.1 To correlate percentage glucocorticoid receptor (GR) positivity in the most recent 
metastatic tumor biopsy (or in primary tumor if only primary tumor is available) with 
PFS in mifepristone and placebo groups of patients with GR-positive, triple-negative 
breast cancer 
 
1.2.2 To perform an exploratory assessment of overall response rate in both groups of 
patients with GR-positive, triple-negative breast cancer 
 
1.2.3 To collect information regarding overall survival in both treatment cohorts of patients 
with GR-positive, triple-negative breast cancer 
 
1.3 
Exploratory Objectives 
To expand on our understanding of the interaction between nab-paclitaxel and 
mifepristone by performing PK studies in the first 20 patients enrolled at pre-specified 
PK sites. 
 
2. BACKGROUND 
 
2.1 
Breast Cancer 
 
Breast cancer is the second highest cause of cancer death in women in the United States[1]. 
While breast cancer is being diagnosed at earlier stages because of mammography, 
approximately 20-30% of patients go on to develop distant metastases, and about 6-10% of 
women in the U.S. present with metastatic disease. Chemotherapy and hormone therapy have 
both been used in the treatment of metastatic disease. Most patients initially experience an 
objective response, with responses lasting anywhere from 8-14 months. Unfortunately, 
progression of disease is inevitable, and response to second-line therapy is less likely less 
durable [2]. 
 
2.2 
Nab-paclitaxel (Abraxane) and breast cancer 
 
Paclitaxel is a taxane derivative that is among the most active agents in the treatment of breast 
cancer. Paclitaxel inhibits mitosis and leads to cell death by binding to dimeric tubulin and 
causing disruption of microtubule disassembly. Response rates in taxane naïve patients with 
metastatic breast cancer have ranged from 20-60%. Several studies have been conducted 
investigating the optimal dose and schedule of paclitaxel delivery. Weekly therapy appears to 
be more efficacious and has less hematologic toxicity than every three week dosing [3]. 

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One major limitation of paclitaxel is its poor water solubility. Due to poor solubility, paclitaxel 
must be dissolved in the solvent Cremophor EL and in relatively large volumes of fluid and 
administered over a 1-3 hour time period. Cremophor EL is associated with many side effects, 
including anaphylaxis, and thus requires premedication with both corticosteroids and 
antihistamines[4]. 
 
Nab-paclitaxel is an albumin-bound, solvent-free novel formulation of the insoluble drug 
paclitaxel that eliminates the need for pre-medications, including steroid premedication, and 
the risk of hypersensitivity from the paclitaxel solvent. The nanoparticles are stable in liquid 
suspensions and suitable for injection. This composition increases intra-tumoral concentrations 
of the drug by a receptor-mediated transport process allowing transcytosis across the 
endothelial cell wall, thus breaching the blood/tumor interface[5].  The maximum tolerated 
dose (MTD) in heavily pretreated patients was 100 mg/m2, given weekly for 3 weeks out of 
every 4 week cycle. A large phase II study evaluating weekly nab-paclitaxel demonstrated 
response rates of 14-16% in taxane-resistant, pre-treated metastatic breast cancer patients. 
Nab-paclitaxel was well tolerated when administered weekly over 30 minutes without steroids 
or growth factor support [6]. 
 
2.3 
Mifepristone 
 
Glucocorticoid receptor and breast cancer 
 
The glucocorticoid receptor (GR) is expressed in a significant subset of both ER alpha-positive 
and -negative human breast cancers.[7]. In vitro and in vivo experiments suggest that 
activation of the GR in ER-negative pre-malignant breast epithelial and cancer cells initiates 
cell survival pathways under otherwise apoptosis-inducing conditions (e.g. chemotherapy, 
radiation, and growth factor deprivation). Thus, GR antagonism is predicted to enhance 
chemotherapy sensitivity of GR+/ER- breast cancer cells by blocking stress-mediated cell 
survival pathways that would otherwise counteract chemotherapy-induced apoptosis in tumor 
cells [8]. 
 
In support of the hypothesis that GR activation via endogenous stress hormones mediates 
chemo-resistance (and associated increase risk of relapse for early stage ER- breast cancers), 
we recently examined the association between the levels of GR (NR3C1) gene expression and 
the pattern of GR target gene expression in human ER- breast cancers and cell lines. We found 
that in ER- early stage breast cancers, high GR expression in the primary tumor is associated 
with a significantly increased probability of relapse[9] This was not observed in ER+ early 
stage tumors. This analysis and previous data in breast and ovarian cancer have led to the 
hypothesis that “GR high” breast tumors demonstrate increased chemo-resistance through GR- 
mediated anti-apoptotic signaling and would be predicted to show an improved response to 
cytotoxic therapies if GR antagonist therapy is administered prior to chemotherapy [10]. 
Further data from the Conzen laboratory showed co-treatment with the GR-antagonist 
mifepristone both reverses GR-mediated gene expression in 3 TNBC cell lines and augments 
chemotherapy induced apoptosis [11]. 
 
Mifepristone 
 
Mifepristone is a progesterone and glucocorticoid receptor antagonist currently FDA approved 

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for termination of early pregnancy and the treatment of Cushing’s syndrome. It is also known 
to be a potent inhibitor of the GR[12]. Animal studies suggest that GR antagonism may be of 
value in the treatment of a variety of diseases such as glucocorticoid-dependent hypertension, 
arthritis, glaucoma, psychosis, addiction, and breast cancer [8, 12]. 
 
Cognition is adversely affected by high and sustained levels of glucocorticoids. In one small 
study, nine patients with mild to moderate Alzheimer’s disease, patients were treated with 
either mifepristone 200 mg per day or placebo for six weeks. The mifepristone-treated patients 
performed better on the cognitive subtest of the Alzheimer’s disease assessment scale, although 
the difference between patients treated with mifepristone and patients treated with placebo did 
not reach statistical significance [14, 15]. 
 
Many patients with psychotic depression have non-suppression of cortisol following 
dexamethasone administration. In addition, they can have increased urinary cortisol and 
increased serum ACTH levels. In one study of 30 patients with clinical depression, patients 
were randomly assigned to receive 50 mg, 600 mg or 1200 mg of mifepristone daily for seven 
days. Patients who received the higher two doses showed an improvement in symptomatology 
[16]. 
 
Since high cortisol levels have also been found in bipolar disorder, treatment with mifepristone 
has been explored as a potential therapy. In a study of 20 bipolar patients treated with either 
600 mg/day or placebo, those patients who received mifepristone had selective improvements 
in neurocognitive function, including memory performance, verbal fluency, spatial recognition 
and mood[18]. Mifepristone, however, has not been shown to be of any benefit for the 
management of schizophrenia [19] 
 
Several small single agent studies of mifepristone and another progesterone antagonist, 
onapristone, have been evaluated for the treatment of advanced breast cancer, with 
disappointing results [20-23]. However, these studies have been focused on the use of 
mifepristone as a PR antagonist. 
 
Mifepristone is a specific progesterone receptor and glucocorticoid receptor antagonist, with 
rare unexpected adverse effects, even at doses as high as 1200 mg. Common side effects of 
long term treatment with doses of up to 200 mg include fatigue, nausea, rash, cessation of 
menses in premenopausal women and hot flashes [24-26]. Hypothyroidism has rarely been 
observed with long term use, and is likely related to the antiglucocorticoid effect that inhibits 
iodine uptake induced by hydrocortisone and TSH [27, 28]. Low serum potassium has also 
been reported in breast cancer patients on long-term daily doses of 200 mg day and Cushing’s 
syndrome patients receiving up to 2000 mg daily [21, 29]. Overall, mifepristone is well 
tolerated, and most side effects are associated with continuous use of over 200 mg daily. 
 
 
2.4 
Rationale 
 
Nab-paclitaxel is a relatively effective and well tolerated therapy for MBC. Unfortunately, 
many tumors do not respond, and those that do eventually develop resistance, so improved 
approaches for increasing tumor sensitivity to taxanes are needed. Glucocorticoid-mediated 
GR activation mediates tumor cell resistance by anti-apoptotic signaling. We hypothesize that 

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GR antagonism with mifepristone prior to the administration of cytotoxic chemotherapy will 
improve the efficacy of nab-paclitaxel by blocking the strong anti-apoptotic signal mediated by 
GR activation via circulating endogenous cortisol levels. 
 
We have previously performed a phase I study of nab-paclitaxel and mifepristone. We studied 
two doses of nab-paclitaxel (100 mg/m2 and 80 mg/m2) in combination with mifepristone (300 
mg) the day prior to and the morning of nab-paclitaxel infusion. Nab-paclitaxel was 
administered on days 1, 8, and 15 of a 28 day cycle and mifepristone was administered on days 
0, 1, 7, 8, 14, and 15 of a 28 day cycle. Neutropenia occurred in many patients at both nab- 
paclitaxel dose levels studied, but was easily managed with dose reduction and/or growth factor 
administration. Additionally, promising efficacy was observed in patients with GR positive 
TNBC, with 4 of 6 patients having a response to therapy (2 complete responses, 2 partial 
responses, 1 stable disease, 1 progressive disease). Based on this promising efficacy we are 
proposing this randomized phase II study. 
 
2.5 
Correlative Studies Background 
 
2.5.1 Pharmacokinetic Studies 
 
CYP2C8 activity is known to be inhibited by mifepristone. CYP2C8 is also known to be 
involved in the metabolism of paclitaxel (and therefore nab-paclitaxel). It is therefore possible 
that paclitaxel levels may be increased with concomitant mifepristone administration. 
 
To expand our understanding of a potential PK interaction between nab-paclitaxel and 
mifepristone, we will perform PK studies in the first 20 patients enrolled at pre-specified “PK 
collecting sites” in the beginning of this randomized phase II trial. Patients in this portion of the 
study will have paclitaxel levels drawn at pre-specified time points (at baseline, and then 15 
mins, 45 mins, 4 hrs, 6 hrs, and 24 hrs after completion of nab-paclitaxel administration). These 
patients will not receive mifepristone or placebo week one; mifepristone or placebo will start 
week two. Paclitaxel levels will be drawn cycle 1/day 1 and cycle 1/day 8. PK results will not 
be required to proceed with the study and assays will not be performed in real time. 
 
 
3. PATIENT SELECTION 
 
3.1 
Eligibility Criteria 
3.1.1 Patients must have histologically or cytologically confirmed breast cancer with stage IV 
or unresectable stage III disease. 
 
