A Phase II Study of GDC-0032 (Taselisib) for Previously Treated PI3K Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung-MAP Sub-Study)
Phase: PHASE2
Conditions: Recurrent Squamous Cell Lung Carcinoma, Stage IV Squamous Cell Lung Carcinoma
Sponsor: SWOG Cancer Research Network

Cover Page for Clinical Trials Document posting 
 
 
Official Title:  
S1400B, “A PHASE II STUDY OF GDC-0032 (TASELISIB) FOR PREVIOUSLY TREATED 
PI3K POSITIVE PATIENTS WITH STAGE IV SQUAMOUS CELL LUNG CANCER (LUNG-
MAP SUB-STUDY)” 
 
 
NCT Number: 02785913 
 
 
Version Date: 
9/1/2017 
 
Description: 
S1400 [NCT 02154490] is the parent study to S1400B [NCT 02785913].  
The S1400 Lung-MAP study is considered one study under one IND consisting of: 
• 
S1400 Version Control Protocol  
• 
S1400 Main Screening Protocol Component 
• 
Multiple Sub-Studies (or sub-protocols) Components  
Each component is contained in its own separate document.   
S1400B is one of these components.  Each “component” consists of the protocol 
document and its associated informed consent document(s).  Since each screening 
and sub-study component operates independently from the other components contained 
in Lung-MAP, each has its own version date and NCT number. This is due to the complexity 
of the study and how it must be entered into different computer programs.  
 

S1400B: PI3K – GDC-0032  
 
 
TITLE  
A BIOMARKER-DRIVEN MASTER PROTOCOL FOR PREVIOUSLY TREATED  
SQUAMOUS CELL LUNG CANCER 
 
A PHASE II STUDY OF GDC-0032 (TASELISIB) FOR PREVIOUSLY TREATED  
PI3K POSITIVE PATIENTS WITH STAGE IV SQUAMOUS CELL LUNG CANCER 
(LUNG-MAP SUB-STUDY) 
 
 
NCT #02154490 
 
 
SUB-STUDY CHAIRS: 
STUDY AGENTS: 
 
 
Corey J. Langer, M.D. (Medical Oncology) 
Available from Pharmaceutical Collaborators: 
NCTN Group: NRG  
GDC-0032 (Taselisib) (NSC 778795)  
University of Pennsylvania, Hematology/ 
 
(IND-119672) 
  Oncology Division  
 
Abramson Cancer Center  
Available from Commercial Sources: 
3400 Spruce Street  
Docetaxel * (Taxotere®) (RP56976)  
12 Penn Tower  
 
(NSC 628503) 
Pennsylvania, PA 19104 
 
FAX: 215/615-5122 
 
E-mail: Corey.Langer@uphs.upenn.edu  
BIOSTATISTICIANS: 
 
 
James L. Wade III, M.D. 
Mary Redman, Ph.D. 
(Medical Oncology) 
Shannon McDonough, M.S. 
NCTN Group: SWOG  
Jieling Miao, M.S. 
Cancer Care Specialists of Central Illinois 
James Moon, M.S. 
210 W McKinley Ave  
SWOG Statistical Center 
Decatur, IL 62526 
1100 Fairview Ave N, M3-C102 
Phone: 217/876-6600 
P.O. Box 19024 
E-mail: jlwade3@sbcglobal.net 
Seattle, WA 98109-1024 
 
Phone: 206/667-4623 
 
FAX: 206/667-4408 
 
E-mail: mredman@fredhutch.org 
 
E-mail: smcdonou@fredhutch.org  
 
 
E-mail: jmiao@fredhutch.org 
 
 
E-mail: jmoon@fredhutch.org 
 
 
 
 
 
 
 
 
 
 
 
* Docetaxel is not a current study agent effective 12/18/2015. 

TABLE OF CONTENTS 
TITLE  ......................................................................................................................................................... 1 
TABLE OF CONTENTS ............................................................................................................................... 2 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION ....................... 4 
SCHEMA ....................................................................................................................................................... 5 
NEW SCHEMA ............................................................................................................................................. 5 
1.0 
OBJECTIVES .................................................................................................................................. 6 
1.1 
Primary Objectives ........................................................................................................................... 6 
1.2 
Secondary Objectives ...................................................................................................................... 6 
1.3 
Translational Medicine Objectives ................................................................................................... 6 
2.0 
BACKGROUND ............................................................................................................................... 7 
 
The Phosphoinositide 3-Kinase Pathway ........................................................................................ 7 
 
GDC-0032 (Taselisib) Clinical Data ................................................................................................. 7 
 
Rationale for GDC-0032 (Taselisib) - Dose Selection for S1400B .................................................. 8 
3.0 
DRUG INFORMATION .................................................................................................................... 8 
3.1 
Taselisib (GDC-0032) (NSC 778795) (IND-119672) ....................................................................... 9 
4.0 
STAGING CRITERIA ..................................................................................................................... 13 
5.0 
ELIGIBILITY CRITERIA ................................................................................................................ 13 
5.1 
Disease Related Criteria ................................................................................................................ 13 
5.2 
Clinical Laboratory Criteria ............................................................................................................. 14 
5.3 
Common Eligibility Criteria for all Sub-Studies .............................................................................. 14 
5.4 
Step 2 GDC-0032 Re-Registration ................................................................................................ 17 
6.0 
STRATIFICATION FACTORS ....................................................................................................... 19 
6.1 
Patients were randomized between GDC-0032 and docetaxel using block randomization. ......... 20 
6.2 
Randomization will be stratified by: ................................................................................................ 20 
7.0 
TREATMENT PLAN ...................................................................................................................... 20 
7.1 
Pre-Medication and Supportive Care ............................................................................................. 20 
7.2 
Treatment – S1400B ...................................................................................................................... 20 
7.3 
Drug Compliance Documentation .................................................................................................. 21 
7.4 
Concomitant Medications to Avoid ................................................................................................. 21 
7.5 
Criteria for Removal from Protocol Treatment ............................................................................... 22 
7.6 
Discontinuation of Treatment ......................................................................................................... 22 
7.7 
Follow-Up Period ............................................................................................................................ 22 
8.0 
TOXICITIES TO BE MONITORED AND DOSE MODIFICATIONS .............................................. 22 
8.1 
NCI Common Terminology Criteria for Adverse Events ................................................................ 22 
8.2  
General Considerations ................................................................................................................. 23 
8.3 
Dose Modifications GDC-0032 (Taselisib) ..................................................................................... 23 
8.4 
Dose Modifications – Docetaxel (Closed to accrual per Revision #3) ........................................... 31 
8.5 
Dose Modification Contacts ........................................................................................................... 34 
8.6 
Adverse Event Reporting ............................................................................................................... 34 
9.0 
STUDY CALENDAR ...................................................................................................................... 35 
9.1  
Arm 1 GDC-0032 (Taselisib) .......................................................................................................... 35 
9.2 
Arm 2 Docetaxel ............................................................................................................................. 37 
9.3  
Arm 3 Re-Registration – GDC-0032 (Taselisib) ............................................................................ 39 
10.0 
CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS ..................................................... 41 
11.0 
STATISTICAL CONSIDERATIONS .............................................................................................. 41 
11.1 
Primary Objective and Biomarker Prevalence ............................................................................... 41 
11.2 
Sample Size with Power Justification ............................................................................................ 42 
12.0 
DISCIPLINE REVIEW .................................................................................................................... 42 
13.0 
REGISTRATION GUIDELINES ..................................................................................................... 42 
13.1 
Registration Timing ........................................................................................................................ 42 
14.0 
DATA SUBMISSION SCHEDULE ................................................................................................ 42 
14.1 
Data Submission Requirements .................................................................................................... 42 
14.2 
Master Forms ................................................................................................................................. 42 
14.3 
Data Submission Procedures ........................................................................................................ 42 
14.4 
Data Submission Overview and Timepoints .................................................................................. 43 
15.0 
SPECIAL INSTRUCTIONS............................................................................................................ 45 
15.1 
SWOG Specimen Tracking System (STS) .................................................................................... 45 

15.2  
Correlative Studies and Banking  (Optional for Patients) .............................................................. 45 
15.3 
Radiology Review (Required) ........................................................................................................ 47 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS ................................................................... 48 
16.1 
Adverse Event Reporting Requirements........................................................................................ 48 
17.0 
BIBLIOGRAPHY ............................................................................................................................ 54 
 
 
 
 

CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
To submit site 
registration 
documents: 
For patient 
enrollments: 
 
Submit study data directly to the 
Lead 
Cooperative Group unless 
otherwise 
specified in the protocol: 
 
CTSU Regulatory Office 
1818 Market Street, 
Suite 1100 
Philadelphia, PA19103 
 
Fax: 215-569-0206 
 
Email:  
 
CTSURegulatory@ctsu.coc
cg.org 
 
For more information, call 
the CTSU Help Desk at 
888-823-5923 or the 
Regulatory Help Desk at 
866-651-CTSU. 
 
Please refer to the patient 
enrollment section of the 
protocol for instructions on 
using the Oncology Patient 
Enrollment Network (OPEN) 
which can be accessed at 
https://www.ctsu.org/OPEN_SY
STEM/ or 
https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk 
with any OPEN-related 
questions at 
ctsucontact@westat.com. 
 
 
 
Data collection for this study will be 
done exclusively through Medidata 
Rave.  Please see the data 
submission section of the protocol for 
further instructions.  
 
Other Tools and Reports: 
Institutions participating through the 
CTSU continue to have access to 
other tools and reports available to 
the SWOG Workbench.  Access this 
by using your active CTEP-IAM 
USER ID and password at the 
following url: 
https://crawb.crab.org/TXWB/ctsulog
on.aspx. 
The most current version of the study protocol and all supporting documents must be downloaded 
from the protocol-specific Web page of the CTSU Member Web site located at 
https://www.ctsu.org.  Access to the CTSU members’ website is managed through the Cancer Therapy 
and Evaluation Program - Identity and Access Management (CTEP-IAM) registration system and 
requires user log on with CTEP-IAM username and password. Permission to view and download this 
protocol and its supporting documents is restricted and is based on person and site roster assignment 
housed in the CTSU RSS. 
 
CTSU sites should follow procedures outlined in the protocol for site registration, Patient Enrollment 
Adverse Event Reporting, Data Submission (including ancillary studies), and Drug Procurement.  
For patient eligibility questions contact the SWOG Data Operations Center by phone or email: 
 
206-652-2267 
S1400question@crab.org 
 
For treatment or toxicity related questions contact S1400BMedicalquery@swog.org. 
For questions unrelated to patient eligibility, treatment, or data submission contact the CTSU 
Help 
Desk by phone or e-mail: 
 
CTSU General Information Line: 
888-823-5923 
ctsucontact@westat.com 
 
All calls and correspondence will be triaged to the appropriate CTSU representative. 
The CTSU Web site is located at https://www.ctsu.org 
 

SCHEMA 
OLD SCHEMA 
 
Patients registered prior to Revision #3 
 
Screening/Pre-Screening Registration 
 
 
Common Broad Platform CLIA Biomarker Profiling * 
 
 
PI3K Positive by FMI** 
 
 
S1400B 
 
 
Arm 1 
Arm 2 
Progression 
GDC-0032 Ø     Docetaxel 
 
Re-Registration Arm 3 *** 
GDC-0032 Ø 
 
* 
Archival formalin-fixed paraffin-embedded (FFPE) tumor, fresh core needle biopsy if needed 
** Notification of sub-study assignment will be provided by the SWOG statistical center (see Section 11.0 in S1400 for 
details).  
*** Optional re-registration to Arm 3- GDC-0032, (patients must have progressed as defined in Section 10.2d of S1400). 
Ø  Upon progression (as defined in Section 10.2d in S1400), patients may be eligible for another sub-study. The new 
sub-study assignment will be determined by the SWOG Statistical Center (see Section 14.4). 
 
NEW SCHEMA 
 
Patients registered after Revision #3 
 
Screening/Pre-Screening Registration 
 
 
Common Broad Platform CLIA Biomarker Profiling * 
 
 
PI3K Positive by FMI** 
 
 
S1400B *** 
    
 
 
 
Arm 1 
GDC-0032  
Progression Ø 
 
* 
Archival formalin-fixed paraffin-embedded (FFPE) tumor, fresh core needle biopsy if needed 
** 
Notification of sub-study assignment will be provided by the SWOG statistical center (see Section 11.0 in S1400 
for details). 
*** Arm 2 Docetaxel has been removed from the main schema as it is closed to accrual per Revision #3, Version Date 
11/18/15. 
Ø  Upon progression (as defined in Section 10.2d in S1400), patients may be eligible for another sub-study. The new 
sub-study assignment will be determined by the SWOG Statistical Center (see Section 14.4).  

 
1.0 
OBJECTIVES 
 
 
Included here are the objectives related to the single arm Phase II portion of Design #2 
(Sequential Phase II to Phase III) as described in S1400  
 
The objective of S1400B is to evaluate GDC-0032 (Taselisib), a phosphoinositide 3-kinase 
(PI3K) inhibitor, in PI3K-positive patients.  S1400B will utilize a broad definition of PI3K-
positivity for eligibility (Foundation Medicine [FMI] criteria as defined in Section 5.0 and 
11.1). However, the primary analyses will be performed first using a more restricted 
definition of PI3K-positivity (Genentech [GNE] criteria as defined in Section 11.1 of 
S1400B), followed by an evaluation using the more broad FMI criteria if the first analysis 
meets the pre-specified efficacy endpoints. 
 