3.1.2 Patients must have measurable disease, defined as at least one lesion that can be 
accurately measured in at least one dimension (longest diameter to be recorded for non- 
nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques 
or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. To be considered 
pathologically enlarged and measurable, a lymph node must be ≥15 mm in short axis 
when assessed by CT scan (CT scan slice thickness recommended to be no greater than 
5 mm). See Section 11 for the evaluation of measurable disease. 

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3.1.3 Triple-negative breast cancer (defined as ER and PR <10% positive; HER2 0-1+ by 
IHC or FISH ratio < 2.0) 
3.1.4 Patients may have received adjuvant chemotherapy and up to two prior chemotherapy 
for metastatic or locally recurrent disease. No prior nab-paclitaxel will be allowed. 
Prior mifepristone will be allowed. 
 
3.1.5 Age ≥ 18 years. Because no dosing or adverse event data are currently available on the 
use of Nab-Paclitaxel in combination with Mifepristone in patients < 18 years of age, 
children are excluded from this study, but will be eligible for future pediatric trials. 
 
3.1.6 ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix A). 
 
3.1.7 Patients must have normal organ and marrow function as defined below 
– 
absolute neutrophil count 
> 1,500 cells/mm3. 
– 
platelets 
≥ 100,000/mcL 
– 
hemoglobin 
> 9.0 g/dL 
– 
total bilirubin* 
< 1.5 mg/dL 
– 
alkaline phosphatase 
< 2.5 X ULN 
< 5 X ULN if bone mets are present 
– 
AST and ALT 
< 2.5 ULN 
< 5 X ULN if liver mets are present 
– 
adequate renal function 
creatinine ≤ institutional upper limit of normal OR 
creatinine clearance ≥ 60 mL/min/1.73 m2 for patients 
with creatinine levels above institutional normal. 
– 
INR 
< 1.5 
 
*for patients with Gilbert’s Syndrome, elevated total bilirubin is acceptable provided 
conjugated bilirubin is < 1.5 X ULN 
 
3.1.8 Females of child-bearing potential (defined as a sexually mature woman who (1) has 
not undergone hysterectomy [the surgical removal of the uterus] or bilateral 
oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally 
postmenopausal for at least 24 consecutive months [i.e., has had menses at any time 
during the preceding 24 consecutive months]) must: 
 
Either commit to true abstinence* from heterosexual contact (which must be reviewed 
on a monthly basis), or agree to use, and be able to comply with, effective contraception 
without interruption, 28 days prior to starting IP therapy (including dose interruptions), 
and while on study medication or for a longer period if required by local regulations 
following the last dose of IP; and 
 
Have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing 
pregnancy testing during the course of the study, and after the end of study therapy. 
This applies even if the subject practices true abstinence* from heterosexual contact. 

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3.1.9 Male subjects must practice true abstinence* or agree to use a condom during sexual 
contact with a pregnant female or a female of childbearing potential while participating 
in the study, during dose interruptions and for 6 months following protocol 
discontinuation, even if he has undergone a successful vasectomy. * True abstinence is 
acceptable when this is in line with the preferred and usual lifestyle of the subject. 
[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) 
and withdrawal are not acceptable methods of contraception]. 
 
3.1.10 Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE). 
 
3.1.11 Ability to understand and the willingness to sign a written informed consent document. 
 
3.2 
Exclusion Criteria 
 
3.2.1 Patients who are receiving any other investigational agents. 
 
3.2.2 Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering 
the study or those who have not recovered from adverse events due to agents 
administered more than 4 weeks earlier. 
 
3.2.3 Patients with a “currently active” second malignancy other than non-melanoma skin 
cancers. Patients are not considered to have a “currently active” malignancy if they 
have completed therapy and are free of disease for ≥ 3 years. 
 
3.2.4 Patients with known brain metastases will be eligible as long as they have completed 
radiation to the brain, and have been off of corticosteroid therapy for at least 7 days. 
 
3.2.5 History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to mifepristone or paclitaxel/nab-paclitaxel. Patients with a history of mild 
infusion reactions with paclitaxel who were able to continue to receive paclitaxel with 
corticosteroid premedication will be eligible to participate, as these cases were likely 
related to cremaphor and not paclitaxel. 
 
3.2.6 Mifepristone can both inhibit CYP3A4 and induce CYP3A4. Addition of mifepristone 
to a pre-existing drug regimen may cause a mild and temporary increase in plasma drug 
concentration of drugs with significant CYP3A4 metabolism. Medications that are 
strong inducers of CYP3A4 such as carbamazepine, oxcarbazepine, phenobarbital, 
phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John's Wort may decrease 
plasma mifepristone levels. Strong CYP3A4 inhibitor medications are expected to 
cause the largest increases in plasma mifepristone concentrations. 
 
Mifepristone may increase the plasma drug concentration of concomitant medications 
with metabolism mediated by CYP2C9/CYP2C8. Drugs with the largest increases will 
be those whose metabolism is largely or solely mediated by CYP2C9/2C8 and include: 
Non-steroidal Anti-inflammatory drugs (NSAIDs) and warfarin. 
 
For a complete list of concomitant medication restrictions, please see Appendix C. 

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3.2.7 Uncontrolled intercurrent illness including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 
arrhythmia, or psychiatric illness/social situations that would limit compliance with 
study requirements. 
 
3.2.8 Pregnant women are excluded from this study because mifepristone is an abortifacient 
agent with the potential for teratogenic effects. 
 
3.2.9 Because there is an unknown but potential risk for adverse events in nursing infants 
secondary to treatment of the mother with mifepristone, breastfeeding should be 
discontinued if the mother wishes to participate in this study. 
 
3.2.10 HIV-positive patients on combination antiretroviral therapy are ineligible because of the 
potential for pharmacokinetic interactions with mifepristone. In addition, these patients 
are at increased risk of lethal infections when treated with marrow-suppressive therapy. 
Appropriate studies will be undertaken in patients receiving combination antiretroviral 
therapy when indicated. 
 
3.2.11 No history of long-term use of corticosteroids or concurrent short term use of 
corticosteroids is allowed. 
 
 
4. REGISTRATION PROCEDURES 
 
4.1 
General Guidelines 
 
Prior to registration, all patients must have given written informed consent for the 
study. Patients must meet all of the eligibility requirements listed in Section 3. Eligible 
patients will be entered on study centrally by the University of Chicago study 
coordinator. All sites should call the study coordinator at (773) 834-1746 or 
PhaseIICRA@medicine.bsd.uchicago.edu to verify availability of a slot. 
 
Following registration, patients should begin protocol treatment within 7 business days. 
Issues that would cause treatment delays should be discussed with the Lead Principal 
Investigator. If a patient does not receive protocol therapy following registration, the 
patient’s registration on the study will be canceled. The study coordinator/CRA should 
be notified of cancellations as soon as possible. 
 
4.2 
Registration Process 
 
When a potential patient has been identified, notify the University of Chicago Phase II 
CRA via phone or email to ensure a reservation on the study ((773) 834-1746 or 
PhaseIICRA@medicine.bsd.uchicago.edu). Reservations for potential subjects will only 
be held for subjects who have signed consent for that particular study. 
 
When registering a subject, the following must occur: 

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• Confirm that the institution has a current IRB approval letter for the correct version 
of protocol/consent and has an annual update on file, if appropriate. 
• Submit all required materials (Eligibility Checklist, Source documentation, & 
signed consent form) to confirm eligibility and required pre-study procedures to the 
CRA a minimum of 48 hours prior to the subject’s scheduled therapy start date. 
• Source documentation includes copies of all original documents that support each 
inclusion/exclusion criteria. The eligibility checklist does not serve as source 
documentation but rather as a checklist that original source documentation exists for 
each criterion. 
• Communicate with the CRA to ensure all necessary supporting source documents 
are received and the potential subject is eligible to start treatment on schedule. If 
there are questions about eligibility, the CRA will discuss it with the PI. PI may 
clarify, but not overturn, eligibility criteria. 
• Affiliate sites must confirm registration of subjects by obtaining a subject study ID 
number from the CRA via phone, fax or email. 
• If a subject does not start on the scheduled day 1 treatment date, promptly inform 
the CRA as the delay in start may deem the subject ineligible and/or require further 
or repeat testing to ensure eligibility. 
• The date the patient is randomized will be considered the patient’s “On Study 
Date.” The patient’s subject ID will be assigned and a confirmation of registration 
will be issued by the CRA on this date. Subjects that sign consent and do not go 
“OnStudy” will be recorded in the database with the date they signed consent and 
the reason for not going “OnStudy” (e.g., Ineligible, Screen Failure or Withdrawn 
Consent). 
 
4.3 
Blinding Procedure 
 
For each dose level, patients will be randomized in a 1:1 fashion to receive nab- 
paclitaxel with mifepristone or placebo. The randomization sequences will be 
generated by the lead statistician and uploaded into REDCap. The investigational 
drug pharmacist at each site will then be able to randomize patients who have 
signed consent to participate in the study. Only the investigational drug pharmacy 
will be aware of patient’s randomization status. Treating physicians, nurses, clinical 
research assistants, and patients will be blinded to assignment. 
 
4.4 
Unblinding Procedure 
 
Patients will be unblinded if they experience a toxicity that the treating investigator 
feels warrants unblinding. The Treating Investigator will need to contact the Lead 
Site to obtain permission for unblinding. The Treating Investigator should contact 
the Lead Site at PhaseIICRA@medicine.bsd.uchicago.edu requesting unblinding 
and the reason for the unblinding. If unblinding is approved, the treating 
investigator will contact their IDS pharmacist to obtain the treatment assignment. 

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5. TREATMENT PLAN 
 
5.1 
Agent Administration 
 
Treatment will be administered on an outpatient basis. Appropriate dose modifications are 
described in Section 6. Reported adverse events and potential risks are described in Section 8. 
No investigational or commercial agents or therapies other than those described below may be 
administered with the intent to treat the patient's malignancy. 
 
72 patients will be enrolled. All patients will receive nab-paclitaxel 100 mg/m2 on days 1, 8 
and 15 of each 28 day cycle. 36 patients will be randomized to receive placebo and 36 patients 
will be randomized to receive mifepristone 300 mg daily for one day prior to and the day of 
each dose of nab-paclitaxel. 
 
PK studies will be performed in the first 20 patients enrolled at pre-specified “PK collecting 
sites.” Patients in this portion of the study will have paclitaxel levels drawn at the following 
time points: at baseline, and then 15 mins, 45 mins, 4 hrs, 6 hrs, and 24 hrs after completion of 
nab-paclitaxel infusion. These patients will not receive mifepristone or placebo week one; 
mifepristone or placebo will start cycle 1, week 2. Paclitaxel levels will be drawn cycle 1/day 
1-2 and cycle 1/day 8-9. 
 
Regimen Description 
Agent 
Premedications; 
Precautions 
Dose 
Route 
Schedule 
Cycle 
Length 
Nab- 
Paclitaxel 
Patients do not 
require 
premedication prior 
to Nab-Paclitaxel 
administration, as 
hypersensitivity 
reactions are rare. 
100 mg/m2 in 
250 ml NS 
IV over 30 
minutes 
Day 1 
Day 8 
Day 15 
28 days 
(4 
weeks) 
Mifepristonex Take with food. 
300 mg tablet 
PO in the a.m. 
on day prior 
and day of Nab- 
Paclitaxel 
administration 
Days 0 
and 1 
Days 7 
and 8 
Days 14 
and 15 
x – The first 20 patients enrolled at the pre-specified “PK sites” will not receive mifepristone 
for cycle 1, week 1. Mifepristone or placebo will start with cycle 1, week 2 for these patients. 
 
The patient will be requested to maintain a medication diary of each dose with the time of self- 
administration of mifepristone. The medication diary will be returned to clinic staff at the end 
of each cycle. 

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5.2 
General Concomitant Medication and Supportive Care Guidelines 
 
Because there is a potential for interaction of mifepristone with other concomitantly 
administered drugs through the cytochrome P450 system, the case report form must capture the 
concurrent use of all other drugs, over-the-counter medications, or alternative therapies. Both 
the Lead Site as well as the site Principal Investigator should be alerted if the patient is taking 
any agent known to affect (or with the potential to affect) selected CYP450 isoenzymes. 
 
Mifepristone inhibits CYP3A4 and induces CYP3A4. Addition of mifepristone to a pre- 
existing drug regimen may cause a mild and temporary increase in plasma drug concentration 
of drugs with significant CYP3A4 metabolism. Medications that are strong inducers of 
CYP3A4 such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, 
rifabutin, rifampin, rifapentine, St. John's Wort may decrease plasma mifepristone levels. 
Strong CYP3A4 inhibitor medications are expected to cause the largest increases in plasma 
mifepristone concentrations. Mifepristone may increase the plasma drug concentration of 
concomitant medications with metabolism mediated by CYP2C9/2C8. A complete list of drug 
prohibited on study and those which require close monitoring is provided in Appendix C. 
 
Mifepristone is subject to a significant food effect and therefore must be taken with food. 
 
 
5.3 
Duration of Therapy 
In the absence of treatment delays due to adverse event(s), treatment may continue until one of 
the following criteria applies: 
 
• Disease progression 
• Intercurrent illness that prevents further administration of treatment 
• Unacceptable adverse event(s) 
• Patient decides to withdraw from the study 
• General or specific changes in the patient's condition render the patient 
unacceptable for further treatment in the judgment of the Treating Investigator 
• Patient refusal 
• Lost to follow-up/non-compliance 
• Study termination 
 
5.4 
Duration of Follow Up 
Seventy-two total patients (36 per arm) will be enrolled over 24 months, with a 12 month 
follow-up period after the last patient has been enrolled. 

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5.5 
Criteria for Removal from Study 
Patients will be removed from study when any of the criteria listed in Section 5.3 applies. The 
reason for study removal and the date the patient was removed must be documented in the Case 
Report Form. 
 
6. DOSING DELAYS/DOSE MODIFICATIONS 
General guidelines 
• Chemotherapy may be delayed on day 1 
• If chemotherapy is skipped on days 8 and/or 15, these doses are not made up. Drug 
dose reductions are permanent. Once reduced the dose may not be dose escalated 
• If chemotherapy dose reduction below dose level -3 is required for toxicity, 
permanently discontinue study treatment. 
• If chemotherapy is delayed or skipped for > 4 weeks for any reason, permanently 
discontinue study treatment. 
• If chemotherapy is held, mifepristone should also be held (although in many instances 
mifepristone may already have been taken). 
• Mifepristone dose will remain at 300 mg. Mifepristone dose may be skipped or 
permanently discontinued for toxicity, but the dose is not reduced 
 
If mifepristone is skipped for > 4 weeks, permanently discontinue mifepristone. If 
mifepristone is permanently discontinued or skipped for toxicity, continue chemotherapy 
unless otherwise specified below 
 
6.1 
Nab-paclitaxel dose modifications 
 
Dose Level 
Nab-paclitaxel Dose 
(mg/m2) 
0 
100 
-1 
80 
-2 
60 
-3 
60 (every other week) 
 
Event 
Dose Modification 
Neutropenia 
> 1,000/mm3 
No dose modification is required. 
<1000/mm3 
1st occurrence: Delay until ANC > 1000 and reduce 
dose permanently by 1 level with next dose. 
2nd occurrence: Delay until ANC > 1000 and reduce 
dose permanently by 1 level with next dose. 
3rd occurrence: Delay until ANC > 1000. Reduce 
frequency to every other week dosing with next dose 
and initiate G-CSF. 

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If patient continues to have neutropenia despite 
institution of G-CSF and 3 dose modifications, 
protocol therapy should be discontinued permanently 
Thrombocytopenia 
> 100,000/mm3 
No dose modification is required 
75,000-99,999/mm3 
1st occurrence: No dose modification is required. 
Subsequent occurrence: Chemotherapy should be 
reduced by one dose level (maximum of 3 dose 
reductions allowed) for all subsequent doses 
<  75,000 
Delay dose until platelets > 75,000/ mm3. 
Decrease dose by one level for all subsequent doses 
(maximum of 3 dose reductions allowed) 
Hypersensitivity Reaction 
Grade 1 
No dose modification required 
Grade 2 
No dose modification required. 
Add Benadryl and H2 blocker with subsequent cycles. 
Grade 3 
Permanently discontinue chemotherapy. 
Grade 4 
Permanently discontinue chemotherapy. 
Hepatotoxicity 
Grade 1 
No dose modification is required. 
Grade 2 
Decrease dose by one dose level. 
Grade 3 
Hold until improves to grade 1. 
Decrease by one dose level for all subsequent doses. 
Grade 4 
Discontinue chemotherapy permanently. 
Hepatotoxicity 
Grade 1 
No dose modification is required. 
Grade 2 
Decrease dose by one dose level. 
Grade 3 
Hold until improves to grade 1. 
Decrease by one dose level for all subsequent doses. 
Grade 4 
Discontinue chemotherapy permanently. 
Peripheral Neuropathy 
Grade 1 
No dose modification is required. 
Grade 2 
Hold until neuropathy improves to grade 1. 
Decrease dose level by one (maximum of two dose 
reductions allowed). 
Grade 3 
Hold until neuropathy improves to grade 1. 
Decrease dose level by one (maximum of two dose 
reductions allowed). 
Grade 4 
Hold until neuropathy improves to grade 2. 
Decrease dose level by one (maximum of two dose 
reductions allowed). 
Other clinically significant toxicities excluding fatigue, alopecia, hypokalemia, and 
leukopenia 
Grade 1 
No dose modification is required. 
Grade 2 
No dose modification is required. 

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Grade 3 
Hold until toxicity improves to grade 1. Decrease 
dose level by one for all subsequent doses. 
Grade 4 
Discontinue study treatment permanently. 
 
 
6.2 
Mifepristone Dose modification 
 
• Mifepristone dose will remain at 300 mg. Mifepristone dose may be skipped or 
permanently discontinued for toxicity, but the mifepristone dose is not reduced. 
 
• If mifepristone is skipped for > 3 weeks, permanently discontinue mifepristone. 
 
• If patient experiences grade 3 or 4 rash thought to be related to mifepristone, then 
mifepristone will be discontinued permanently. 
 
• If mifepristone is permanently discontinued or skipped for toxicity, continue 
chemotherapy unless otherwise specified as described above. 
 
 
7. ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS 
 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial. A list of 
AEs expected by the investigational agent(s) can be found in Section 8. 
 
7.1 
Adverse Event Characteristics 
• CTCAE term (AE description) and grade: The descriptions and grading scales 
found in the revised NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment 
areas should have access to a copy of the CTCAE version 4.0. A copy of the 
CTCAE version 4.0 can be downloaded from the CTEP web site 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
 
• Attribution of the AE: 
- 
Definite (5) – The AE is clearly related to the study treatment. 
- 
Probable (4) – The AE is likely related to the study treatment. 
- 
Possible (3) – The AE may be related to the study treatment. 
- 
Unlikely (2) – The AE is doubtfully related to the study treatment. 
- 
Unrelated (1) – The AE is clearly NOT related to the study treatment. 
 
7.2 
Adverse Event Definitions 
 
7.2.1 Adverse Event 
 
An adverse event is any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product that does not necessarily 
have a causal relationship with the treatment. An adverse event can be any unfavorable 
and unintended sign (including a laboratory finding), symptom or disease temporally 

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associated with the use of a medicinal (investigational) product, whether or not related 
to the medicinal (investigational) product. 
 
At each evaluation patients should be interviewed in a non-directed manner to elicit 
potential adverse reactions from the patient. The occurrence of an adverse event will be 
based on changes in the patient’s physical examination, laboratory results, and/or signs 
and symptoms, and review of the patient’s own record of adverse events. 
 
Adverse events will be followed until resolution while the patient remains on-study. 
Once the patient is removed from study, events thought to be related to the study 
medication will be followed until resolution or stabilization of the adverse event, or 
until the patient starts a new treatment regimen, or death, whichever comes first. 
Subjects will be followed for AEs/SAEs from the time the informed consent is signed to 
30 days after their last dose of study drug(s). 
 
7.2.2 Pregnancies 
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless 
of age or disease state) of a female subject occurring while the subject is on study 
related therapy, or within (6 months from the subject’s last dose of study related 
therapy), are considered immediately reportable events. Study related therapy is to be 
discontinued immediately. The pregnancy, suspected pregnancy, or positive pregnancy 
test must be reported to the Lead Site immediately at 
PhaseIICRA@medicine.bsd.uchicago.edu, The female subject should be referred to an 
appropriate healthcare professional for further evaluation. 
 
The Treating Investigator will follow the female subject until completion of the 
pregnancy, and must notify the Lead Site at PhaseIICRA@medicine.bsd.uchicago.edu 
about the outcome of the pregnancy (either normal or abnormal outcome). 
 
If the outcome of the pregnancy was abnormal (e.g., spontaneous or therapeutic 
abortion), the Treating 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 the Lead Site at PhaseIICRA@medicine.bsd.uchicago.edu, within 24 hours of the 
Treating Investigator’s knowledge of the event. 
 