1.1 
Primary Objectives 
 
a. 
Phase II Component 
 
The primary objective within the Phase II component of S1400B is to 
evaluate if there is sufficient evidence to continue to the Phase III 
component by evaluating the objective response rate (ORR) for PI3K 
GNE-positive patients registered to S1400B treated with GDC-0032. 
 
b. 
Phase III Component 
 
If the study meets the criteria specified in S1400 Section 11.2a, the study 
will be amended to include a follow-on randomized Phase III trial. 
 
1.2 
Secondary Objectives 
 
a. 
Phase II Component 
 
1. 
To evaluate investigator-assessed progression free survival (IA-
PFS) and overall survival (OS) in both the subset of patients 
defined to be PI3K GNE-positive and in the entire S1400B (PI3K 
FMI positive) study population treated with GDC-0032 
 
2. 
To evaluate ORR in the entire S1400B (PI3K FMI positive) study 
population treated with GDC-0032 to evaluate the Duration of 
Response (DoR) both in GNE positive and FMI positive. 
 
3. 
To evaluate the duration of response (DoR) both in the entire 
S1400B PI3K FMI positive study population and in GNE positive 
patients treated with GDC-0032 who achieve a CR or PR 
(confirmed and unconfirmed) by RECIST 1.1. 
 
4. 
To evaluate the frequency and severity of toxicities associated 
with GDC-0032 
 
1.3 
Translational Medicine Objectives 
 
a. 
To identify additional predictive tumor/blood biomarkers that may modify 
response or define resistance to the GDC-0032 beyond the chosen 
biomarker for biomarker-driven sub-studies. 
 
b. 
To identify potential resistance biomarkers at disease progression. 
 
c. 
To establish a tissue/ blood repository from patients with refractory 
squamous cell carcinoma (SCCA) of the lung. 

 
2.0 
BACKGROUND 
 
The Phosphoinositide 3-Kinase Pathway 
 
Phosphoinositide 3-kinase (PI3K) is a lipid kinase involved in tumor cell proliferation, 
survival, and migration upon activation by growth factor receptors and integrins.  PI3K 
catalyzes the phosphorylation of phosphatidylinositol-4,5-bisphosphate (PIP2) to generate 
phosphatidylinositol-3,4,5-trisphosphate (PIP3), a second messenger involved in the 
phosphorylation of AKT and associated proteins in the AKT-mTOR pathway.  (1, 2)  
Activating and transforming mutations, as well as amplification, in the p110α subunit of 
PI3K are commonly found in solid and hematological tumors.  In addition, the PI3K-AKT 
pathway is activated in numerous types of cancer by receptor tyrosine kinase signaling, 
the loss of the phosphatase tensin homolog (PTEN), or RAS mutations.  (3, 4, 5, 6) 
 
GDC-0032 (Taselisib) is a potent, selective small molecule inhibitor of Class 1 PI3K that is 
being developed by Genentech, Inc. as an anti-cancer therapeutic agent.  PI3K-AKT 
pathway activation has been implicated in several types of cancer.  (7, 8, 9) Activating and 
transforming mutations in the p110α subunit of PI3K are commonly found in tumors.  (10, 
11, 12)  The beta isoform of PI3K is involved in glucose metabolism as evidenced by 
increased glucose levels in conditional p110β knockout mice compared with wild-type mice 
following a glucose challenge test.  (13)  GDC-0032 (GDC-0032) has approximately 30-fold 
biochemical selectivity of the alpha isoform relative to the beta isoform and has been shown 
to be a potent inhibitor of growth in nonclinical models of PI3K-mutant tumors. 
 
GDC-0032 (Taselisib) Clinical Data 
 
The currently ongoing and planned studies are described below.   
 
Study PMT4979g 
 
Study PMT4979g is an open-label, Phase I/II study evaluating the safety and tolerability of 
GDC-0032 in patients with locally advanced or metastatic solid tumors.  Patients have been 
enrolled in three parts: a dose-escalation part (Stage 1) and an expansion part (Stage 2) 
and a Phase 2 part. The dose-escalation stage evaluated the safety and pharmacokinetics 
of increasing doses of single-agent GDC-0032 administered QD in a 28-day cycle.  Stage 
2 includes expansion cohorts with single-agent GDC-0032 and in combination with either 
letrozole or fulvestrant in a Ph1b setting for breast cancer patients.  The Phase 2 portion 
consists of GDC-0032 and fulvestrant in a less heavily pretreated breast cancer patient 
population. 
 
As of 10-31-13, single-agent GDC-0032 dose escalation had been completed with 
34 patients enrolled at doses with a range of 3-16 mg.  GDC-0032 was well tolerated in the 
first three cohorts (3, 5, and 8 mg), with no patients experiencing a dose limiting toxicity 
(DLT).  At the 16-mg dose level, 2 of the 11 safety evaluable patients experienced a DLT 
(Grade 4 hyperglycemia and Grade 3 fatigue).  At the 12-mg dose level, 1 of the 10 safety 
evaluable patients experienced a DLT of Grade 3 acute renal failure.  Although the single 
agent GDC-0032 maximum tolerated dose (MTD) was not exceeded at the 16-mg dose 
level, the recommended GDC-0032 dose and schedule for the single agent expansion 
cohorts was 9 mg daily on the basis of long-term safety data through multiple treatment 
cycles.   
 
Confirmed partial responses have been observed in dose escalation in patients with 
PIK3CA mutant tumors only.  This includes a confirmed partial response observed in a 
PIK3CA-mutant NSCLC patient treated at the 3 mg QD dose level.  Other partial responses 
have been observed in PIK3CA-mutant breast cancer patients at the 5-12mg QD dose 
levels.  

 
Clinical pharmacodynamic data with single-agent GDC-0032 suggests promising 
pharmacodynamic knockdown of the PI3K signaling pathway beginning at 3 mg 
QD.  Pharmacodynamic knockdown of the PI3K pathway based upon reverse phase 
protein array analysis of paired tumor biopsies (pre-treatment and during GDC-0032 
treatment) has been observed in at the lowest dose tested of single agent 3 mg QD in a 
NSCLC patient.  Decreases in mean SUV uptake via FDG-PET analysis that correlate with 
inhibited glucose uptake are another pharmacodynamics marker of PI3K pathway 
inhibition.  Such decreases have also been observed beginning at the lowest dose tested 
of 3 mg QD with single-agent GDC-0032  
 
64 patients have been enrolled in the single-agent expansion cohorts at 9mg QD.  The 
adverse events observed at the 9 mg QD dose level are expected toxicities that have been 
observed with GDC-0032 at higher dose levels.   
 
Dose escalation of GDC-0032 in combination with either fulvestrant or letrozole has been 
completed.  No dose limiting toxicities were observed at either the 6 mg or 9 mg dose levels 
of GDC-0032 when combined with either letrozole (n = 28) or fulvestrant (n = 27).  The 
6mg dose level was chosen for the Phase II portion of the study (GDC-0032 with 
fulvestrant), and enrollment is ongoing (n = 22).   
 
Study GO27802 
 
Study GO27802 is a Phase Ib study that is examining the safety, tolerability of GDC-0032 
in combination with either paclitaxel or docetaxel in patients with advanced HER2-negative 
breast cancer.  Dose escalation has begun recently with 8 patients treated.   
 
Rationale for GDC-0032 (Taselisib) - Dose Selection for S1400B  
 
GDC-0032 4 mg PO QD in the 2 mg tablet formulation has been selected as the dosing 
regimen for this 2 mg sub-study based on both safety and efficacy considerations with the 
goal of maximizing drug exposure while maintaining long-term tolerability.  This dose is 
equivalent to 6 mg PO QD in the capsule formulation. First, pharmacodynamic knockdown 
of the PI3K pathway has been observed beginning at the 3 mg cohort in the capsule 
formulation in NSCLC patients by tumor biopsies and FDG-PET.  This dose is equivalent 
to 2 mg in the tablet formulation. Second, anti-tumor activity has been observed in patients 
with PIK3CA-mutant tumors, with a confirmed partial response in a PIK3CA-mutant NSCLC 
patient at the 3 mg dose level in the capsule formulation and a confirmed partial response 
in a PIK3CA-mutant breast cancer patient at the 5 mg dose level with the capsule 
formulation.  These doses are equivalent to 2 mg and 3.3 mg in the tablet formulation, 
respectively.  Third, although the 9 mg PO QD dose in the capsule formulation (equivalent 
to 6 mg in the tablet formulation) has been tolerated in the single agent expansion cohorts, 
we believe that for this trial and this squamous NSCLC patient population with their various 
comorbidities, the 4 mg PO QD in the 2 mg tablet formulation (equivalent to 6 mg in the 
capsule formulation) offers an optimal balance between efficacy and safety considerations. 
 
3.0 
DRUG INFORMATION 
 
For information regarding Investigator’s Brochures, please refer to SWOG Policy 15. 
 
For this study, GDC-0032 is investigational and is being provided under an IND held by 
SWOG.  For INDs filed by SWOG, the protocol serves as the Investigator Brochure for the 
performance of the protocol.  In such instances submission of the protocol to the IRB should 
suffice for providing the IRB with information about the drug.  However, in cases where the 
IRB insists on having the official Investigator Brochure from the company, further 
information may be requested by contacting the SWOG Operations Office at 210/614-
8808. 

 
3.1 
Taselisib (GDC-0032) (NSC 778795) (IND-119672) 
 
a. 
PHARMACOLOGY 
 
Mechanism of Action: GDC-0032 is an inhibitor of Class I phosphoinositide 
3-kinase (PI3K) that belongs to a benzoxepin class and is being developed 
as an anti-cancer agent.  GDC-0032 is a potent, selective inhibitor of Class 
IPI3K alpha, delta and gamma p110- isoforms, with approximately 30-fold 
less inhibition of the p110-beta isoform.  Nonclinical studies with GDC-
0032 demonstrate that GDC-0032 treatment results in a substantial 
reduction of PI3K pathway markers, including phosphorylated Akt (pAkt), 
phosphorylated PRAS40 (pPRAS40), and phosphorylated S6 (pS6, also 
known as PS6RP).  As a result of robust PI3K pathway suppression, GDC-
0032 inhibits proliferation of human cancer cell lines, particularly breast 
cancer cell lines harboring p110α-mutations in vitro and in tumor xenograft 
models.  GDC-0032 has an in vitro and nonclinical in vivo absorption, 
distribution, metabolism, and elimination profile, characteristic of an orally 
administered compound that can achieve clinical exposure consistent with 
nonclinical efficacy findings described below.  The results of the nonclinical 
toxicology program for GDC-0032 support the evaluation of GDC-0032 as 
a potential therapeutic agent for cancer. 
 
b. 
PHARMACOKINETICS 
 
1. 
Absorption: 
GDC-0032 
was 
moderately-to-well 
absorbed 
following oral administration, with absolute bioavailability of 57% 
in humans. Median time to maximum concentration was 
approximately 3 hours. Administration of GDC-0032 with a high-
fat meal had minimal effect on exposure.  
 
2. 
Distribution: The plasma protein binding of GDC-0032 ranged 
from 70.7% to 97.6% bound in mouse, rat, rabbit, dog, monkey, 
and human.  Binding to 40 mg/mL human serum albumin ranged 
from 64.7% to 67.3% and appeared to be independent of the 
concentration of GDC-0032 tested.  Binding to 1 mg/mL of human 
alpha-1 acid glycoprotein ranged from 45.0% to 58.3% and was 
approximately 23% lower at 20 µM than at 0.5 µM GDC-0032. 
 
GDC-0032 had a moderate volume of distribution relative to total 
body water across all nonclinical species.  
 
3. 
Metabolism: No human-specific metabolites were observed in 
plasma from the comparison of metabolites from [14C] in vivo 
studies in rat and human. Oxidation and to a lesser extent 
hydrolysis appear to be the major metabolism pathways in rats. 
CYP3A4 is the primary CYP isoform responsible for the oxidative 
metabolism of GDC-0032. 
 
4. 
Elimination: The major route of excretion in rats and dogs was via 
the bile (approximately 20% and 69% of the dose in rats and dogs, 
respectively). Renal elimination was minor in both species, 
corresponding to less than 6% of the dose. Plasma half-life ranged 
from 37 to 44 hours. 
 
c. 
ADVERSE EFFECTS 
 

1. 
Adverse Events: The Comprehensive Adverse Events and 
Potential Risks list (CAEPR) provides a single list of reported 
and/or potential adverse events (AE) associated with an agent 
using a uniform presentation of events by body system.  Refer to 
the 
'CTEP, 
NCI 
Guidelines: 
Adverse 
Event 
Reporting 
Requirements' 
http://ctep.cancer.gov/protocolDevelopment/electronic_applicatio
ns/docs/aeguidelines.pdf for further clarification. Frequency is 
provided based on 425 patients. Below is the CAEPR for GDC-
0032. 
 