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 Treating 
Investigator suspects is related to the in utero exposure to the study related therapy 
should also be reported to the Lead Site at PhaseIICRA@medicine.bsd.uchicago.edu, 
within 24 hours of the Treating Investigator’s knowledge of the event. 
 
Male Subjects: If a female partner of a male subject taking study based therapy 
becomes pregnant, the male subject taking study related therapy should notify the 
Treating Investigator, and the pregnant female partner should be advised to call their 
healthcare provider immediately. Male patients treated with nab-paclitaxel are advised 
not to father a child during and up to 6 months after treatment. 

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7.2.3 Overdose 
 
Overdose, as defined for this protocol, refers to nab-paclitaxel dosing only. 
 
On a per dose basis, an overdose is defined as the following amount over the protocol- 
specified dose of nab-paclitaxel assigned to a given patient, regardless of any associated 
adverse events or sequelae. 
PO 
any amount over the protocol-specified dose 
IV 
10% over the protocol-specified dose 
SC 
10% over the protocol-specified dose 
 
On a schedule or frequency basis, an overdose is defined as anything more frequent 
than the protocol required schedule or frequency. 
 
Complete data about drug administration, including any overdose, regardless of 
whether the overdose was accidental or intentional, should be reported to the Lead 
Site at PhaseIICRA@medicine.bsd.uchicago.edu. 
 
7.2.4 Serious Adverse Events 
 
An adverse event is considered serious if it results in ANY of the following outcomes: 
 
1) Death 
2) Life-threatening (e.g. places subject at immediate risk of death, this does not 
include events that might have caused death if they occurred a greater severity) 
3) Results in inpatient hospitalization or prolongation of existing hospitalization 
for ≥ 24 hours 
4) A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
5) A congenital anomaly/birth defect. 
6) An Important Medical Event 
 
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
 
7.2.5 Unexpected Events 
 
Unexpected events are those not listed at the observed specificity or severity in the 
protocol, informed consent, or FDA-approved package insert. An event is considered 
unexpected if it is listed as occurring within the class of drugs or otherwise expected 
from the drug’s pharmacological properties but which has not been previously observed 
with this specific investigational agent. 

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7.2.6 Adverse Reactions 
 
An adverse event is considered to be an adverse reaction if there evidence to suggest a 
causal relationship to the study agent. This may include a single occurrence of an event 
strongly associated with drug exposure (e.g. Stevens-Johnson Syndrome), one or more 
occurrence of an event otherwise uncommon is the study population, or an aggregate 
analysis of specific events occurring at greater than expected frequency. 
 
7.2.7 Adverse Events of Special Interest (AESIs) 
AESIs are defined as any of the following events, irrespective of the level of severity: 
• endometrial hyperplasia and/or vaginal bleeding 
• retinopathy 
• major adverse cardiovascular events (MACE) which include death related to 
coronary or cerebrovascular disease, acute myocardial infarction, stroke, and 
revascularization (coronary or cerebral) 
 
7.3 
Adverse Event Reporting Requirements 
 
7.3.1 Routine Serious Adverse Event Reporting 
 
All Adverse Events must be reported in routine study data submissions. SAEs 
reported using the Serious Event Reporting Form and/or MedWatch Form 
discussed below must also be reported in routine study data submissions. 
 
All adverse events (except grade 1 and 2 laboratory abnormalities that do not require an 
intervention), regardless of causal relationship, are to be recorded in the case report 
form and source documentation. The Treating Investigator must determine the intensity 
of any adverse events according to the NCI Common Terminology Criteria for Adverse 
Events (CTCAE) Version 4.0 and their causal relationship. 
7.3.2 Serious Adverse Event Reporting to the Coordinating Center 
 
Use the UC CCC protocol number and the protocol-specific patient ID assigned during 
trial registration on all reports. 
 
All serious adverse events and all adverse events of special interest (AESIs) [as defined 
in sections 7.2.4 and 7.2.7] occurring on this study require reporting to the University of 
Chicago Comprehensive Cancer Center (UCCCC). The responsible Research Nurse or 
other designated individual at the treating site should report the SAE/AESI to the Study 
Lead Investigator, the University of Chicago CRA and the CCTO by the end of the 
business day when s/he becomes aware of the event. Events occurring after business 
hours should be reported to the CCTO by 12pm (noon) the next business day. Please 
scan and send via email (preferred) or fax to the following: 
 
University of Chicago Phase II CRA: 
PhaseIICRA@medicine.bsd.uchicago.edu 
Phone: 773-834-1746 
Fax: 773-702-4889 

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UC CCC Cancer Clinical Trials Office Quality Assurance: 
qaccto@bsd.uchicago.edu 
 
All unexpected adverse reactions must be reported to the IND holder so that the 
University of Chicago CCTO can inform the FDA. The responsible Research Nurse or 
other designated individual at the treating site should provide a complete written report 
using the FDA MedWatch 3500A form. The completed form should be sent to the 
CCTO at qaccto@bsd.uchicago.edu and to the Phase II CRA at 
PhaseIICRA@medicine.bsd.uchicago.edu within the specified timelines above 
regardless of whether all information regarding the event is available. If applicable, a 
follow-up report should be provided to the CCTO if additional information on the event 
becomes available. 
 
Participating sites should not forward any adverse event reports directly to the FDA. 
The CCTO will report all events to the FDA as per the current FDA guidelines. 
 
 
All serious adverse events should also be reported to the local IRB of record according 
to their policies and procedures. 
 
7.3.3 Serious and Unexpected Adverse Event reporting by the Coordinating Center 
 
The designated UC CCC Regulatory Manager will notify all participating sites of all 
unexpected and serious adverse reactions that occur on this clinical trial and which are 
reported to the FDA and/or UC Institutional Review Board (IRB). 
All serious and/or unexpected adverse drug experiences, and all adverse events of 
special interest (AESIs) that occur during the course of the study shall be reported to 
Corcept by the Lead Site. The Lead Site will notify Corcept each time that a "follow 
up" report is made to the IRB. 
. 
 
8. PHARMACEUTICAL INFORMATION 
 
8.1 
Investigational Agent Description and Management: Mifepristone 
 
8.1.1 
Product description: Mifepristone and placebo tablets will be provided 
by Corcept Therapeutics in 300 mg tablets. 
 
8.1.2 
Storage requirements: Store at controlled room temperature, 25°C; 
excursions permitted to 15 to 30°C. When stored under these conditions, 
the shelf-life of mifepristone is at least 30 months. 
 
8.1.3 
Route of administration: Oral 
 
8.1.4 
Adverse effects: 
 
Central nervous system: headache, dizziness, fatigue, insomnia, anxiety 

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Cardiovascular: syncope 
Dermatologic: rash 
Gastrointestinal: abdominal pain, nausea, vomiting, diarrhea, dyspepsia 
 
Genitourinary: uterine cramping, uterine hemorrhage, vaginitis, pelvic 
pain 
 
Hematologic: anemia, neutropenia, leukopenia 
Neuromuscular: back pain, rigors, leg pain, weakness 
Respiratory: dyspnea 
Other: hypokalemia, sinusitis, nasopharyngitis 
 
8.2 
Commercial Agent: Nab-paclitaxel (Abraxane) 
 
8.2.1 
Product description: Nab-paclitaxel is commercially available in single- 
dose vials. Each single-use 50 mL vial contains paclitaxel (100mg) and 
approximately 900 mg of human albumin as a stabilizer. Each vial is 
supplied as a white to off-white sterile lyophilized powder. 
 
8.2.2 
Solution preparation: Each vials of nab-paclitaxel lyophilized powder is 
reconstituted in 20 mL of 0.9 NS. 
 
8.2.3 
Storage requirements: Un-reconstituted nab-paclitaxel should be stored 
at 20-25oC in its carton. Reconstituted nab-paclitaxel should be used 
immediately. If not used immediately, the vial must be place in its 
carton and stored at 2-8 oC for a maximum of 8 hours. Both forms 
should be stored in an area free of environmental extremes and must be 
accessible only to study personnel. 
 
8.2.4 
Route of administration: Nab-paclitaxel is injected into a vein 
[intravenous (I.V.) infusion] over 30 minutes. Following administration, 
the intravenous line should be flushed with sodium chloride 9 mg/ml 
(0.9%) solution for injection to ensure complete administration of the 
complete dose, according to local practice. 
 
8.2.5 
Adverse effects 
 
Cardiovascular: ECG abnormalities, edema, hypotension, chest pain, 
cardiac arrest, supraventricular tachycardia, thrombosis, 
thromboembolism 
 
Dermatologic: alopecia 

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Gastrointestinal: nausea, diarrhea, vomiting, mucositis 
 
Hematologic: neutropenia, anemia, myelosuppression, bleeding, 
neutropenic fever 
 
Hepatic: increase in liver function tests 
 
Neuromuscular: sensory neuropathy, weakness, myalgias, arthralgias 
Ocular: visual disturbance 
Renal: elevation in creatinine 
Respiratory: dyspnea, cough 
Other: infection, hypersensitivity reaction 
 
8.2.6 
Drug distribution 
 
Mifepristone ordering information will be provided in the laboratory 
manual. 
 
 
9. BIOMARKER, CORRELATIVE, AND SPECIAL STUDIES 
 
9.1 
Glucocorticoid Receptor (GR) expression in tumor tissue 
 
Patients must have tumor block or slides available for testing, and tumor must be 
glucocorticoid receptor positive (defined as GR > 10% moderate to strongly 
positive by central lab) as determined by central CLIA lab. 
 
Fifteen (15) unstained sections of primary tumor or metastatic tumor or both will be 
requested for each patient enrolled on study. Sections should be 3-5 microns in 
thickness and mounted on positively charged slides. Fine needle aspirates or other 
alternative cytology samples are not acceptable. Slides should be sent accompanied 
by the tumor sample submission form and the de-identified original pathology 
report as per the laboratory manual and sent to: 
 
QualTek Clinical Laboratories 
6483 Calle Real, Suite A 
Goleta, CA 93117 
 
9.2 
Pharmacokinetic Studies 

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To expand and follow up on our understanding of a potential PK interaction 
between nab-paclitaxel and mifepristone, we will perform PK studies in the first 20 
patients enrolled at pre-specified “PK sites”. 
 
Patients in this portion of the study will have paclitaxel levels drawn at pre- 
specified time points (at baseline, and then 15 mins, 45 mins, 4 hrs, 6 hrs, and 24 
hrs after completion of nab-paclitaxel administration). These patients will not 
receive mifepristone or placebo during cycle one week one; mifepristone or placebo 
will start cycle one week two. Paclitaxel levels will be drawn cycle 1/day 1-2 and 
cycle 1/day 8-9. 
 
For paclitaxel levels being collected at the University of Chicago: blood will be 
drawn in 10 ml heparin vacutainers (green tops) to be spun down immediately 
after collection at 3000xg for 15 minutes in a refrigerated centrifuge at 4°C. 
Plasma will then be transferred to two cryovials and stored at -80°C. Plasma 
samples will be labeled with patient’s initials and ID number, protocol 
number, initials of phlebotomist, and sample ID (i.e. D1 baseline, D2 24 hrs, etc). 
Actual blood sampling times will be noted for each patient on the pharmacokinetic 
sample collection form. Any delay or problems will be carefully noted under 
comments along with the initials of the phlebotomist. 
 
Samples drawn at UC will be stored in the BioFluids Core Facility (AB201 & 
AB204, Billings) prior to transfer on dry ice to the Pharmacology Core (KCBD 
7160). 
 
For paclitaxel levels collected at a site other than University of Chicago: blood will 
be drawn in 10 ml heparin vacutainers (greentops) to be spun down immediately 
after collection at 3000xg for 15 minutes in a refrigerated centrifuge at 4°C. Plasma 
will then be transferred to two cryovials and stored at -80°C. Samples will be 
labeled with patient’s initials and ID number, protocol number, initials of 
phlebotomist, and sample ID (i.e. D1 baseline, D2 24 hrs, etc). Actual blood 
sampling times will be noted for each patient on the sample collection form. Any 
delay or problems will be carefully noted under comments along with the initials of 
the phlebotomist. Samples from the same patient will be batched and shipped 
together, accompanied by completed pharmacokinetic sample collection forms for 
each sample. 
 
Patient samples should be shipped frozen on dry ice accompanied by the PK sample 
submission form by an overnight delivery service as per the laboratory manual. 
 
 
10. STUDY CALENDAR 
Baseline evaluations are to be conducted within 14 days prior to start of protocol therapy. 
Scans and x-rays must be done < 4 weeks prior to the start of therapy. In the event that the 
patient’s condition is deteriorating, laboratory evaluations should be repeated within 48 hours 
prior to initiation of the next cycle of therapy. 

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Pre- 
Study 
Cycle 1 
Cycle 2 
and 
beyondf 
Off Studyb 
Day 
0 
Day 
1 
Day 
7 
Day 
8 
Day 
14 
Day 
15 
Mifepristonea 
X 
X 
X 
X 
X 
X 
Nab-paclitaxel 
X 
X 
X 
Informed consent 
X 
Demographics 
X 
Medical history 
X 
Concurrent meds 
X 
X --------------------------------------------------------------------------------- X 
Physical exam 
X 
X 
X 
Vital signs 
X 
X 
X 
X 
X 
Height 
X 
Weight 
X 
X 
X 
X 
X 
Performance status 
X 
X 
X 
CBC w/diff, plts 
X 
X 
X 
X 
X 
Serum chemistryc 
X 
X 
X 
X 
X 
Adverse event evaluation 
X --------------------------------------------------------------------------------- X 
X 
Tumor measurements 
X 
Tumor measurements are repeated every 8 weeks (2 cycles). 
Documentation (radiologic) must be provided for patients removed from 
study for progressive diseasee. 
Xb 
Radiologic evaluation 
X 
Radiologic measurements should be performed every 8 weeks (2 cycles). 
Xb 
B-HCG 
Xd 
TSH 
X 
Serum cortisol 
X 
Tissue collection 
X 
a: First 20 patients enrolled at pre-specified “PK sites” will not receive mifepristone or placebo for cycle 1, week 1. 
They will start study drug or placebo for cycle 1, week 2. 
b: 
Off-study evaluation. 
c: 
Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, potassium, 
total protein, SGOT [AST], SGPT [ALT], sodium. 
d: 
Serum pregnancy test (women of childbearing potential). 
e: 
After 4 cycles of therapy, imaging can be spaced out to every 3rd cycle if treating physician feels it is clinically 
appropriate. 
f: 
After cycle 1 of therapy, the treating physician does have flexibility for scheduling treatment days (ie, a two day 
window for the weekly treatment or omission of a week if needed). 

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11. MEASUREMENT OF EFFECT 
 
11.1 
Antitumor Effect – Solid Tumors 
 
For the purposes of this study, patients should be re-evaluated for response every 8 weeks (2 
cycles). 
 
Response and progression will be evaluated in this study using the new international criteria 
proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline 
(version 1.1) [Eur J Ca 45:228-247, 2009]. Changes in the largest diameter (unidimensional 
measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph 
nodes are used in the RECIST criteria. 
 
11.1.1 Definitions 
 
Evaluable for toxicity. All patients will be evaluable for toxicity from the time of their 
first treatment with mifepristone. 
 
Evaluable for objective response. Only those patients who have measurable disease 
present at baseline, have received at least one cycle of therapy, and have had their 
disease re-evaluated will be considered evaluable for response.  These patients will 
have their response classified according to the definitions stated below. (Note: Patients 
who exhibit objective disease progression prior to the end of cycle 1 will also be 
considered evaluable.) 
 
Evaluable Non-Target Disease Response. Patients who have lesions present at baseline 
that are evaluable but do not meet the definitions of measurable disease, have received 
at least one cycle of therapy, and have had their disease re-evaluated will be considered 
evaluable for non-target disease. The response assessment is based on the presence, 
absence, or unequivocal progression of the lesions. 
 
11.1.2 Disease Parameters 
 
Measurable disease. Measurable lesions are defined as those that can be accurately 
measured in at least one dimension (longest diameter to be recorded) as ≥20 mm by 
chest x-ray or as ≥10 mm with CT scan, MRI, or calipers by clinical exam. All tumor 
measurements must be recorded in millimeters (or decimal fractions of centimeters). 
 
Note: Tumor lesions that are situated in a previously irradiated area will be considered 
measurable provided they have increased in size following the completion of radiation, 
and that radiation was completed at least 4 weeks in advance of initiating protocol 
therapy. 
 
Malignant lymph nodes. To be considered pathologically enlarged and measurable, a 
lymph node must be ≥15 mm in short axis when assessed by CT scan (CT scan slice 
thickness recommended to be no greater than 5 mm). At baseline and in follow-up, 
only the short axis will be measured and followed. 

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Non-measurable disease. All other lesions (or sites of disease), including small lesions 
(longest diameter <10 mm or pathological lymph nodes with ≥10 to <15 mm short 
axis), are considered non-measurable disease. Bone lesions, leptomeningeal disease, 
ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory 
breast disease, and abdominal masses (not followed by CT or MRI), are considered as 
non-measurable. 
 
Note: Cystic lesions that meet the criteria for radiographically defined simple cysts 
should not be considered as malignant lesions (neither measurable nor non-measurable) 
since they are, by definition, simple cysts. 
 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if non- 
cystic lesions are present in the same patient, these are preferred for selection as target 
lesions. 
 
Target lesions. All measurable lesions up to a maximum of 2 lesions per organ and 5 
lesions in total, representative of all involved organs, should be identified as target 
lesions and recorded and measured at baseline. Target lesions should be selected on the 
basis of their size (lesions with the longest diameter), be representative of all involved 
organs, but in addition should be those that lend themselves to reproducible repeated 
measurements. It may be the case that, on occasion, the largest lesion does not lend 
itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected. A sum of the diameters (longest for 
non-nodal lesions, short axis for nodal lesions) for all target lesions will be calculated 
and reported as the baseline sum diameters. If lymph nodes are to be included in the 
sum, then only the short axis is added into the sum. The baseline sum diameters will be 
used as reference to further characterize any objective tumor regression in the 
measurable dimension of the disease. 
 
Non-target lesions. All other lesions (or sites of disease) including any measurable 
lesions over and above the 5 target lesions should be identified as non-target lesions 
and should also be recorded at baseline. Measurements of these lesions are not 
required, but the presence, absence, or in rare cases unequivocal progression of each 
should be noted throughout follow-up. 
 
11.1.3 Methods for Evaluation of Measurable Disease 
 
All measurements should be taken and recorded in metric notation using a ruler or 
calipers. All baseline evaluations should be performed as closely as possible to the 
beginning of treatment and never more than 4 weeks before the beginning of the 
treatment. 
 
The same method of assessment and the same technique should be used to characterize 
each identified and reported lesion at baseline and during follow-up. Imaging-based 
evaluation is preferred to evaluation by clinical examination unless the lesion(s) being 
followed cannot be imaged but are assessable by clinical exam. 

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Clinical lesions. Clinical lesions will only be considered measurable when they are 
superficial (e.g., skin nodules and palpable lymph nodes) and ≥10 mm diameter as 
assessed using calipers (e.g., skin nodules). In the case of skin lesions, documentation 
by color photography, including a ruler to estimate the size of the lesion, is 
recommended. 
 
Chest x-ray. Lesions on chest x-ray are acceptable as measurable lesions when they are 
clearly defined and surrounded by aerated lung. However, CT is preferable. 
 
Conventional CT and MRI. This guideline has defined measurability of lesions on CT 
scan based on the assumption that CT slice thickness is 5 mm or less. If CT scans have 
slice thickness greater than 5 mm, the minimum size for a measurable lesion should be 
twice the slice thickness. MRI is also acceptable in certain situations (e.g. for body 
scans). 
 
Use of MRI remains a complex issue. MRI has excellent contrast, spatial, and temporal 
resolution; however, there are many image acquisition variables involved in MRI, 
which greatly impact image quality, lesion conspicuity, and measurement. 
Furthermore, the availability of MRI is variable globally. As with CT, if an MRI is 
performed, the technical specifications of the scanning sequences used should be 
optimized for the evaluation of the type and site of disease. Furthermore, as with CT, 
the modality used at follow-up should be the same as was used at baseline and the 
lesions should be measured/assessed on the same pulse sequence. It is beyond the 
scope of the RECIST guidelines to prescribe specific MRI pulse sequence parameters 
for all scanners, body parts, and diseases. Ideally, the same type of scanner should be 
used and the image acquisition protocol should be followed as closely as possible to 
prior scans. Body scans should be performed with breath-hold scanning techniques, if 
possible. 
 
PET-CT. At present, the low dose or attenuation correction CT portion of a combined 
PET-CT is not always of optimal diagnostic CT quality for use with RECIST 
measurements. However, if the site can document that the CT performed as part of a 
PET-CT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast), 
then the CT portion of the PET-CT can be used for RECIST measurements and can be 
used interchangeably with conventional CT in accurately measuring cancer lesions over 
time. Note, however, that the PET portion of the CT introduces additional data which 
may bias an investigator if it is not routinely or serially performed. 
 