Version 2.1, January 24, 20161 
Adverse Events with Possible  
 Relationship to GDC-0032 
 (CTCAE 4.0 Term) 
[n= 425] 
Likely (>20%) 
Less Likely (<=20%) 
Rare but 
Serious (<3%) 
GASTROINTESTINAL DISORDERS 
 
Abdominal pain 
 
 
Colitis 
 
Diarrhea 
 
 
 
Dry mouth 
 
 
Dyspepsia 
 
 
Mucositis oral 
 
Nausea 
 
 
 
Vomiting 
 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
Fatigue 
 
 
INVESTIGATIONS 
 
Alanine aminotransferase 
increased 
 
 
Aspartate 
aminotransferase 
increased 
 
 
Neutrophil count 
decreased 
 
METABOLISM AND NUTRITION DISORDERS 
Anorexia 
 
 
Hyperglycemia 
 
 
NERVOUS SYSTEM DISORDERS 
 
Dysgeusia 
 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
 
 
Pneumonitis 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
 
Dry skin 
 
 
Pruritus 
 
 
Skin and subcutaneous 
tissue disorders (rash)2 
 
 
1 This table will be updated as the toxicity profile of the agent is 
revised. Updates will be distributed to all Principal Investigators 
at the time of revision. The current version can be obtained by 
contacting PIO@CTEP.NCI.NIH.GOV.  Your name, the name of 
the investigator, the protocol and the agent should be included 
in the e-mail. 

2 Rash may include Rash, Rash maculo-papular, Rash 
erythematous, Rash follicular, Rash generalized, Dermatitis 
exfoliative, Rash macular, Rash maculovesicular, Rash popular, 
Rash pustular, Rash pruritus, Rash morbilliform, Rash 
papulosquamous, and Rash vesicular.  
 
Adverse events reported on GDC-0032 trials, but for which 
there is insufficient evidence to suggest that there was a 
reasonable possibility that GDC-0032 caused the adverse 
event: 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Anemia 
GASTROINTESTINAL DISORDERS - Constipation; Oral pain 
INFECTIONS AND INFESTATIONS - Sepsis 
INVESTIGATIONS - Cholesterol high; Lymphocyte count de-
creased; White blood cell decreased 
MUSCULOSKELETAL 
AND 
CONNECTIVE 
TISSUE 
DISORDERS - Musculoskeletal and connective tissue disorder - 
Other (muscle spasms); Myalgia 
NERVOUS SYSTEM DISORDERS – Dizziness; Peripheral 
sensory neuropathy 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
– Respiratory failure 
 
Note: GDC-0032 (taselisib) in combination with other agents 
could cause an exacerbation of any adverse event currently 
known to be caused by the other agent, or the combination may 
result in events never previously associated with either agent. 
 
2. 
Pregnancy and Lactation: GDC-0032 is known to cross the 
placenta and may cause harm to the fetus or affect reproductive 
capacity when given to pregnant women. GDC-0032 should not 
be administered to pregnant women. Women of childbearing 
potential and male partners of women of childbearing potential 
should take necessary precautions to avoid pregnancy while 
receiving GDC-0032 during the protocol and for 30 days for 
women and 90 days for males following the last dose. It is not 
known whether GDC-0032 is excreted in human breast milk.  
GDC-0032 should not be administered to nursing mothers. 
 
3. 
Drug Interactions:  GDC-0032 is metabolized by CYP3A4 and 
metabolism may be affected by strong inhibitors and inducers of 
CYP3A4. GDC-0032 displays weak time-dependent inhibition of 
CYP3A4 and has the potential to induce CYP3A4/5. In vitro 
studies showed that GDC-0032 was a substrate of P-glycoprotein 
(P-gp) and breast cancer resistance protein (BCRP) but not a 
substrate of OATP1B1 and OATP1B3. GDC-0032 has the 
potential to inhibit the transport of substrates of OCT1 and OCT2. 
 
Due to potential drug interactions, a complete patient medication 
list, including GDC-0032, should be screened prior to initiation of 
and during treatment with GDC-0032. See S1400B Section 8.0 
Toxicities to be Monitored and Dosage Modifications. 
 
d. 
DOSING & ADMINISTRATION 
 
1. 
Dosing:  See S1400B Section 7.0, Treatment Plan. 
 

2. 
Administration Instructions:  GDC-0032 should be administered 
orally at the same time of day +/- 2 hours regardless of meals, 
unless otherwise instructed.  The GDC-0032 administration is 4 
mg (2 mg tablets x 2) PO daily. If patient vomits dose, dose should 
not be retaken. Avoid grapefruit or grapefruit juice. 
 
e. 
HOW SUPPLIED 
 
1. 
GDC-0032 will be supplied by Genentech, Inc., and distributed by 
the CTEP, DCTD, NCI. 
 
2. 
GDC-0032 will be supplied as 2 mg tablets as a white to off-white, 
film-coated tablet. Inert ingredients include:  lactose monohydrate, 
microcrystalline cellulose, croscarmellose sodium, magnesium 
stearate and Opadry 2. Each bottle contains 30 tablets. 
 
f. 
STORAGE, PREPARATION & STABILITY 
 
1. 
GDC-0032 tablets should be stored at room temperature not to 
exceed 25°C.   
 
2. 
Sites and subjects are advised to keep GDC-0032 in its original 
packaging. 
 
3. 
Stability studies demonstrate that temperature excursions of up to 
40oC for up to 6 months have no impact on product quality. 
 
g. 
DRUG ORDERING & ACCOUNTABILITY 
 
1. 
Drug Ordering: Study specific supplies will be provided to sites 
once a patient has been randomized.  Starter supplies will not be 
provided.  NCI-supplied agents may be requested by the Principal 
Investigator (or their authorized designee) at each participating 
institution.  Pharmaceutical Management Branch (PMB) policy 
requires that drug be shipped directly to the institution where the 
patient is to be treated. PMB does not permit the transfer of agents 
between institutions (unless prior approval from PMB is 
obtained).  The CTEP assigned protocol number (S1400B) must 
be used for ordering all CTEP supplied investigational 
agents.  The responsible investigator at each participating 
institution must be registered with CTEP, DCTD through an 
annual submission of FDA Form 1572 and a CV.  If there are 
several participating investigators at one institution, CTEP-
supplied investigational agents for the study should be ordered 
under the name of one lead investigator at that institution. Active 
CTEP-registered 
investigators 
and 
investigator-designated 
shipping designees and ordering designees can submit agent 
requests through the PMB Online Agent Order Processing 
(OAOP) 
application 
< 
https://eapps-
ctep.nci.nih.gov/OAOP/pages/login.jspx >.  Access to OAOP 
requires the establishment of a CTEP Identity and Access 
Management (IAM) account < https://eapps-ctep.nci.nih.gov/iam/ 
> and the maintenance of an “active” account status and a 
“current” password.   For questions about drug orders, transfers, 
returns, or accountability, call 240/276-6575 Monday through 
Friday between 8:30 am and 4:30 pm (ET) or email 
PMBAfterHours@mail.nih.gov anytime. 
 

2. 
Drug Handling and Accountability 
 
a. 
Drug Accountability: The investigator, or a responsible 
party designated by the investigator, must maintain a 
careful record of the receipt, disposition, and return of all 
drugs received from the PMB using the mandatory Oral 
NCI Drug Accountability Record Form DARF available on 
the NCI home page (http://ctep.cancer.gov). 
 
b. 
Electronic logs are allowed as long as a print version of 
the log process is the exact same appearance as the 
current NCI DARF. 
 
3. 
Drug Return and/or Disposition Instruction 
 
a. 
All undispensed drug supplies should be returned to the 
PMB. When it is necessary to return study drug (e.g., 
sealed bottles remaining when PMB sends a stock 
recovery letter), investigators should return the study drug 
to the PMB using the NCI Return Agent Form available on 
the NCI home page (http://ctep.cancer.gov). 
 
b. 
Drug expiration:  Stability testing is ongoing.  PMB will 
send a stock recovery letter when notified that the agent 
is no longer suitable for use. 
 
4. 
Contact Information  
 
Questions about drug orders, transfers, returns or accountability should 
be addressed to the PMB by calling 240/276-6575 Monday through Friday 
between 8:30 am and 4:30 pm Eastern Time. 
 
4.0 
STAGING CRITERIA 
See Section 4.0 of S1400 for staging criteria. 
 
5.0 
ELIGIBILITY CRITERIA 
Patient must meet the eligibility criteria in Section 5.0 of S1400B to be eligible for S1400B.  
If the patient does not meet the sub-study specific eligibility criteria listed in Section 5.1 and 
Section 5.2 of S1400B, but meets the common sub-study criteria listed in Section 5.3 of 
S1400B, submit the S1400 Request for Sub-Study Reassignment Form for sub-study 
reassignment. Patients on Arm2, docetaxel, that have progressed and are proceeding to 
Re-Registration must meet the eligibility criteria in Section 5.4 of S1400B to be eligible. 
Any potential eligibility issues should be addressed to the Data Operations Center in 
Seattle at S1400question@crab.org prior to registration. 
 
5.1 
Disease Related Criteria 
 
a. 
Patients must be assigned to S1400B.  S1400B biomarker eligibility 
defined as PI3K Positive is as follows: 
 
Gene 
Alteration 
type 
Eligible alteration 
PIK3CA 
Substitution 
R38C, R38H, E81K, R88Q, R93Q, 
R93W, P104L, P104R, G106V, G106R, 
P104_G106>R, R108H, E110del, E110K, 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.2 
Clinical Laboratory Criteria 
 
a. 
Patients must have a HbA1c < 7% and fasting glucose < 125 mg/dL 
obtained within 28 days prior to sub-study registration. 
 
b. 
Patients must not have Type I or II diabetes that requires anti-
hyperglycemic medication. 
 
c. 
Patients must not have active or a history of small or large intestine 
inflammation such as Crohn’s disease or ulcerative colitis. 
 
d. 
Patients must not require daily supplemental oxygen. 
 
e. 
Patients must be able to take oral medications.  Patients may not have 
any impairment of gastrointestinal function or gastrointestinal disease 
that may significantly alter the absorption of GDC-0032 (e.g. ulcerative 
disease, uncontrolled nausea, vomiting, diarrhea, malabsorption 
syndrome, or small bowel resection). 
 
f. 
Patients must not be taking, nor plan to take while on protocol treatment 
and for 14 days post the last dose of study treatment, drugs, herbal 
supplements or foods that are known to be strong/moderate CYP3A4 
substrates.  A list of these medications can be found in Section 7.4 of 
this sub-study. 
 
g. 
Patients must have a Lipase and Amylase performed within 7 days prior 
to sub-study registration. Additional timepoints are noted in Section 9.0, 
Study Calendar. 
 
h. 
Patients must also be offered participation in banking for future use of 
specimens as described in Section 15.0. 
5.3 
Common Eligibility Criteria for all Sub-Studies 
 
The S1400 Common Eligibility Criteria have been incorporated into Section 5.0 of 
each sub-study for ease of reference. 
K111E, K111N, K111del, G118D, 
V344G, V344M, N345K, N345I, E365K, 
C378F, E418K, C420R, E453K, E453Q, 
P539R, E542K, E542A, E542V, E542G, 
E542Q, E545A, E545G, E545K, E545Q, 
E545D, Q546E, Q546H, Q546K, Q546L, 
Q546P, Q546R, E726K, G1007R, 
D1017H, Y1021C, Y1021H, T1025A, 
A1035V, A1035T, M1043I, M1043L, 
M1043V, H1047L, H1047R, H1047Y, 
H1047N, H1047Q, G1049R, G1049S, 
I1058L 
Fusion 
None 
Amplification None 

 
a. 
Patients whose biomarker profiling results indicate the presence of an 
EGFR mutation or EML4/ALK fusion are not eligible. Due to existence of 
approved therapies the biomarker exclusion rules are as follows: 
 
Gene 
Alteration 
type 
Ineligible Alteration 
EGFR 
Substitution 
L858R, T790M, A289V, G719A, 
S768I, G719C, R108K, G598V, 
R222C, L62R, L861Q, P596L, 
V774M 
Indel 
non-frame shifting insertions or 
deletions between amino acids 
740 and 780, in exons 19 and 20, 
transcript NM_005228 
Fusion 
None 
Amplification 
None 
ALK 
Substitution 
None 
Indel 
None 
Fusion 
EML4-ALK, CLIP4-ALK, CLTC-ALK, 
KIF5B-ALK, NPM1-ALK, RANB2-ALK, 
STRN-ALK, TFG-ALK 
Amplification 
None 
 
b. 
Patients must have progressed (in the opinion of the treating physician) 
following the most recent line of therapy. 
 
c. 
Patients must not have received any prior systemic therapy (systemic 
chemotherapy, immunotherapy or investigational drug) within 21 days 
prior to sub-study registration. Patients must have recovered (≤ Grade 1) 
from any side effects of prior therapy.  Patients must not have received 
any radiation therapy within 14 days prior to sub-study registration. (See 
5.3e for criteria regarding therapy for CNS metastases). 
 
d. 
Patients must have measurable disease (see Section 10.1) documented 
by CT or MRI.  The CT from a combined PET/CT may be used to 
document only non-measurable disease unless it is of diagnostic quality 
as defined in Section 10.1c.  Measurable disease must be assessed within 
28 days prior to sub-study registration.  Pleural effusions, ascites and 
laboratory parameters are not acceptable as the only evidence of disease.  
Non-measurable disease must be assessed within 42 days prior to sub-
study registration.  All disease must be assessed and documented on the 
Baseline Tumor Assessment Form.  Patients whose only measurable 
disease is within a previous radiation therapy port must demonstrate 
clearly progressive disease (in the opinion of the treating investigator) prior 
to registration. See Sections 15.0 and 18.1c for guidelines and submission 
instructions for required central radiology review. 
 
e. 
Patients must have a CT or MRI scan of the brain to evaluate for CNS 
disease within 42 days prior to sub-study registration.  Patient must not 
have leptomeningeal disease, spinal cord compression or brain 
metastases unless:  (1) metastases have been locally treated and have 
remained clinically controlled and asymptomatic for at least 14 days 
following treatment and prior to registration, AND (2) patient has no 
residual neurological dysfunction and has been off corticosteroids for at 
least 24 hours prior to sub-study registration. 

 
f. 
Patient must have fully recovered from the effects of surgery at least 14 
days prior to sub-study registration. 
 
g. 
Patients must not be planning to receive any concurrent chemotherapy, 
immunotherapy, 
biologic 
or 
hormonal 
therapy 
for 
cancer 
treatment.  Concurrent use of hormones for non-cancer-related conditions 
(e.g., insulin for diabetes and hormone replacement therapy) is 
acceptable. 
 
h. 
Patients must have an ANC ≥ 1,500/mcl, platelet count ≥ 100,000 mcl, and 
hemoglobin ≥ 9 g/dL obtained within 28 days prior to sub-study 
registration. 
 
i. 
Patients must have adequate hepatic function as defined by serum 
bilirubin ≤ Institutional Upper Limit of Normal (IULN) and either ALT or AST 
≤ 2 x IULN within 28 days prior to sub-study registration (if both ALT and 
AST are done, both must be < 2 IULN).  For patients with liver metastases, 
bilirubin and either ALT or AST must be ≤ 5 x IULN (if both ALT and AST 
are done, both must be ≤ 5 x IULN). 
 
j. 
Patients must have a serum creatinine ≤ the IULN OR measured or 
calculated creatinine clearance ≥ 50 mL/min using the following Cockroft-
Gault Formula: 
 
Calculated Creatinine Clearance = (140 - age) X (actual body weight in kg) † 
 
 
72 x serum creatinine 
 
Multiply this number by 0.85 if the patient is a female. These tests must 
have been performed within 28 days prior to sub-study registration. 
†The kilogram weight is the patient weight with an upper limit of 140% of 
the IBW. 
*Actual lab serum creatinine value with a minimum of 0.8 mg/dL. 
 
k. 
Patients must have Zubrod performance status of 0-1 1 (see Section 10.4) 
documented within 28 days prior to sub-study registration. 
 
l. 
Patients must not have any Grade III/IV cardiac disease as defined by the 
New York Heart Association Criteria (i.e., patients with cardiac disease 
resulting in marked limitation of physical activity or resulting in inability to 
carry on any physical activity without discomfort), unstable angina 
pectoris, and myocardial infarction within 6 months, or serious 
uncontrolled cardiac arrhythmia (see Section 18.1b). 
 
m. 
Patients must not have documented evidence of acute hepatitis or have 
an active or uncontrolled infection. 
 
n. 
Patients with a known history of HIV seropositivity: 
 
1. 
Must have undetectable viral load using standard HIV assays in 
clinical practice. 
2. 
Must have CD4 count ≥ 400/mcL. 
3. 
Must not require prophylaxis for any opportunistic infections (i.e., 
fungal, mAC, or PCP prophylaxis). 
4. 
Must not be newly diagnosed within 12 months prior to sub-study 
registration.  

 
o. 
Prestudy history and physical exam must be obtained within 28 days prior 
to sub-study registration. 
 
p. 
No other prior malignancy is allowed except for the following:  adequately 
treated basal cell or squamous cell skin cancer, in situ cervical cancer, 
adequately treated Stage I or II cancer from which the patient is currently 
in complete remission, or any other cancer from which the patient has 
been disease free for five years. 
 
q. 
Patients must not be pregnant or nursing.  Women/men of reproductive 
potential must have agreed to use an effective contraceptive method.  A 
woman is considered to be of "reproductive potential" if she has had 
menses at any time in the preceding 12 consecutive months.  In addition 
to routine contraceptive methods, "effective contraception" also includes 
heterosexual celibacy and surgery intended to prevent pregnancy (or with 
a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral 
oophorectomy or bilateral tubal ligation.  However, if at any point a 
previously celibate patient chooses to become heterosexually active 
during the time period for use of contraceptive measures outlined in the 
protocol, he/she is responsible for beginning contraceptive measures. 
 
r. 
As a part of the OPEN registration process (see Section 13.4 for OPEN 
access instructions) the treating institution's identity is provided in order to 
ensure that the current (within 365 days) date of institutional review board 
approval for this study has been entered in the system. 
 
s. 
Patients with impaired decision-making capacity are eligible as long as 
their neurological or psychological condition does not preclude their safe 
participation in the study (e.g., tracking pill consumption and reporting 
adverse events to the investigator). 
 
t. 
Patients must be informed of the investigational nature of this study and 
must sign and give written informed consent in accordance with 
institutional and federal guidelines. 
 
5.4 
Step 2 GDC-0032 Re-Registration 
 
a. 
Patients must have progressed (as defined in Section 10.2d in S1400) on 
Arm 2 (docetaxel) of this sub-study. 
 
b. 
Patients must not have received any prior systemic therapy (systemic 
chemotherapy, immunotherapy or investigational drug) within within 21 
days prior to Step 2 re-registration. Patients must have recovered (< Grade 
1) from any side effects of prior therapy. 
 
c. 
Patients must have measurable disease (see Section 10.1) documented 
by CT or MRI.  The CT from a combined PET/CT may be used to 
document only non-measurable disease unless it is of diagnostic quality 
as defined in Section 10.1c.  Measurable disease must be assessed within 
28 days prior to Step 2 re-registration.  Pleural effusions, ascites and 
laboratory parameters are not acceptable as the only evidence of disease.  
Non-measurable disease must be assessed within 42 days prior to Step 2 
re-registration.  All disease must be assessed and documented on the 
Baseline Tumor Assessment Form.  Patients whose only measurable 
disease is within a previous radiation therapy port must demonstrate 
clearly progressive disease (in the opinion of the treating investigator) prior 

to registration. See Sections 15.0 and 18.1c for guidelines and submission 
instructions for required central radiology review. 
 
d. 
Patients must have a CT or MRI scan of the brain to evaluate for CNS 
disease within 42 days prior to Step 2 Re-Registration.  Patient must not 
have leptomeningeal disease, spinal cord compression or brain 
metastases unless: (1) metastases have been locally treated and have 
remained clinically controlled and asymptomatic for at least 14 days 
following treatment and prior to re-registration, AND (2) patient has no 
residual neurological dysfunction and has been off corticosteroids for at 
least 24 hours prior to re-registration. 
 
e. 
Patients must not be planning to receive any concurrent chemotherapy, 
immunotherapy, biologic or hormonal therapy for cancer treatment.  
Concurrent use of hormones for non-cancer-related conditions (e.g., 
insulin for diabetes and hormone replacement therapy) is acceptable. 
 
f. 
Patients must have an ANC ≥ 1,500/mcl, platelet count ≥ 100,000 mcl, and 
hemoglobin ≥ 9 g/dL obtained within 28 days prior to Step 2 Re-
Registration. 
 
g. 
Patients must have adequate hepatic function as defined by serum 
bilirubin ≤ Institutional Upper Limit of Normal (IULN) and either ALT or AST 
≤ 2 x IULN within 28 days prior to Step 2 Re-Registration (if both ALT and 
AST are done, both must be < 2 IULN).  For patients with liver metastases, 
bilirubin and either ALT or AST must be ≤ 5 x IULN (if both ALT and AST 
are done, both must be ≤ 5 x IULN). 
 
h. 
Patients must have a HbA1c < 7% and fasting glucose < 125 mg/dL 
obtained within 28 days prior to Step 2 Re-Registration. 
 
i. 
Patients must have a serum creatinine ≤ the IULN OR measured or 
calculated creatinine clearance ≥ 50 mL/min using the following Cockroft-
Gault Formula: 
 
Calculated Creatinine Clearance = (140 - age) X (actual body weight in kg) † 
 
72 x serum creatinine* 
 
Multiply this number by 0.85 if the patient is a female. These tests must 
have been performed within 28 days prior to Step 2 Re-Registration. 
 
† The kilogram weight is the patient weight with an upper limit of 140% of 
the IBW. 
• Actual lab serum creatinine value with a minimum of 0.8 mg/dL. 
 
j. 
Patients must have a Lipase and Amylase performed within 7 days prior 
to sub-study registration. Additional timepoints are noted in Section 9.0, 
Study Calendar. 
 
k. 
Patients must have Zubrod performance status of 0-1   (see Section 10.4) 
documented within 28 days prior to Step 2 Re-Registration. 
 
l. 
Patients must not have any Grade III/IV cardiac disease as defined by the 
New York Heart Association Criteria (i.e., patients with cardiac disease 
resulting in marked limitation of physical activity or resulting in inability to 
carry on any physical activity without discomfort), unstable angina 
pectoris, and myocardial infarction within 6 months, or serious 
uncontrolled cardiac arrhythmia (see Section 18.1b). 

 
 
m. 
Patients must not have documented evidence of acute hepatitis or have 
an active or uncontrolled infection. 
 
n. 
Patients with a known history of HIV seropositivity: 
 
1. 
Must have undetectable viral load using standard HIV assays in 
clinical practice. 
2. 
Must have CD4 count ≥ 400/mcL. 
3. 
Must not require prophylaxis for any opportunistic infections (i.e., 
fungal, mAC, or PCP prophylaxis). 
4. 
Must not be newly diagnosed within 12 months prior to re-
registration.  
 
o. 
Prestudy history and physical exam must be obtained within 28 days prior 
to re-registration. 
 
p. 
No other prior malignancy is allowed except for the following:  adequately 
treated basal cell or squamous cell skin cancer, in situ cervical cancer, 
adequately treated Stage I or II cancer from which the patient is currently 
in complete remission, or any other cancer from which the patient has 
been disease free for five years. 
 
q. 
Patients must not be pregnant or nursing.  Women/men of reproductive 
potential must have agreed to use an effective contraceptive method.  A 
woman is considered to be of "reproductive potential" if she has had 
menses at any time in the preceding 12 consecutive months.  In addition 
to routine contraceptive methods, "effective contraception" also includes 
heterosexual celibacy and surgery intended to prevent pregnancy (or with 
a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral 
oophorectomy or bilateral tubal ligation.  However, if at any point a 
previously celibate patient chooses to become heterosexually active 
during the time period for use of contraceptive measures outlined in the 
protocol, he/she is responsible for beginning contraceptive measures. 
 
r. 
As a part of the OPEN registration process (see Section 13.4 for OPEN 
access instructions) the treating institution's identity is provided in order to 
ensure that the current (within 365 days) date of institutional review board 
approval for this study has been entered in the system. 
 
s. 
Patients with impaired decision-making capacity are eligible as long as 
their neurological or psychological condition does not preclude their safe 
participation in the study (e.g., tracking pill consumption and reporting 
adverse events to the investigator). 
 
t. 
Patients must be informed of the investigational nature of this study and 
must sign and give written informed consent in accordance with 
institutional and federal guidelines. 
 
6.0 
STRATIFICATION FACTORS 
 
Prior to Revision #3, (Version Date 11/18/15) patients were stratified as follows below.  As 
the Phase II trial has been modified to a single arm study design, the following 
randomization and stratification applied to the randomized Phase II/III are no longer 
required. However, patients will continue to be stratified by PIK3CA mutation status per 
Genentech (GNE) criteria (positive vs negative as defined in Section 11.1). 
 

6.1 
Patients were randomized between GDC-0032 and docetaxel using block 
randomization. 
 
6.2 
Randomization will be stratified by: 
 
a. 
Zubrod Performance Status (0- vs. 2) 
 
b. 
Gender (male vs. female) 
 
c. 
Number of prior therapies (1 vs. 2 or more) 
 
d. 
PIK3CA mutation status per Genentech (GNE) criteria (positive vs 
negative as defined in Section 11.1).  
 
7.0 
TREATMENT PLAN 
 
For treatment or dose modification questions, please contact Drs. Corey J. Langer and 
James L. Wade III at S1400BMedicalQuery@swog.org.  For dosing principles or 
questions, please consult the SWOG Policy #38 "Dosing Principles for Patients on Clinical 
Trials" at http://swog.org (then click on "Policies and Manuals" under the "Visitors" menu 
and choose Policy 38). 
 