Ultrasound. Ultrasound is not useful in assessment of lesion size and should not be 
used as a method of measurement. Ultrasound examinations cannot be reproduced in 
their entirety for independent review at a later date and, because they are operator 
dependent, it cannot be guaranteed that the same technique and measurements will be 
taken from one assessment to the next. If new lesions are identified by ultrasound in 
the course of the study, confirmation by CT or MRI is advised. If there is concern 
about radiation exposure at CT, MRI may be used instead of CT in selected instances. 
 
Tumor markers. Tumor markers alone cannot be used to assess response. If markers 

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are initially above the upper normal limit, they must normalize for a patient to be 
considered in complete clinical response. 
 
Cytology, Histology. These techniques can be used to differentiate between partial 
responses (PR) and complete responses (CR) in rare cases (e.g., residual lesions in 
tumor types, such as germ cell tumors, where known residual benign tumors can 
remain). 
 
The cytological confirmation of the neoplastic origin of any effusion that appears or 
worsens during treatment when the measurable tumor has met criteria for response or 
stable disease is mandatory to differentiate between response or stable disease (an 
effusion may be a side effect of the treatment) and progressive disease. 
FDG-PET While FDG-PET response assessments need additional study, it is 
sometimes reasonable to incorporate the use of FDG-PET scanning to complement CT 
scanning in assessment of progression (particularly possible 'new' disease). New 
lesions on the basis of FDG-PET imaging can be identified according to the following 
algorithm: 
a. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of 
PD based on a new lesion. 
b. No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive 
FDG-PET at follow-up corresponds to a new site of disease confirmed by CT, this 
is PD. If the positive FDG-PET at follow-up is not confirmed as a new site of 
disease on CT, additional follow-up CT scans are needed to determine if there is 
truly progression occurring at that site (if so, the date of PD will be the date of the 
initial abnormal FDG-PET scan). If the positive FDG-PET at follow-up 
corresponds to a pre-existing site of disease on CT that is not progressing on the 
basis of the anatomic images, this is not PD. 
c. FDG-PET may be used to upgrade a response to a CR in a manner similar to a 
biopsy in cases where a residual radiographic abnormality is thought to represent 
fibrosis or scarring. The use of FDG-PET in this circumstance should be 
prospectively described in the protocol and supported by disease-specific medical 
literature for the indication. However, it must be acknowledged that both 
approaches may lead to false positive CR due to limitations of FDG-PET and 
biopsy resolution/sensitivity. 
 
Note: A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an uptake 
greater than twice that of the surrounding tissue on the attenuation corrected image. 
 
11.1.4 Response Criteria 
 
11.1.4.1 
Evaluation of Target Lesions 
 
Complete Response (CR): Disappearance of all target lesions. Any pathological 
lymph nodes (whether target or non-target) must have reduction in short axis to <10 
mm. 
 
Partial Response (PR): At least a 30% decrease in the sum of the diameters of 

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target lesions, taking as reference the baseline sum diameters. 
 
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of 
target lesions, taking as reference the smallest sum on study (this includes the 
baseline sum if that is the smallest on study). In addition to the relative increase of 
20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: 
the appearance of one or more new lesions is also considered progressions). 
 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest sum diameters while on 
study. 
 
11.1.4.2 
Evaluation of Non-Target Lesions 
 
Complete Response (CR): Disappearance of all non-target lesions and 
normalization of tumor marker level. All lymph nodes must be non-pathological in 
size (<10 mm short axis). 
 
Note: If tumor markers are initially above the upper normal limit, they must 
normalize for a patient to be considered in complete clinical response. 
 
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or 
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. Unequivocal progression 
should not normally trump target lesion status. It must be representative of overall 
disease status change, not a single lesion increase. 
 
Although a clear progression of “non-target” lesions only is exceptional, the opinion 
of the treating physician should prevail in such circumstances, and the progression 
status should be confirmed at a later time by the review panel (or Lead Principal 
Investigator). 
 
11.1.4.3 
Evaluation of Best Overall Response 
 
The best overall response is the best response recorded from the start of the 
treatment until disease progression/recurrence (taking as reference for progressive 
disease the smallest measurements recorded since the treatment started). The 
patient's best response assignment will depend on the achievement of both 
measurement and confirmation criteria. 
 
For Patients with Measurable Disease (i.e., Target Disease) 
 
Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response when 
Confirmation is Required* 
CR 
CR 
No 
CR 
>4 wks. Confirmation** 

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CR 
Non-CR/Non- 
PD 
No 
PR 
>4 wks. Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non- 
PD/not 
evaluated 
No 
PR 
SD 
Non-CR/Non- 
PD/not 
evaluated 
No 
SD 
Documented at least once >4 
wks. from baseline** 
PD 
Any 
Yes or No 
PD 
no prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
 
See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
** 
Only for non-randomized trials with response as primary endpoint. 
*** 
In exceptional circumstances, unequivocal progression in non-target lesions may be 
accepted as disease progression. 
Note: Patients with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be 
reported as “symptomatic deterioration.” Every effort should be made to document the 
objective progression even after discontinuation of treatment. 
 
 
11.1.5 Confirmatory Measurement/Duration of Response 
 
Confirmation 
To be assigned a status of PR or CR, changes in tumor measurements must be 
confirmed by repeat assessments that should be performed between 6-8 weeks after the 
criteria for response are first met. In the case of SD, follow-up measurements must have 
met the SD criteria at least once after study entry at a minimum interval of 6 weeks). 
 
Duration of overall response: The duration of overall response is measured from the 
time measurement criteria are met for CR or PR (whichever is first recorded) until the 
first date that recurrent or progressive disease is objectively documented (taking as 
reference for progressive disease the smallest measurements recorded since the 
treatment started). 
 
The duration of overall CR is measured from the time measurement criteria are first met 
for CR until the first date that progressive disease is objectively documented. 
 
Duration of stable disease: Stable disease is measured from the start of the treatment 
until the criteria for progression are met, taking as reference the smallest measurements 
recorded since the treatment started, including the baseline measurements. 
 
11.1.6 Progression-Free Survival 

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PFS is defined as the duration of time from date of randomization to time of 
progression or death, whichever occurs first. 
 
 
12. DATA REPORTING 
 
Data reporting will be performed utilizing the eVelos electronic data capture system. The 
University of Chicago CRA will provide you with the applicable user registration information. 
 
All required data must be recorded in the eVelos database at the completion of each cycle. 
AEs are to be entered in real time. SAEs are to be entered on the Serious Event Form within 
24 hours of the site’s knowledge of the event and sent via email (preferred) or fax to the 
University of Chicago (PhaseIICRA@medicine.bsd.uchicago.edu or 
qaccto@bsd.uchicago.edu; Fax: 773-702-4889). All case report forms must be completed by 
designated study personnel. Each screened (consented) patient is to be entered into eVelos 
within 48 hours of patient registration. In addition to direct data entry, you may be required to 
provide supporting source documentation. Source records are original documents, data, and 
records (e.g., medical records, raw data collection forms, pharmacy dispensing records, 
recorded data from automated instruments, laboratory data) that are relevant to the clinical 
trial. Each site will prepare and maintain adequate and accurate source documents. These 
documents are designed to record all observations and other pertinent data for each subject 
enrolled in this clinical trial. Source records must be adequate to reconstruct all data 
transcribed onto the case report form. 
 
13. STATISTICAL CONSIDERATIONS 
 
13.1 
Study Design/Endpoints 
 
This is a randomized, double-blind, placebo-controlled phase II trial comparing nab-paclitaxel 
plus mifepristone versus nab-paclitaxel plus placebo using progression-free survival (PFS )as 
the primary endpoint. 
 
13.2 
Sample Size/Accrual Rate 
 
Seventy-two total patients (36 per arm) will be enrolled over 12 months, with a 12 month follow-up 
period after the last patient has been enrolled. Assuming 90% of patients are GR+, this is expected 
to yield 64 GR+ patients (32 per arm). The primary objective is to compare progression-free 
survival (PFS) between the two treatment arms in the GR+ subgroup. Internal Celgene data reveals 
that patients with TNBC who received single agent nab-paclitaxel as second-line or greater therapy 
have a PFS of 3.15 months. 
 
The sample size is determined based on the Phase II screening design proposed by Rubinstein et al 
(JCO, 2005). Assuming the monotherapy arm has median PFS of 3.15 months, a sample size of 64 
GR+ patients (n=32 per arm) will achieve 80% power to detect a hazard ratio HR =0.61 using a 
one-sided logrank test with alpha=15% significance level. This calculation assumes 5% annual loss 
to follow-up rate. Hazard ratio HR=0.61 corresponds to the median PFS of 5.18 months in the 
combination arm, and the expected number of events in the two arms is 31 and 28, respectively. 
Descriptive analyses will be conducted in the small number of anticipated GR- patients. 

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13.3 
Stratification Factors 
 
Randomization will be stratified according to the number of prior cytotoxic therapies received 
(0 vs. 1-2) using the method of permuted blocks. When the next patient is to be randomized, 
the UC research coordinator will email the IDS pharmacist at the site where the patient is being 
enrolled and provide the pharmacist with the patient ID number, patient initials, and stratum (0 
vs.1-2 prior therapies). The IDS pharmacist will log in to REDCap to obtain the treatment 
assignment. 
 
13.4 
Analysis of Secondary Endpoints 
 
We will perform PK analysis on the first 20 patients who are enrolled at a PK collection site as 
discussed prior. 
 
13.5 
Reporting and Exclusions 
 
13.5.1 Evaluation of Toxicity 
 
All patients will be evaluable for toxicity from the time of their first treatment. 
 
13.5.2 Evaluation of Response 
 
All patients included in the study must be assessed for response to treatment, even if 
there are major protocol treatment deviations or if they are ineligible. Each patient will 
be assigned one of the following categories: 1) complete response, 2) partial response, 
3) stable disease, 4) progressive disease, 5) early death from malignant disease, 6) early 
death from toxicity, 7) early death because of other cause, or 9) unknown (not 
assessable, insufficient data). [Note: By arbitrary convention, category 9 usually 
designates the “unknown” status of any type of data in a clinical database.] 
 
All of the patients who met the eligibility criteria (with the possible exception of those 
who received no study medication) should be included in the main analysis of the 
response rate. Patients in response categories 4-9 should be considered to have a 
treatment failure (disease progression). Thus, an incorrect treatment schedule or drug 
administration does not result in exclusion from the analysis of the response rate. 
 