7.1 
Pre-Medication and Supportive Care 
 
Premedication associated with standard drug administration and supportive care 
(including anti-diarrheals, antibiotics, diuretics or other medications) may be given 
as indicated by the current American Society of Clinical Oncology (ASCO) 
guidelines. 
 
Patients randomized to docetaxel should pre-medicate with dexamethasone 
beginning 24 hours prior to docetaxel administration.  Dexamethasone may be 
administered per local institutional guidelines.  Recommended dose listed below. 
 
7.2 
Treatment – S1400B 
 
Prior to Revision #3, (Version Date 11/18/15) patients were randomized into one 
of two treatment arms.  As the design and objectives have been modified to a 
Single arm Phase II, followed by a Randomized Phase III, all patients will be placed 
into Arm 1:  GDC-0032 (Taselisib) for the Phase II portion. This section will be 
amended should the trial continue with the Randomized Phase III portion. The 
information regarding the docetaxel treatment plan will remain within the section 
for the patients continuing to receive treatment per protocol.  Patients currently on 
Arm 2, docetaxel will be given the option to re-register to Arm 3, GCD-0032 after 
progressing as defined S1400 Section 10.2d. 
 
a. 
Arm 1:  GDC-0032 (Taselisib) 
 
Agent 
Dose 
Route 
Day 
Schedule* 
 
GDC-0032 
4 mg 
PO 
Daily Continuous 
(Taselisib) 
 
* NOTE: A cycle of treatment is 21 days.  Disease assessment must occur 
every 6 weeks.  Treatment will continue until any of the criteria in Section 
7.5 is met. 
 
Patients must take the GDC-0032 at the same time of day ± 2 hours, 
unless otherwise instructed and regardless of meals. 

 
b. 
Arm 2:  Docetaxel (Closed to accrual per Revision #3) 
 
Agent 
Dose 
Route 
Day 
Schedule* 
 
Dexamethasone 
8 mg 
Oral, 
0-2 
Q 21 days 
 
BID ** 
beginning  
 
 
24 hours  
 
 
Prior to  
 
 
docetaxel 
 
Docetaxel 
75 mg/m2 
IV 
1 
Q 21 days 
* NOTE: A cycle of treatment is 21 days.  Disease assessment must 
occur every 6 weeks.  Treatment will continue until any criteria in 
Section 7.5 is met. 
** Dexamethasone may be administered per local institutional guidelines.  
Recommended dose listed above. 
 
c. 
Arm 3: Re-Registration Treatment with GDC-0032 (Taselisib) 
 
Upon progression (see Section 10.2d in S1400), patients in Arm 2 may 
be eligible for Re-Registration to receive GDC-0032 as follows 
 
Agent 
Dose 
Route 
Day 
Schedule* 
 
GDC-0032 
4 mg 
PO 
Daily Continuous 
(Taselisib) 
 
* NOTE: A cycle of treatment is 21 days.  Disease assessment must occur 
every 6 weeks.  Treatment will continue until any of the criteria in Section 
7.5 is met. 
 
Patients must take the GDC-0032 at the same time of day ± 2 hours, 
unless otherwise instructed and regardless of meals. 
 
7.3 
Drug Compliance Documentation 
 
Drug compliance for GDC-0032 will be recorded by patients on the Intake Calendar 
(see the S1400 abstract page at www.swog.org). Institutional CRAs will review and 
ascertain patient adherence with protocol therapy at the end of treatment for each 
cycle.  Calendar should be kept in the patient's clinic chart.  Note that the Intake 
Calendar is provided only as a tool for tracking patient compliance. Sites may 
utilize institutional pill diaries or other source documentation in place of the Intake 
Calendar at the discretion of the treating physician. 
 
7.4 
Concomitant Medications to Avoid 
 
Based on in vitro data suggesting that GDC-0032 is metabolized by CYP3A4 the 
following drugs should be avoided.  If use of one of these drugs is necessary, the 
risks and benefits should be discussed with the Study Chair prior to its 
concomitant use with GDC-0032: 
 
• 
Strong/moderate CYP3A4 inhibitors:  atazanavir, ritonavir, indinavir, 
nelfinavir, 
saquinavir, 
clarithromycin, 
telithromycin, 
erythromycin, 
troleandomycin, flutonazole, itraconazole, ketoconazole, voriconazole, 
posaconazole, 
aprepitant, 
conivaptan, 
fluvoxamine, 
diltiazem, 

nefazodone, mibefradil, verapamil, and grapefruit juice or grapefruit 
supplements. 
 
• 
Strong/moderate CYP3A4 inducers:  rifampin, carbamazepine, phenytoin, 
oxcarbazepine, phenobarbital, efavirenz, nevirapine, etravirine, modafinil, 
hyperforin (St. Johns Wort), and cyproterone. 
 
• 
Strong/moderate CYP2D6 inhibitors: bupropion, fluoxetine, paroxetine, 
quinidine, cinacalcet, duloxetine, and terbinafine 
 
7.5 
Criteria for Removal from Protocol Treatment 
 
a. 
Progression of disease or symptomatic deterioration (as defined in 
Sections 10.2d and 10.2e of S1400). 
 
* Upon progression, the S1400 Request for New Sub-Study Assignment 
Form may be submitted to receive a new sub-study assignment (see 
Section 14.0). 
 
b. 
Arm 2 (docetaxel) only: If patient has documented progression (as defined 
in Section 10.2d in S1400), patient may continue to Re-Registration to 
receive GDC-0032. Patient would then be removed from re-registration 
protocol treatment upon subsequent progression of disease or 
symptomatic deterioration (as defined in Section 10.2d or 10.2e in S1400).   
 
c. 
Unacceptable toxicity. 
 
d. 
Treatment delay for any reason > 28 days (or as noted in Section 8.0). 
 
e. 
The patient may withdraw from this study at any time for any reason. 
 
7.6 
Discontinuation of Treatment 
 
All reasons for discontinuation of treatment must be documented in the Off 
Treatment Notice. 
 
7.7 
Follow-Up Period 
 
Patients will be followed until death or 3 years after sub-study registration, 
whichever occurs first. Patients registered to Step 2 (Re-Registration) will be 
followed until death or 3 years after Step 2 re-registration. 
 
Note: Patients that enroll on a new sub-study following progression may 
discontinue follow-up on this sub-study and proceed per protocol of new sub-study. 
 
8.0 
TOXICITIES TO BE MONITORED AND DOSE MODIFICATIONS 
 
8.1 
NCI Common Terminology Criteria for Adverse Events 
 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse 
Events) Version 4.0 for toxicity and Serious Adverse Event reporting.  A copy of 
the CTCAE Version 4.0 can be downloaded from the CTEP home page 
(http://ctep.cancer.gov).  All appropriate treatment areas should have access to a 
copy of the CTCAE Version 4.0. 

 
8.2  
General Considerations 
 
a. 
Missed doses for the oral drugs are to be omitted rather than made up. 
 
b. 
If multiple toxicities are experienced, dose modifications will be based on 
the toxicity requiring the largest dose reduction. 
 
c. 
Reductions are based on the dose given in the preceding reporting period 
and are based on toxicities observed since the prior toxicity evaluation. 
 
d. 
Once dose is reduced, patients will continue at the new dose. No dose re-
escalations are allowed. 
 
e. 
A maximum of two dose reductions are allowed. 
 
8.3 
Dose Modifications GDC-0032 (Taselisib) 
 
DRUG 
DOSE LEVEL 
DOSE 
 
GDC-0032 
Full 
 
4 mg tablet QD 
(Taselisib) 
-1 Level 
2 mg tablet QD 
 
-2 Level a 
2 mg tablet QOD b 
 
QD = once daily; QOD = every other day. 
a If the patient continues to experience specified drug related adverse events after 
dose reduction, patient must be removed from protocol therapy. 
b GDC-0032 will be administered on Days 1−21 of the 21-day cycle.  For the 
second dose reduction, dosing will be converted to 2 mg tablet QOD, in which 
case GDC-0032 may be given on two consecutive days during the transition 
from one cycle to the next specifically on the last day of one cycle and the first 
day of the next cycle. 
 
Management of Toxicities 
 
The dose delay and reduction instructions provided in Tables 1−6 are intended to 
serve as recommended guidelines to allow ongoing treatment for patients 
experiencing clinical benefit without signs or symptoms of progression while 
ensuring patient safety.   
 
Due to the approximately 40 hour half-life for GDC-0032, investigators should 
consider holding GDC-0032 for certain Grade 2 toxicities until the adverse events 
resolves to Grade ≤ 1 as discussed below (e.g., stomatitis/oral mucositis, rash, 
diarrhea).  Certain toxicities have occurred within 1−2 weeks of holding or 
discontinuing GDC-0032 drug (e.g., pneumonitis, colitis, rash).  In these cases, the 
adverse event eventually resolved.  Investigators should follow management 
guidelines for toxicities as described below including administration of topical or 
systemic corticosteroids as appropriate. 
 
a. 
Management of Hyperglycemia 
 
Metformin is the first antihyperglycemic medication of choice because of 
the lower risk of hypoglycemia with this agent.  Because metformin in 
some patients may cause diarrhea and not be well tolerated, other 
antihyperglycemic medications such as sulfonylureas (e.g., glimepiride, 
glipizide) can be used.  Extra caution must be used with other drugs such 

as sulfonylureas because of the increased risk for hypoglycemia with 
these agents.  Consultation with an endocrinologist can be helpful in 
managing hyperglycemia. 
 
Table 1. Dose Modification and Management Guidelines for 
Hyperglycemia 
Dose Modification and Management Guidelines 
Eligibility 
and 
monitoring 
• Monitoring: fasting glucose and HbA1C at baseline 
and at certain intervals 
• Instruct patients to report symptoms such as thirst, 
blurred vision and frequent urination 
• Grade ≥ 3 hyperglycemia identified as adverse 
event of special interest (AESI) hence requiring 
expedited reporting from study sites regardless of 
regulatory seriousness   
Grades 1 or 
2 
• Initiation of or an increase in the dose of an anti-
hyperglycemic 
agent 
(e.g., 
metformin) 
and 
additional 
glucose 
monitoring 
must 
be 
implemented.   
• Dosing with GDC-0032 may either be held or 
continued per Investigator evaluation. 
 
Dose Modification and Management Guidelines 
Grade 3  
(asymptomatic) 
• GDC-0032 dosing must be held and the patient 
should be managed per institutional standard of 
care, including implementation of additional 
glucose monitoring and initiation of or an 
increase in the dose of an anti-hyperglycemic 
therapy (e.g., metformin).   
• If the hyperglycemic event improves to Grade ≤ 
1, GDC-0032 dosing may resume at one dose 
level lower. 
Grade 3  
(symptomatic)*, 
Grade 3 (requiring 
hospitalization),  or 
Grade 4 
• GDC-0032 dosing must be held and the patient 
should be managed per institutional standard of 
care, including implementation of additional 
glucose monitoring and initiation of or an 
increase in the dose of anti-hyperglycemic 
therapy.   
If the hyperglycemic event improves to Grade ≤ 
1, GDC-0032 dosing may resume at one dose 
level lower, 
For recurrent symptomatic Grade 3 or Grade 4 
hyperglycemic event, GDC-0032 must be 
permanently discontinued and removed from 
protocol treatment.   
* Symptoms of hyperglycemia include blurry vision, polydipsia, and 
polyuria. 
 
b. 
Management of Pneumonitis 
 

Patients must be assessed for pulmonary signs and symptoms throughout 
the study.  Patients must also have CT scans of the chest at every tumor 
assessment.  Oxygen saturation by pulse oximetry must be measured at 
every visit as part of the assessment of vital signs.  Management 
guidelines for patients with possible pneumonitis are listed in Table 2.  
 
 

Table 2: Dose Modification and Management Guidelines for 
Pneumonitis  
 
 
 
 
 
 
 
 
 
 
Grade 
Intervention 
Investigations 
GDC-0032   
Dose Adjustment 
1 
No specific 
therapy required. 
CT scan.  Consider 
PFTs. Repeat CT scan 
every 8 weeks until 
return to baseline. 
No change. 
2 
Symptomatic 
only.  Prescribe 
corticosteroids if 
cough is 
troublesome. 
CT scan.  Repeat 
CT scan every 
4 weeks until return to 
baseline.  Consider 
PFTs and 
bronchoscopy. 
Reduce dose until 
improvement to 
Grade ≤ 1; consider 
interruption if symptoms 
are troublesome. 
Interrupt treatment as 
long as corticosteroids 
are being given. 
Restart GDC-0032  at 
the same dose if clinical 
benefit evident.  
Consider restarting at 
reduced dose if 
recurrent event or per 
discussion with Study 
Chair. 
Discontinue and remove 
from protocol treatment 
if recovery to Grade ≤ 1 
is not evident within 
28 days. 
3 
Prescribe 
corticosteroids if 
infectious 
etiology is ruled 
out.  Taper as 
clinically 
indicated. 
CT scan.  Repeat 
CT scan every 
4 weeks until return to 
baseline.  Consider 
PFTs. Bronchoscopy 
is recommended. 
Interrupt treatment until 
improvement to 
Grade ≤ 1. 
Restart therapy within 
28 days at a reduced 
dose if clinical benefit is 
evident. 
Interrupt treatment as 
long as corticosteroids 
are being given. 
Grade 
Intervention 
Investigations 
GDC-0032   
Dose Adjustment 
4 
Prescribe 
corticosteroids 
if infectious 
etiology is ruled 
out.  Taper as 
clinically 
indicated. 
CT scan.  Repeat 
CT scan every 
4 weeks until return 
to baseline.  
Consider PFTs. 
Bronchoscopy is 
recommended. 
Discontinue and 
remove from protocol 
treatment. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c. 
Management of Rash 
 
Rash and other dermatological events should be closely monitored, and 
patients with severe rash should be monitored for associated signs and 
symptoms such as fever and hypotension that may be suggestive of a 
systemic hypersensitivity reaction.  For severe rash, dosing of GDC-0032 
must be interrupted, and patients should be treated with supportive 
therapy per standard of care.  Use of antihistamines, as well as topical or 
systemic corticosteroids, may be considered (see Table 3).   
 