All conclusions should be based on all eligible patients. Sub-analyses may then be 
performed on the basis of a subset of patients, excluding those for whom major protocol 
deviations have been identified (e.g., early death due to other reasons, early 
discontinuation of treatment, major protocol violations, etc.). However, these 
subanalyses may not serve as the basis for drawing conclusions concerning treatment 
efficacy, and the reasons for excluding patients from the analysis should be clearly 
reported. The 95% confidence intervals should also be provided. 

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14. 
STUDY MANAGEMENT AND REGULATORY AFFAIRS 
 
14.1 
Multicenter Guidelines 
 
The specific responsibilities of the Lead Principal Investigator and the Coordinating Center are 
presented in Appendix B. Clinical studies coordinated by The University of Chicago must be 
conducted in accordance with the ethical principles that are consistent with Good Clinical 
Practices (GCP) and in compliance with other applicable regulatory requirements 
 
The Study Lead PI/Coordinating Center is responsible for distributing all official protocols, 
amendments, and IND Action Letters or Safety Reports to all participating institutions for 
submission to their individual IRBs for action as required. 
 
14.2 
Institutional Review Board (IRB) Approval and Consent 
 
Unless otherwise specified, each participating institution must obtain its own IRB approval. 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. 
 
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. 
 
14.3 
Food and Drug Administration (FDA) Approval 
 
This study will be conducted under an IND held by Dr. Rita Nanda at the University of 
Chicago. The University of Chicago CCTO will be responsible for facilitating all 
communications with the FDA on behalf of the IND holder. Participating sites should not 
communicate directly with the FDA. 
 
14.4 
Required Documentation 
 
Before the study can be initiated at any site, the following documentation must be provided to 
the Cancer Clinical Trials Office (CCTO) at the University of Chicago Comprehensive Cancer 
Center. 

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• A copy of the official IRB approval letter for the protocol and informed consent 
• IRB membership list 
• CVs and medical licensure for the Site Principal Investigator and any sub-investigators 
who will be involved in the study. 
• Form FDA 1572 appropriately filled out and signed with appropriate documentation 
• CAP and CLIA Laboratory certification numbers and institution lab normal values 
• Investigational drug accountability standard operating procedures 
• Additionally, before the study can be initiated at any site, the required executed research 
contract/subcontract must be on file with the University of Chicago. 
 
14.5 
Data and Safety Monitoring 
This study will be remotely monitored by the designated University of Chicago Clinical 
Research Associate (CRA) in accordance with the University of Chicago, Section of 
Hematology/Oncology standard operating procedure titled Monitoring of Multi-Institutional 
Investigator Initiated Clinical Trials. 
Prior to subject recruitment, and unless otherwise specified, a participating site will undergo a 
Site Initiation Teleconference to be conducted by the designated University of Chicago research 
team. The site’s principal investigator and his or her study staff must attend the site initiation 
meeting. 
 
Monitoring will be conducted to verify the following: 
• Adherence to the protocol 
• Completeness and accuracy of study data and samples collected 
• Compliance with regulations 
• Submission of required source documents 
 
Participating sites will also undergo a site close-out teleconference upon completion, 
termination or cancellation of a study to ensure fulfillment of study obligations during the 
conduct of the study, and to ensure that the Site Investigator is aware of his/her ongoing 
responsibilities. 
Unless otherwise specified, this protocol will undergo weekly review at the multi-institutional 
data and safety monitoring teleconference as per procedures specified by the UC CCC NCI- 
approved Data and Safety Monitoring Plan. The conference will review: 
• Enrollment rate relative to expectations, characteristics of participants 
• Safety of study participants (Serious Adverse Event & Adverse Event reporting) 
• Adherence to protocol (protocol deviations) 
• Completeness, validity and integrity of study data 
• Retention of study participants 
 
Protocol deviations are to be documented using the Protocol Deviation Form and sent via 
email to PhaseIICRA@medicine.bsd.uchicago.edu. Deviations that are considered major 
because they impact subject safety or alter the risk/benefit ratio, compromise the integrity of 
the study data, and/or affect subjects’ willingness to participate in the study must be reported 

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within 7 days. Please contact the University of Chicago CRA 
(PhaseIICRA@medicine.bsd.uchicago.edu) if you have questions about how to report 
deviations. All major protocol deviations should also be reported to the local IRB of record 
according to their policies and procedures. 
 
14.6 
Auditing 
 
In addition to the clinical monitoring procedures, the University of Chicago Comprehensive 
Cancer Center will perform routine Quality Assurance Audits of investigator-initiated clinical 
trials as described in the NCI-approved UC CCC DSM Plan. Audits provide assurance that 
trials are conducted and study data are collected, documented and reported in compliance with 
the protocol. Further, quality assurance audits ensure that study data are collected, documented 
and reported in compliance with Good Clinical Practices (GCP) Guidelines and regulatory 
requirements. The audit will review subjects enrolled at the University of Chicago in accordance 
with audit procedures specified in the UC CCC Data and Safety Monitoring plan. For 
institutions who are formal members of the Personalized Cancer Care Consortium (PCCC), the 
UC CCC will conduct on site quality assurance audits on average every two years during the 
enrollment and treatment phase of the study. 
 
Auditing procedures for participating sites that are not full members of the PCCC must be 
specified and approved by the UC CCC Clinical Research Advisory Committee. In general, for 
sites that are not full members of the PCCC, auditing responsibility will be delegated to the 
participating center, with the annual audit report forwarded to the University of Chicago for 
review. 
 
A regulatory authority (e.g. FDA) may also wish to conduct an inspection of the study, during 
its conduct or even after its completion. If an inspection has been requested by a regulatory 
authority, the site investigator must immediately inform the University of Chicago Cancer 
Clinical Trials Office and Regulatory Manager that such a request has been made. 
 
14.7 
Amendments to the Protocol 
 
All modifications to the protocol, consent form, and/or questionnaires will be submitted to the 
University of Chicago IRB for review and approval. A list of the proposed modifications or 
amendments to the protocol and/or an explanation of the need of these modifications will be 
submitted, along with a revised protocol incorporating the  modifications. Only  the Study 
Lead PI can authorize any modifications, amendments, or termination of the protocol. Once a 
protocol amendment has been approved by the University of Chicago IRB, the Regulatory 
Manager will send the amended protocol and consent form (if applicable) to the affiliate 
institutions electronically. Upon receipt of the packet the affiliate institution is expected to do 
the following: 
 
• The affiliate must reply to the email from the Regulatory Manager indicating that the 
amendment was received by the institution and that it will be submitted to the local IRB. 
 
• The amendment should be submitted to the affiliate institution’s IRB as soon as 
possible after receipt. The amendment must be IRB approved by the institution 

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within 3 months from the date that it was received. 
 
• The University of Chicago  version  date  and/or  amendment  number  must 
appear on the affiliate consent form and on the affiliate IRB approval letter. The 
version dates can be found on the footer of every page of  the protocol and consent  
form. The amendment number can be found on the University of Chicago IRB 
amendment approval letter that is sent with the protocol/amendment mailing. 
 
• The IRB approval for the amendment and the amended consent form (if amended 
consent is necessary) for the affiliate institution must be sent to the designated UC 
Regulatory Manager as soon as it is received. 
 
14.8 
Annual IRB Renewals, Continuing Review and Final Reports 
 
A continuing review of the protocol will be completed by the University of Chicago IRB and 
the participating institutions’ IRBs at least once a year for the duration of the study. The  annual 
IRB renewal approvals for participating institutions should be forwarded promptly to the 
Regulatory Manager. If the institution’s IRB requires  a  new  version  of  the  consent  form 
with the annual renewal, the consent form should be included with the renewal letter. 
 
14.9 
Record Retention 
 
Study documentation includes all CRFs, 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. 
 
14.10 Obligations of Study Site Investigators 
 
The Study Site 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 Study Site Principal Investigator is responsible for personally overseeing the 
treatment of all study patients. He/she 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. 

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The Study Site Principal Investigator at each institution or site will be responsible for assuring 
that all the required data will be collected and entered into the CRFs. Periodically, monitoring 
visits or audits will be conducted and he/she must provide access to original records to permit 
verification of proper entry of data. 

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1. 
Jemal, A., et al., Cancer statistics, 2010. CA Cancer J Clin, 2010. 60(5): p. 277-300. 
2. 
Cardoso, F., et al., Second and subsequent lines of chemotherapy for metastatic breast 
cancer: what did we learn in the last two decades? Ann Oncol, 2002. 13(2): p. 197-207. 
3. 
Seidman, A.D., et al., Randomized phase III trial of weekly compared with every-3- 
weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 
overexpressors and random assignment to trastuzumab or not in HER-2 
nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J 
Clin Oncol, 2008. 26(10): p. 1642-9. 
4. 
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Allergy Immunol, 2003. 24(3): p. 253-62. 
5. 
Abi 007. Drugs R D, 2004. 5(3): p. 155-9. 
6. 
Blum, J.L., et al., Phase II study of weekly albumin-bound paclitaxel for patients with 
metastatic breast cancer heavily pretreated with taxanes. Clin Breast Cancer, 2007. 
7(11): p. 850-6. 
7. 
Conzen, S.D., Minireview: nuclear receptors and breast cancer. Mol Endocrinol, 2008. 
22(10): p. 2215-28. 
8. 
Wu, W., et al., Microarray analysis reveals glucocorticoid-regulated survival genes 
that are associated with inhibition of apoptosis in breast epithelial cells. Cancer Res, 
2004. 64(5): p. 1757-64. 
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Pan, D., M. Kocherginsky, and S.D. Conzen, Activation of the glucocorticoid receptor 
is associated with poor prognosis in estrogen receptor-negative breast cancer. Cancer 
Res, 2011. 71(20): p. 6360-70. 
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Melhem, A., et al., Administration of glucocorticoids to ovarian cancer patients is 
associated with expression of the anti-apoptotic genes SGK1 and MKP1/DUSP1 in 
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Skor, M.N., et al., Glucocorticoid receptor antagonism as a novel therapy for triple- 
negative breast cancer. Clin Cancer Res, 2013. 19(22): p. 6163-72. 
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Spitz, I.M. and C.W. Bardin, Mifepristone (RU 486)--a modulator of progestin and 
glucocorticoid action. N Engl J Med, 1993. 329(6): p. 404-12. 
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Nieman, L.K., et al., Successful treatment of Cushing's syndrome with the 
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Pomara, N., et al., Mifepristone (RU 486) for Alzheimer's disease. Neurology, 2002. 
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Belanoff, J.K., et al., Slowing the progression of cognitive decline in Alzheimer's 
disease using mifepristone. J Mol Neurosci, 2002. 19(1-2): p. 201-6. 
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Gallagher, P., et al., Effects of adjunctive mifepristone (RU-486) administration on 
neurocognitive function and symptoms in schizophrenia. Biol Psychiatry, 2005. 57(2): 
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65(10-11): p. 825-30. 
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Grunberg, S.M., et al., Treatment of unresectable meningiomas with the 
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Takiyama, Y., H. Tanaka, and I. Makino, The effects of hydrocortisone and RU486 
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APPENDIX A 
PERFORMANCE STATUS CRITERIA 
ECOG Performance Status Scale 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity. Fully active, able 
to carry on all pre-disease 
performance without restriction. 
100 
Normal, no complaints, no evidence 
of disease. 
90 
Able to carry on normal activity; 
minor signs or symptoms of disease. 
1 
Symptoms, but ambulatory. 
Restricted in physically strenuous 
activity, but ambulatory and able 
to carry out work of a light or 
sedentary nature (e.g., light 
housework, office work). 
80 
Normal activity with effort; some 
signs or symptoms of disease. 
70 
Cares for self, unable to carry on 
normal activity or to do active work. 
2 
In bed <50% of the time. 
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities. Up and about 
more than 50% of waking hours. 
60 
Requires occasional assistance, but 
is able to care for most of his/her 
needs. 
50 
Requires considerable assistance and 
frequent medical care. 
3 
In bed >50% of the time. Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours. 
40 
Disabled, requires special care and 
assistance. 
30 
Severely disabled, hospitalization 
indicated. Death not imminent. 
4 
100% bedridden. Completely 
disabled. Cannot carry on any 
self-care. Totally confined to bed 
or chair. 
20 
Very sick, hospitalization indicated. 
Death not imminent. 
10 
Moribund, fatal processes 
progressing rapidly. 
5 
Dead. 
0 
Dead. 

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APPENDIX B 
MULTICENTER GUIDELINES 
Responsibility of the Study Lead PI 
• The Study Lead PI will be the single liaison with regulatory and data management staff, 
outside sponsor/s, FDA, and funding agencies The Study Lead PI is responsible for the 
coordination, development, submission, and approval of the protocol as well as its 
subsequent amendments. The protocol must not be rewritten or modified by anyone 
other than the Study Lead PI. There will be only one version of the protocol, and each 
participating institution will use that document. The Study Lead PI is responsible for 
assuring that all participating institutions are using the correct version of the protocol. 
• The Study Lead PI is responsible for the overall conduct of the study at all participating 
institutions and for monitoring its progress. All reporting requirements are the 
responsibility of the Study Lead PI. 
• The Study Lead PI is responsible for the timely review of Adverse Events (AE) to 
assure safety of the patients. 
• The Study Lead PI will be responsible for the review of and timely submission of data 
for study analysis. 
 
Responsibilities of the Coordinating Center 
• The Coordinating Center is responsible for maintaining copies of IRB approvals from 
each participating site. 
• The Coordinating Center is responsible for central patient registration. The 
Coordinating Center is responsible for assuring that IRB approval has been obtained at 
each participating site prior to the first patient registration from that site. 
• The Coordinating Center is responsible for the preparation of all submitted data for 
review by the Study Lead PI. 
• The Coordinating Center will maintain documentation of AE reports. The Coordinating 
Center will submit AE reports to the Study Lead PI for timely review. 

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APPENDIX C 
 
CONCOMITANT MEDICATION RESTRICTIONS 
 
CYP3A4 Substrate medications 
Mifepristone inhibits CYP3A4 and induces CYP3A4. The induction of CYP3A4 becomes 
maximal after 7-10 days of dosing. Addition of mifepristone to a pre-existing drug regimen 
may cause a moderate and temporary increase in plasma drug concentration of drugs with 
significant CYP3A4 metabolism. Induction of CYP3A4 by mifepristone is expected to reduce 
plasma concentrations of CYP3A4 substrates after several doses of mifepristone. When a 
concomitant CYP3A4 substrate medication is added onto chronic mifepristone dosing, there 
may be a decrease in plasma drug concentrations of the CYP3A4 substrate. Concomitant 
medications that are subject to the greatest decreases in plasma drug concentration are those 
orally administered drugs with a large first pass metabolism mediated largely or solely by 
CYP3A4. In addition, mifepristone is a substrate for CYP3A4 and strong inhibitors of 
CYP3A4 are expected to increase exposure to mifepristone. 
The following drugs have these characteristics and are not allowed during the study: 
• cyclosporine, tacrolimus, sirolimus 
• HIV protease inhibitors including amprenavir, atazanavir, fosamprenavir, indinavir, 
lopinavir, nelfinavir, saquinavir, ritonavir, tipranavir, darunavir, boceprevir 
• non-nucleoside reverse transcriptase inhibitors including delavirdine, nevirapine, 
efavirenz, etravirine 
• kinase inhibitors including erlotinib, imatinib, sunitinib, nilotinib, dasatinib 
• dihydroergotamine, ergotamine 
• fentanyl 
• pimozide 
• conivaptan 
• itraconazole, voriconazole, posaconazole 
• clarithromycin, telithromycin 
• certain HMG CoA reductase inhibitors (statins): lovastatin, simvastatin, atorvastatin 
• certain benzodiazepines: (midazolam [orally administered], triazolam, alprazolam) 
• Other CYP3A4 substrates although not absolutely prohibited during the study may 
require careful monitoring and/or dose adjustment. These include the following drugs 
or drug classes: 
• Calcium Channel Blockers except amlodipine 
• Phosphodiesterase Type 5 inhibitors (sildenafil, vardenafil, tadalafil) 
• Benzodiazepines (diazepam, clonazepam, chlordiazepoxide, brotizolam, estazolam, 
flunitrazepam, flurazepam, lormetazepam, nimetazepam, nitrazepam, temezepam, 
bromazepam, chlorazepate, prazepam) but not lorazepam or oxazepam 
• Benzodiazepine related hypnotics (zolpidem, zaleplon, eszopiclone) 
• Anti-arrhythmic drugs including amiodarone, quinidine, encainide 
 
Several options are available for managing increases in the levels of concomitant medications 
that are 3A4 substrates during mifepristone therapy: 

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Management during the initial inhibitory phase 
CYP3A4 inhibition occurs and will predominate starting with the first dose of mifepristone 
and will last for 3 to 4 days.  During this time, the acute effects of raised plasma 
concentrations of the concomitant medication may be monitored clinically for lack of 
tolerability by keeping subjects under direct observation for several hours after the first dose of 
mifepristone and the concomitant medication. If the concomitmant medication is not tolerated, 
then therapy should be discontinued, or the dose lowered to the minimal dose. Alternatively, 
the concomitant medication may be stopped for several days and reintroduced after the acute 
CYP3A4 inhibitory phase has passed. After restarting the concomitant medication, subjects 
should be followed for loss of efficacy and a potential need for increasing dose of the 
concomitant medication. 
 
Management of mifepristone withdrawal after 7-day mifepristone administration 
Because CYP3A4 induction will decrease exponentially over a period of several weeks after 
stopping mifepristone, any change in dose of a concomitant medication during mifepristone 
therapy will need to be re-evaluated. Caution should be used when introducing new drugs in 
the first weeks after discontinuing mifepristone due to residual effects of CYP3A4 induction. 
 
CYP3A4 inducer medications 
Medications that are strong inducers of CYP3A4 such as carbamazepine, oxcarbazepine, 
phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John's Wort may 
decrease plasma mifepristone levels. Somewhat higher mifepristone doses may be required 
in subjects taking these concomitant medications. Mifepristone should not be used in doses 
higher than those defined in the protocol. 
 
CYP3A4 inhibitor medications 
Strong CYP3A4 inhibitor medications are expected to cause the largest increases in plasma 
mifepristone concentrations. The following strong CYP3A4 inhibitor medications are not 
allowed during the study: 
• ketoconazole, itraconazole, voriconazole, posaconazole 
• nefazodone 
• ritonavir, nelfinavir, indinavir, atazanavir, amprenavir, fosamprenavir, boceprevir 
• saquinavir, telaprevir 
• clarithromycin, telithromycin 
• conivaptan 
 
Contraindicated medications must be discontinued and cleared from a patients system prior to 
baseline (Study Day 0). The timing of medication discontinuation is based on the specific 
half-life of the parent compound and its active metabolites. Hence, contraindicated 
medications must be discontinued 7 days or 5 half-lives, whichever is greater, prior to 
baseline (Study Day 0). 
 
CYP2C9/2C8 substrate medications 
Mifepristone may increase the plasma drug concentration of concomitant medications with 
metabolism mediated by CYP2C9/2C8. Drugs with the largest increases will be those whose 
metabolism are largely or solely mediated by CYP2C9/2C8 and include: 
• Non-steroidal Anti-inflammatory drugs (NSAIDs) 
• Warfarin 

 
NSAIDs should be used at lower doses. For patients receiving warfarin, lower doses should be 
used during introduction of mifepristone; the prothrombin time should be carefully monitored to 
avoid over anticoagulation. The prothrombin time should be measured after the first dose of 
mifepristone and frequently thereafter. Prolongation of prothrombin time may not appear for a 
week or longer after mifepristone treatment begins. Any change in dose of a concomitant 
medication during mifepristone therapy will need to be re-evaluated after cessation of 
mifepristone. 
P-glycoprotein substrates 
Effects of mifepristone on p-glycoprotein are expected to be modest due to both inhibition and 
delayed induction. Effects of potential clinical significance are expected only for drugs with a 
narrow therapeutic margin of which digoxin is the main concern. Lower doses of digoxin 
should be considered when starting mifepristone. Adjustments to digoxin should be made 
during mifepristone and should be guided by blood digoxin levels. 
 
Corticosteroids 
All systemic corticosteroids are prohibited. Mifepristone is contraindicated in patients who 
require concomitant treatment with systemic corticosteroids for serious medical conditions or 
illnesses (e.g., immunosuppression after organ transplantation) because mifepristone 
antagonizes the effect of glucocorticoids. 
• Adrenostatic medications 
• Adrenostatic medications including metyrapone, ketoconazole, fluconazole, 
aminoglutethimide, etomidate are prohibited. 
• Neuromodulator drugs 
• Neuromodulator drugs that act at the hypothalamic-pituitary level, such as serotonin 
antagonists (cyproheptadine, ketanserin, retanserin) dopamine agonists 
(bromocriptine, cabergoline), GABA agonists (sodium valproate), and somatostatin 
receptor ligands (octreotide) are prohibited.