Table 3: Dose Modification and Management Guidelines for Rash 
Grade 
of Rash 
Dose Modification and Management Guidelines  
Grade 1 
• 
Continue dosing at current dose and monitor for 
change in severity 
• 
Consider prescribing topical corticosteroids a 
Grade 2 
• 
Interrupt GDC-0032 treatment  
• 
Treat rash with topical corticosteroids. a  
• 
Consider treatment of rash with oral corticosteroids.   b 
• 
Interrupt GDC-0032 treatment as long as oral 
corticosteroids are being given 
• 
If rash improves to Grade ≤ 1 and upon completion of 
any systemic corticosteroids, resume GDC-0032 
treatment at the same dose.   
• 
For recurrent Grade 2 rash, resume GDC-0032 
treatment at one dose level lower. 
Grade 3  
• 
Interrupt GDC-0032 treatment  
• 
Treat rash with topical corticosteroids and/or systemic 
corticosteroids (oral or IV).  
• 
Interrupt GDC-0032 treatment as long as systemic 
corticosteroids are being given 
• 
Consider dermatological consultation and skin biopsy 
Table modified from White et al. 2010.  
CT = computed tomography; PFT = pulmonary function test 
PFTs include tests for DLCO and room air oxygen saturation at rest 
(pulse oximetry).   
PFTs may be useful to monitor the effect of interventions such as dose 
reduction/discontinuation and corticosteroids, in conjunction with 
imaging (White et al. 2010). 

Grade 
of Rash 
Dose Modification and Management Guidelines  
• 
Obtain photographs of rash if permitted by local 
regulations 
• 
If rash improves to Grade ≤ 1 and upon completion of 
any systemic corticosteroids, resume GDC-0032 
treatment at one dose level lower.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
d. 
Management of Gastrointestinal Toxicity 
 
Management of Diarrhea and Colitis 
 
Patients should be closely monitored for gastrointestinal symptoms 
(e.g., nausea, vomiting, diarrhea, colitis, abdominal pain, stomatitis, and 
changes in stool, including checking for blood in stool if clinically 
indicated).  Patients should be advised to inform the investigator if any 
diarrhea occurs, even if it is mild.  Gastrointestinal symptoms should be 
managed per protocol guidelines and institutional standard of care.  For 
example, prompt management of diarrhea with antidiarrheal medications 
must be implemented.  Because of the approximately 40 hour half-life of 
GDC-0032, investigators must hold GDC-0032 for Grade ≥ 2 diarrhea until 
it improves to Grade ≤ 1.   
 
Specific dose modification and management guidelines for diarrhea and 
colitis are provided in Table 4.  
 
Table 4: Dose Modification and Management Guidelines for 
Diarrhea or Colitis 
 
Dose Modification and Management Guidelines  
Grade 1 
• 
Manage per institutional standard of care with 
antidiarrheals1 
• 
For Grade 1 diarrhea occurring after Cycle 2 that 
persists > 5 days despite treatment with anti-diarrheal 
agents, obtain stool culture for infectious workup b.  
Infections (e.g., Clostridium difficile, enteric bacteria, 
CMV) should be treated with the appropriate antibiotic. 
Grade 
of Rash 
Dose Modification and Management Guidelines  
Grade 4 
• 
Permanent discontinuation of GDC-0032 treatment 
and remove from protocol treatment.   
• 
Treat with topical corticosteroids and/or systemic 
corticosteroids.  
• 
Consider dermatological consultation and skin biopsy 
• 
Obtain photographs of rash if permitted by local 
regulations 
AE = adverse event. 
a   Suggested topical steroids include, hydrocortisone 2.5% to face 
twice daily, triamcinolone 0.1% or fluocinonide 0.1% cream to body 
bid. 
b   
Suggested oral steroids include methylprednisolone dose pack or 
prednisone 60 mg daily followed by a taper (e.g., 60 mg for 2 days, 
40 mg for 2 days, 20 mg for 2 days, etc.). 
 

Dose Modification and Management Guidelines  
• 
For non-infectious diarrhea, consider holding GDC-0032 
and treating with a corticosteroid taper (20−40 mg 
prednisone PO QD starting dose) or budesonide 9 mg 
PO QD.  Upon completion of corticosteroid treatment, 
resume GDC-0032 dosing at same dose or one dose 
level lower per investigator evaluation. 
Dose Modification and Management Guidelines  
Grade 2  
• 
Hold GDC-0032 and initially manage with anti-diarrheal 
agents  
a.  Obtain stool culture for infectious workup  
b.   Infections (e.g., Clostridium difficile, enteric bacteria, 
CMV) should be treated with the appropriate antibiotic. 
• 
For non-infectious Grade 2 diarrhea that has not 
improved to Grade ≤ 1 despite 48 hours of anti-diarrheal 
treatment or for Grade 2 colitis, treat with corticosteroid 
taper (20−40 mg prednisone PO QD starting dose) or 
budesonide 9 mg PO QD.  Steroid dosage can be 
increased if diarrhea does not improve. 
• 
If diarrhea or colitis does not improve after 48 hours of 
corticosteroid treatment, a colonoscopy should be 
considered to evaluate for other causes of diarrhea 
(e.g., CMV colitis).  
• 
If Grade 2 diarrhea occurred after Cycle 2 or improved 
with corticosteroid treatment or for Grade 2 colitis, 
resume GDC-0032 dosing at one dose level lower upon 
improvement to Grade ≤ 1 and after completion of any 
corticosteroid taper. 
• 
If Grade 2 diarrhea occurred before Cycle 2 and did 
not require corticosteroid treatment, resume GDC-
0032 dosing at the same dose level or one dose level 
lower per investigator evaluation upon improvement to 
Grade ≤ 1. 
For recurrent Grade 2 diarrhea, resume GDC-0032 dosing at 
one dose level lower upon improvement to Grade ≤ 1 
Grade 3  
• 
Hold GDC-0032 dosing and initially manage with anti-
diarrheal agents  
a.  Obtain stool culture for infectious workup  
b.  Infections (e.g., Clostridium difficile, enteric bacteria, 
CMV) should be treated with the appropriate antibiotic.For 
non-infectious Grade 3 diarrhea, treat with systemic 
corticosteroids (IV solumedrol 16-20mg q8hr or 
Prednisone 60-80mg QD equivalent to start).  Can 
increase steroid dosage if diarrhea does not improve. 2 
• 
For non-infectious Grade 3 diarrhea or colitis, treat with 
systemic corticosteroids (IV solumedrol 16−20 mg every 
8 hours or prednisone 60−80 mg PO QD equivalent to start).  
Can increase steroid dosage if diarrhea does not improve.If 
diarrhea improves to Grade ≤1 and upon completion of any 
steroid taper, resume GDC-0032 treatment at one dose level 
lower.  
• 
Consider colonoscopy as part of further gastrointestinal 
workup.  If diarrhea does not improve after 48 hours of 
corticosteroid treatment, a colonoscopy should be 
considered to evaluate for other causes of diarrhea (e.g., 
CMV colitis). 
• 
If diarrhea or colitis improves to Grade ≤ 1 and upon 
completion of any steroid taper, resume GDC-0032 dosing at 
one dose level lower. 

Dose Modification and Management Guidelines  
• 
Patients with recurrent Grade 3 diarrhea or colitis must be 
permanently discontinued from GDC-0032 and removed 
from protocol therapy. 
Dose Modification and Management Guidelines (contd) 
Grade 4 
• 
Permanent discontinuation of GDC-0032 treatment and 
remove from protocol therapy. Manage as per Grade 3 
diarrhea guidelines. 
1    
  Suggested antidiarrheals include the following: 
a. loperamide (initial: 4 mg, followed by 2 mg after each loose stool, up 
to 16 mg/day) 
b. diphenoxylate and atropine (Diphenoxylate 5 mg 4 times/day until 
control achieved [maximum:  20 mg/day], then reduce dose as 
needed; some patients may be controlled on doses of 5 mg/day 
2  
 Non-infectious diarrhea can be diagnosed by stool culture with workup 
for various enteric bacteria, C. difficile, and CMV. 
 
Management of Stomatitis and Oral Mucositis 
 
Aggressive mouth care for oral mucositis and stomatitis with mouthwash 
formulations (e.g., combinations of local anesthetic, antihistamine, 
corticosteroid, antacid, antifungal and/or antibiotics) may also be helpful in 
managing symptoms, and it is recommended that these are implemented 
with early signs of dry mouth, Grade 1 mucositis, or Grade 1 stomatitis 
(see Table 5).  Examples of mouth care include rinsing with nonalcoholic 
mouthwash, flossing after each meal, using a mild toothpaste and soft-
bristled toothbrush, and avoiding agents containing hydrogen peroxide, 
iodine, and thyme derivatives.  It may also be helpful to advise patients to 
avoid foods that are spicy, acidic, or salty. 
 
Table 5: Dose Modification and Management Guidelines for 
Stomatitis and Oral Mucositis 
 
Grade of 
Stomatitis/Mucositis 
Dose Modification and Management 
Guidelines 
All grade  
• 
Aggressive mouth care that includes 
mouthwash formulations (e.g., combinations 
of local anesthetic, antihistamine, 
corticosteroid, antacid, antifungal and/or 
antibiotics) may be implemented to help 
manage symptoms 
• 
Diet management (e.g., avoidance of spicy 
foods) 
Grade 1 
• 
Monitor symptoms and initiate management 
(see above). Re-evaluate within 48 to 72 
hours.   
Grade 2 
• 
Interrupt GDC-0032 treatment and manage 
until Grade ≤ 1.   
• 
If stomatitis/mucositis improves to Grade ≤ 1, 
resume GDC-0032 at the same dose.   
• 
For recurrent Grade 2 stomatitis or mucositis, 
resume GDC-0032 treatment at one dose 
level lower. 
Grade 3  
• 
Interrupt GDC-0032 treatment and manage 
until Grade ≤ 1.  
• 
If stomatitis/mucositis improves to Grade ≤ 1, 
resume GDC-0032 at one dose level lower.   

Grade of 
Stomatitis/Mucositis 
Dose Modification and Management 
Guidelines 
Grade 4 
• 
Permanent discontinue GDC-0032 treatment 
and remove from protocol therapy. 
 
e. 
Management of Asymptomatic Lipase and/or Amylase Elevations 
 
Some patients treated with GDC-0032 have experienced asymptomatic 
lipase and/or amylase elevations in blood tests without any clinical or 
radiographic symptoms of pancreatitis or another clear etiology for the 
abnormal lab values.  Upon discussion with Study Chair and after a risk-
benefit assessment, investigators can consider continuing GDC-0032 
therapy in such patients at the same dose or one dose level lower.  
Investigators will have a low threshold for interrupting GDC-0032 for any 
concerning clinical gastrointestinal toxicities. 
 
f. 
Management of Other Clinically Significant Adverse Events 
 
See Table 6 for the dose modifications for other clinically significant 
adverse events. 
 
Table 6: Dose Modification and Management Guidelines for Other 
Clinically Significant Adverse Events 
 
Grade 
GDC-0032  
Grade 3: first event 
Hold GDC-0032 until Grade ≤ 1.  
Consider restarting at next lower dose. 
Grade 3: recurrent 
Grade 4, non-life-
threatening 
Hold GDC-0032 until Grade ≤ 1.  
Restart at next lower dose. 
Grade 4, life-
threatening 
Permanently discontinue GDC-0032 and 
remove from protocol therapy.  
 
8.4 
Dose Modifications – Docetaxel (Closed to accrual per Revision #3) 
 
DRUG  
DOSE LEVEL* 
DOSE 
 
Docetaxel    
Full 
75 mg/m2 
 
-1 Level 
55 mg/m2 
   
-2 Level 
35 mg/m2 
 
* Only two docetaxel dose reductions are allowed. 
 
Dose Modifications of Docetaxel 
Hematological Toxicity 
 
Grade 4 Febrile Neutropenia 
Hold docetaxel until recovery to ≤ Grade 1. Then 
resume docetaxel administration with one dose level 
reduction. 
Grade 4 Neutropenia 
Must undergo a dose reduction for subsequent cycles 
regardless of the duration of the neutropenia with a 
maximum of two dose reductions. 
 
Grade 4 Thrombocytopenia 
Hold docetaxel until recovery to ≤ Grade 1. Then 
resume docetaxel administration with one dose level 
reduction. 
 
Hepatic Toxicity 
 

Grade ≥ 3 
Hold docetaxel up to two weeks. If recovered to ≤ 
Grade 1, resume treatment at one level dose 
reduction. 
Otherwise, 
remove 
from 
protocol 
treatment. 
 
Grade  2 
Reduce docetaxel at a one level dose reduction. 
Non-Hematological Toxicity 
 
Grade 4 Vomiting 
If occurs despite antiemetic prophylaxis, restart 
treatment after recovery to ≤ Grade 1 at a one level 
dose reduction. 
 
Grade ≥ 3 Diarrhea 
If occurs despite antidiarrheal treatment, restart 
treatment after recovery to ≤ Grade 1 at a one level 
dose reduction. 
 
Grade 2 Peripheral 
Neuropathy 
Grade 3 Peripheral 
Neuropathy 
One dose level reduction. 
 
Remove from protocol treatment. 
Grade 3 Fluid Retention 
Hold docetaxel until recovery to ≤ Grade 1, then 
restart treatment at a one level dose reduction. 
 
Grade ≥ 3 Stomatitis 
Hold docetaxel until recovery to ≤ Grade 1, then 
restart treatment at a one level dose reduction. 
For All Other Non-
Hematological Toxicities 
Actions 
Grade > 3 
Hold docetaxel until recovery to ≤ Grade 1, then 
restart treatment at a one level dose reduction. 
 
a. 
Hypersensitivity Reactions 
 
No dose reductions will be made for any hypersensitivity reactions. If, 
despite dexamethasone pre-treatment, the patient experiences a 
hypersensitivity reaction, treatment should be as indicated in the following 
table. 
 
 
 
 
 
 
 
 
 
 
In case of late occurring hypersensitivity symptoms, e.g., appearance 
within 1 week of treatment of a localized or generalized pruritis, 
symptomatic treatment may be given (e.g., oral antihistamine).  Additional 
Grade 1: 
• Consider decreasing the rate of infusion until recovery to < 
Grade 1. 
• Then, resume infusion at the initial planned rate. 
Grade 2: 
• Stop docetaxel infusion and give diphenhydramine 50 mg 
IV with or without dexamethasone 10 mg IV. 
• Resume docetaxel infusion after recovery < Grade 1; 
depending on the physician’s assessment of the patient, 
docetaxel infusion should be resumed at a slower rate (e.g., 
infuse at an 8-hour rate for 5 minutes, then at a 4-hour rate 
for 5 minutes, then at a 2-hour rate for 5 minutes, then 
finally, resume at the hour infusion rate). 
• Depending on the intensity of the reaction observed, 
additional oral or IV premedication with an antihistamine 
should also be given for the next cycle of treatment, and 
the rate of infusion should be decreased initially and then 
increased back to the recommended 1-hour infusion, (e.g., 
infuse at an 8-hour rate for 5 minutes, then at a 4-hour rate 
for 5 minutes, than at a 2-hour rate for 5 minutes, and 
finally, administer at the 1-hour infusion rate) 
Grade ≥ 3 
• REMOVE FROM PROTOCOL TREATMENT 

oral or IV premedication with antihistamine may also be given for the next 
cycle of treatment depending on the intensity of the reaction observed.   
 
b. 
Fluid Retention 
 
If symptomatic, patients developing fluid retention may be treated with 
diuretics at the treating investigator’s discretion. Spironolactone at a 
starting dose of 25 mg TID plus furosemide 20-40  mg PRN is 
recommended. 
 
c. 
Hepatic Dysfunction 
 
Patients who develop abnormal liver function tests for any reason while on 
the study will have the following dose reductions: 
 
Dose Modifications for Abnormal Liver Function 
 
Bilirubin 
Alkaline 
Phosphatase 
AST 
or ALT 
Action 
> IULN or 
> 2.5 x IULN or 
> 1.5 x IULN 
Wait ≤ 2 weeks. If 
recovered*, 
retreatment should 
be at one level dose 
reduction.  If not, 
remove from 
protocol treatment. 
* Bilirubin ≤ IULN AND alkaline phosphatase ≤ 2.5 x IULN, AND AST or 
ALT ≤ 1.5 x IULN. 
 
Note: A maximum of two dose reductions per patient are allowed.  
IULN = institutional upper limit of normal. 
 
d. 
Stomatitis 
 
If stomatitis is present on Day 1 of any cycle, treatment should be withheld 
until the stomatitis has resolved. 
 
e. 
Other Non-hematological Toxicities 
 
Manage toxicities ≤ Grade 2 symptomatically, if possible, and retreat 
without dose reduction. 
 
If toxicities ≥ Grade 3, drug should be held until resolution to ≤ Grade 1, 
then reinstituted, if medically appropriate, with a one level dose reduction.  
 
Unacceptable toxicity from docetaxel is defined as one or more of the 
following: 
 
Grade ≥ 3 nonhematologic toxicity (excluding nausea and vomiting) 
despite 2 prior dose reductions 
 
Severe fluid retention not responsive to symptomatic therapy or dose 
reduction 
 
Grade 4 vomiting despite antiemetics and dose reductions 
 

Grade 4 hematologic toxicity despite two prior dose reductions.  However, 
Grade 4 neutropenia must be either > 7 days in duration or must be 
accompanied by fever (single elevation in oral temperature > 38.5°C) 
requiring parenteral antibiotics or with documented infection to be 
considered an unacceptable toxicity (despite two prior dose reductions. 
 
8.5 
Dose Modification Contacts 
 
For treatment or dose modification questions, please contact Drs. Corey J. Langer 
and James L. Wade III at S1400BMedicalQuery@swog.org.  For dosing principles 
or questions, please consult the SWOG Policy #38 "Dosing Principles for Patients 
on Clinical Trials" at http://swog.org (then click on "Policies and Manuals" under 
the "Visitors" menu and choose Policy 38). 
 
8.6 
Adverse Event Reporting 
 
Toxicities (including suspected reactions) that meet the expedited reporting criteria 
as outlined in Section 16.0 of the protocol must be reported to the Operations 
Office, Study Coordinator and NCI via CTEP-AERS, and to the IRB per local IRB 
requirements. 
 
 
 
 
 

 
9.0 
STUDY CALENDAR 
 
9.1  
Arm 1 GDC-0032 (Taselisib) 
 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Subsequent 
Cycles β 
At 
Off 
Tx 
Off Tx 
Follow-
Up 
Prior to 
Prog ∆ 
Off Tx 
Follo
w-Up 
After 
Prog 
√ 
REQUIRED STUDIES 
PRE-
STUDY 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
5 
Wk 
6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Wk 
11 
Wk 
12 
Wk 
13 
Wk 
14 
Wk 
15 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PHYSICAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
History & Physical 
Exam 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
 
Weight & Performance 
Status 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
 
Disease Assessment  Ω 
X 
 
 
 
 
 
 
XΩ 
 
 
 
 
 
XΩ 
 
 
 
XΩ 
 
Toxicity Notation 
 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X ȸ 
X ȸ 
Smoking Status 
Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
LABORATORY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC/Diff/Platelets/Hgb 
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
Serum Bilirubin 
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
ALT or AST 
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
Serum Creatinine/Calc 
CrCl 
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
HbA1c   
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Fasting Glucose   
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
Lipase & Amylase   
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
LDH ¥ 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Albumin ¥ 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X-RAYS AND SCANS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT or MRI for Disease 
Assessment  Ω 
X 
 
 
 
 
 
 
XΩ 
 
 
 
 
 
XΩ 
 
 
 
XΩ 
 
Brain CT/MRI 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Image Submission  Σ 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
Calendar continued on next page.  Click here for footnotes. 
 
 

Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Subsequent 
Cycles β 
At 
Off 
Tx 
Off Tx 
Follow-
Up 
Prior to 
Prog ∆ 
Off Tx 
Follow-
Up 
After 
Prog √ 
REQUIRED STUDIES 
PRE-
STUDY 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
5 
Wk 
6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Wk 
11 
W
k 
12 
Wk 
13 
Wk 
14 
W
k 
15  
SPECIMEN 
SUBMISSION 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tissue for Banking  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X§ 
Blood for Banking  ƒ 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
Xð 
TREATMENT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Arm 1: (21 day cycle) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GDC-0032 (Taselisib) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
NOTE:  Forms are found on the protocol abstract page of the SWOG website (www.swog.org).  Forms submission guidelines are found in Section 
14.0. 
NOTE:  Unless indicated otherwise in the protocol, scheduled procedures and assessments (treatment administration, toxicity assessment for 
continuous treatment, disease assessment, specimen collection and follow-up activities) must follow the established SWOG guidelines as outlined 
in https://swog.org/Visitors/QA/Documents/Best%20Practices%20upddate.pdf.  
 
Footnotes for Calendar 9.1 (GDC-0032): 
Ω  CT or MRI (the same method used at prestudy to meet the eligibility criteria in Section 5.2 of S1400) must be repeated every 6 weeks (± 7 day 
window) until disease progression.   
Σ  Submit scans as outlined in Section 14.0 and Section 15.0 of S1400B. 
β  During continued treatment, items marked under physical and laboratory should be performed at every subsequent cycle, unless otherwise noted.  
Disease assessments are to take place every 6 weeks (± 7 days window). 
Treatment and evaluation will continue until any of the criteria in Section 7.5 of S1400B is met. 
∆  After off treatment prior to progression, patients should be followed by repeating indicated laboratory tests every 3 months or more often as 
clinically indicated for the first year, then every 6 months for up to 3 years from date of sub-study registration.  Disease assessment should 
continue every 6 weeks until progression. 
√ After off treatment and after progression, follow-up will occur (with lab tests and scans performed at the discretion of the treating physician) every 
6 months for 2 years then at end of year 3 from date of sub-study registration. Note: Patients that enroll on a new sub-study following progression 
may discontinue follow-up on this sub-study and proceed per protocol of new sub-study.    
§ With patient’s consent, an additional research biopsy within 1 month after the time of first progression among patients who had a response to 
GDC-0032 (in the opinion of the treating physician) must be collected (see Section 15.0 of S1400B). 
ƒ With patient’s consent additional research blood draws will be collected (see Section 15.0 of S1400B). 
¥ Results of these tests do not determine eligibility but are recommended prior to sub-study registration. 
€ If the pre-study tests are obtained within 14 days prior to treatment, the tests need not be repeated. 
ȸ Assessments should continue until resolution of all acute adverse events. 
ð  Blood for Banking specimen must be collected at first progression after study treatment (see Section 15.0 of S1400B). 

9.2 
Arm 2 Docetaxel 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Subsequent 
Cycles β 
Off Tx 
Follow-
Up 
Prior to 
Prog ∆ 
Off Tx 
Follow-
Up 
After 
Prog √ 
REQUIRED STUDIES 
PRE-
STUDY 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
5 
Wk 
6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Wk 
11 
Wk 
12 
Wk 
13 
Wk 
14 
Wk 
15  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
PHYSICAL 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
History & Physical Exam 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
Weight & Performance Status 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
Disease Assessment  Ω 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
X 
  
  
X 
  
Toxicity Notation 
  
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
Smoking Status Assessment 
X 
X 
LABORATORY 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
CBC/Diff/Platelets/Hgb 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
Serum Bilirubin 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
ALT or AST 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
Serum Creatinine/Calc CrCl 
X 
  
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
HbA1C 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
Fasting Glucose 
X 
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Lipase & Amylase 
X 
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
LDH ¥ 
 
X 
Albumin ¥ 
X 
X-RAYS AND SCANS 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
CT or MRI for Disease 
Assessment  Ω 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
X 
  
  
X 
  
Brain CT/MRI 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
EKG 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Image Submission  Σ 
X 
 
 
 
 
 
 
X 
 
 
 
 
  
X 
  
  
X  
  
SPECIMEN SUBMISSION 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Blood for Banking ƒ 
X 
  
  
  
X 
 
 
X 
 
 
X 
  
  
  
  
  
  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Calendar continued on next page.  Click here for footnotes. 
 
 

Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Subsequent 
Cycles β 
Off Tx 
Follow-
Up 
Prior to 
Prog ∆ 
Off Tx 
Follow-
Up 
After 
Prog √ 
REQUIRED STUDIES 
PRE-
STUDY 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
5 
Wk 
6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Wk 
11 
Wk 
12 
Wk 
13 
Wk 
14 
Wk 
15  
TREATMENT 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Arm 2: (21 day cycle) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Docetaxel 
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
  
Dexamethasone 
 
X 
  
  
X 
  
  
X  
  
  
 X 
  
  
 X 
  
 
 
 
 
NOTE:  Forms are found on the protocol abstract page of the SWOG website (www.swog.org).  Forms submission guidelines are found in Section 
14.0. 
 
Footnotes for Calendar 9.2 (Docetaxel): 
 
Ω  CT or MRI (the same method used at prestudy to meet the eligibility criteria in Section 5.2 of S1400) must be repeated every 6 weeks (± 7 day 
window) until disease progression.   
Σ  Submit scans as outlined in Section 14.0 and Section 15.0 of S1400B. 
β  During continued treatment, items marked under physical and laboratory should be performed at every subsequent cycle.  Disease assessments 
are 
to 
take 
place 
every 
6 
weeks. 
Assessments 
will 
follow 
Best 
Practices 
for 
SWOG 
Studies: 
http://swog.org/Visitors/QA/Documents/Best%20Practices%20upddate.pdf, however the disease assessment window is ± 7 days. 
Treatment and evaluation will continue until any of the criteria in Section 7.5 is met. 
∆  After off treatment prior to progression, patients should be followed by repeating indicated tests every 3 months for the first year, then every 6 
months for up to 3 years from date of sub-study registration. 
√ After off treatment and after progression, follow-up will occur (with lab tests and scans performed at the discretion of the treating physician) every 
6 months for 2 years then at end of year 3 from date of sub-study registration. 
ƒ With patient’s consent, an additional research blood draw must be collected See Section 15.0  of S1400B. 
¥ Results of these tests do not determine eligibility but are recommended prior to sub-study registration. 

9.3  
Arm 3 Re-Registration – GDC-0032 (Taselisib) 
 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Subsequent 
Cycles β 
At 
Off 
Tx 
Off Tx 
Follo
w-Up 
Prior 
to 
Prog 
∆ 
Off Tx 
Follo
w-Up 
After 
Prog 
√ 
REQUIRED 
STUDIES 
Step 2 Re-
Registratio
n  
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
5 
Wk 
6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Wk 
11 
Wk 
12 
Wk 
13 
Wk 
14 
Wk 
15  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PHYSICAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
History & Physical 
Exam 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
 
Weight & 
Performance Status 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
 
Disease Assessment  
Ω 
X 
 
 
 
 
 
 
XΩ 
 
 
 
 
 
XΩ 
 
 
 
XΩ 
 
Toxicity Notation 
 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
X 
Xȸ 
Xȸ 
Smoking Status 
Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
LABORATORY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC/Diff/Platelets/Hg
b 
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
Serum Bilirubin 
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
ALT or AST 
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
Serum 
Creatinine/Calc CrCl 
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
HbA1c   
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Fasting Glucose   
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
Lipase & Amylase   
X 
X€ 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Xȸ 
Xȸ 
LDH ¥ 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Albumin ¥ 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X-RAYS AND 
SCANS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT or MRI for 
Disease Assessment  
Ω 
X 
 
 
 
 
 
 
XΩ 
 
 
 
 
 
XΩ 
 
 
 
XΩ 
 
Brain CT/MRI 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Calendar continued on next page.  Click here for footnotes. 
 
 

Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Subsequent 
Cycles β 
At 
Off 
Tx 
Off Tx 
Follo
w-Up 
Prior 
to 
Prog 
∆ 
Off Tx 
Follo
w-Up 
After 
Prog 
√ 
REQUIRED 
STUDIES 
Step 2 Re-
Registratio
n  
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
5 
Wk 
6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Wk 
11 
Wk 
12 
Wk 
13 
Wk 
14 
Wk 
15  
SPECIMEN 
SUBMISSION 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
Tissue for Banking  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
X§  
Blood for Banking  ƒ 
X 
  
  
  
X 
 
 
X 
 
 
X 
  
  
  
  
  
 
  
Xð 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TREATMENT 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
Arm 3: (21 day cycle) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
GDC-0032 (Taselisib) 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
  
  
NOTE:  Forms are found on the protocol abstract page of the SWOG website (www.swog.org).  Forms submission guidelines are found in Section 14.0. 
NOTE:  Unless indicated otherwise in the protocol, scheduled procedures and assessments (treatment administration, toxicity assessment for continuous treatment, 
disease 
assessment, 
specimen 
collection 
and 
follow-up 
activities) 
must 
follow 
the 
established 
SWOG 
guidelines 
as 
outlined 
in 
https://swog.org/Visitors/QA/Documents/Best%20Practices%20upddate.pdf.  
Footnotes for Calendar 9.3 (Re-Registration GDC-0032): 
Ω  CT or MRI (the same method used at prestudy to meet the eligibility criteria in Section 5.2 of S1400) must be repeated every 6 weeks (± 7 day window) until 
disease progression.   
Σ  Submit scans as outlined in Section 14.0 and Section 15.0 of S1400B. 
β  During continued treatment, items marked under physical and laboratory should be performed at every subsequent cycle, unless otherwise noted.  Disease 
assessments are to take place every 6 weeks. (± 7 days window). 
Treatment and evaluation will continue until any of the criteria in Section 7.5 is met. 
∆  After off treatment prior to progression, patients should be followed by repeating indicated tests every 3 months or more often as clinically indicated for the first 
year, then every 6 months for up to 3 years from date of re-registration. Disease assessment should continue every 6 weeks until progression. 
√ After off treatment and after progression, follow-up will occur (with lab tests and scans performed at the discretion of the treating physician) every 6 months for 2 
years then at end of year 3 from date of re-registration. Note: Patients that enroll on a new sub-study following progression may discontinue follow-up on this sub-
study and proceed per protocol of new sub-study. 
§ With patient’s consent, an additional research biopsy within 1 month after the time of first progression among patients who had a response to GDC-0032 (in the 
opinion of the treating physician) must be collected (see Section 15.0 of S1400B). 
ƒ With patient’s consent additional research blood draws will be collected (see Section 15.0 of S1400B). 
¥ Results of these tests do not determine eligibility but are recommended prior to re-registration. 
€ If the pre-study tests are obtained within 14 days prior to treatment, the tests need not be repeated 
ȸ Assessments should continue until resolution of all acute adverse events 
ð  Blood for Banking specimen must be collected at first progression after study treatment (see Section 15.0 of S1400B). 

 
10.0 
CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS 
 
See Section 10.0 of S1400 for criteria for evaluation and endpoint analysis. 
 
 
11.0 
STATISTICAL CONSIDERATIONS 
 
This study will employ Design #2 the Seamless Phase II followed by Phase III design as 
described in S1400 Section 11.2a.  A complete description of the statistical design and 
analysis plan is included in Section 11.0 of S1400.  This section includes details specific to 
S1400B. 
 
11.1 
Primary Objective and Biomarker Prevalence 
 
Eligibility for S1400B is defined as the presence of any of the following mutations 
(Foundation Medicine [FMI] criteria).  
 
Gene 
Alteration type Eligible alteration (FMI criteria) 
PIK3CA 
Substitution 
R38C, R38H, E81K, R88Q, R93Q, R93W, P104L, 
P104R, G106V, G106R, P104_G106>R, R108H, 
E110del, E110K, K111E, K111N, K111del, G118D, 
V344G, V344M, N345K, N345I, E365K, C378F, 
E418K, C420R, E453K, E453Q, P539R, E542K, 
E542A, E542V, E542G, E542Q, E545A, E545G, 
E545K, E545Q, E545D, Q546E, Q546H, Q546K, 
Q546L, Q546P, Q546R, E726K, G1007R, D1017H, 
Y1021C, Y1021H, T1025A, A1035V, A1035T, 
M1043I, M1043L, M1043V, H1047L, H1047R, 
H1047Y, H1047N, H1047Q, G1049R, G1049S, 
I1058L 
Fusion 
None 
Amplification 
None 
 
The expected prevalence of these PI3K mutations is 9.4% and the expected 
frequency of the other sub-study biomarkers among PI3K positive patients is: 
0.9% for FGFR, 1.9% for CDK, and 1.9% for MET.  Based on simulation using 
the randomization ratios as defined in S1400 Section 11.1, the expected 
frequency of patients assigned to S1400B is 8.0%. 
 
a. 
However, PI3K mutation positivity by Genentech [GNE] criteria (PI3K GNE 
positive) is defined by the presence of a subset of these mutations.  
Specifically, a patient’s tumor is defined as PI3K-positive based on the 
presence of the following mutations: 
 
Gene 
Alteration type GNE criteria 
PIK3CA 
Substitution 
E542K, E545A, E545G, E545K, E545Q, 
H1047L, H1047R, H1047Y 
Fusion 
None 
Amplification 
None 
 
The primary objectives within S1400B are to evaluate GDC-0032 among patients 
defined to be PI3K positive based on the GNE criteria and the FMI criteria.  The 
study sample size and timing of analysis is based on the subset defined to be PI3K 
GNE positive. 
 

11.2 
Sample Size with Power Justification 
 
Phase II Design:  S1400B will follow the Phase II design from the Seamless Phase 
II followed by Phase III (see Section 11.2c of S1400) among patients defined to be 
PI3K GNE positive. 
 
Assuming 72% of PI3K-eligible patients will be PI3K- positive per GNE criteria, the 
total number of patients accrued to S1400B to achieve 40 eligible GNE+ patients 
is 56 eligible patients. Assuming that 5% of patients will be ineligible, the total 
accrual goal to the Phase II study is 59 PI3K-positive patients per FMI criteria (PI3K 
FMI positive). The anticipated duration of accrual to the phase II is 41-51 months 
from study activation. 
 
 
12.0 
DISCIPLINE REVIEW 
 
This section does not apply to this sub-study. 
 
 
13.0 
REGISTRATION GUIDELINES 
 
See Section 13.0 of S1400 for registration guidelines. 
 
13.1 
Registration Timing 
 
Patients must plan to begin treatment within 7 working days after Step 1: sub-study 
registration and Step 2: re-registration. 
 
 
14.0 
DATA SUBMISSION SCHEDULE 
 
14.1 
Data Submission Requirements 
 
Data must be submitted according to the protocol requirements for ALL patients 
registered, whether or not assigned treatment is administered, including patients 
deemed to be ineligible.  Patients for whom documentation is inadequate to 
determine eligibility will generally be deemed ineligible. 
 
14.2 
Master Forms 
 
Master forms can be found on the protocol abstract page on the SWOG website 
(www.swog.org) and (with the exception of the sample consent form and the 
Registration Worksheet) must be submitted on-line via the Web; see Section 14.3 
for details. 
 
14.3 
Data Submission Procedures 
 
a. 
All participating institutions must submit data electronically via the Web 
using Medidata Rave® at the following url: 
https://login.imedidata.com/selectlogin 
 
1. 
If prompted, select the ‘CTEP-IAM IdP’ link. 
 
2. 
Enter your valid and active CTEP-IAM userid and password.  This 
is the same account used for the CTSU members’ web site and 
OPEN. 
 

• 
You may also access Rave® via the SWOG CRA Workbench.  Go to 
the SWOG web site (http://swog.org) and logon to the Members Area 
using your SWOG Roster ID Number and password. After you have 
logged on, click on Workbenches, then CRA Workbench to access the 
home page for the CRA Workbench and follow the link to Rave® 
provided in the left-hand navigation panel. 
 
b. 
To access the CRA Workbench the following must be done (in order): 
 
1. 
You are entered into the SWOG Roster and issued a SWOG 
Roster ID Number, 
 
2. 
You are associated as an investigator or CRA/RN at the institution 
where the patient is being treated or followed, 
 
3. 
Your Web User Administrator has added you as a web user and 
has given you the appropriate system permissions to view data for 
that institution. 
 
For assistance with points 1 and 2 call the Operations Office at 210/614-
8808.  For point 3, contact your local Web User Administrator (refer to the 
"Who is my Web User Administrator?" function on the swog.org Members 
logon page). 
 
For 
difficulties 
with 
the 
CRA 
Workbench, 
please 
email 
technicalquestion@crab.org. 
 
c. 
Institutions participating through the Cancer Trials Support Unit (CTSU) 
please refer to the CTSU Participation Table on Page 5 of S1400. 
 
14.4 
Data Submission Overview and Timepoints 
 
a. 
WITHIN 7 DAYS OF SUB-STUDY REGISTRATION, SUBMIT: 
 
S1400B Onstudy Form 
 
 
Smoking Status Assessment Form 
 
Baseline Tumor Assessment Form (RECIST 1.1) 
 
Radiology reports from all scans performed to assess disease at baseline 
(NOTE: Upload reports via the Source Documentation: Baseline form in 
Rave) 
 
Submit to IROC via TRIAD for Central Radiology Review:  Images from 
scans performed to assess disease at baseline as specified in Section 
15.3. 
 
b. 
WITHIN 7 DAYS AFTER STEP 2 RE-REGISTRATION: 
 
Submit the following: 
 
S1400B Re-Registration Eligibility Verification Form 
 
Baseline Tumor Assessment Form (RECIST 1.1) 
Smoking Status Assessment Form  
 

Radiology reports from all scans performed to assess disease at baseline 
(NOTE: Upload reports via the Source Documentation: Baseline form 
found in the Re-Registration folder form i in Rave) 
 
c. 
IF PATIENT CONSENTS, SUBMIT SPECIMENS: 
 
Specimens as specified in Section 15.0 of S1400B. 
 
d. 
IMMEDIATELY AFTER EACH CYCLE (CYCLE = 21 DAYS) OF 
TREATMENT (INCLUDING BOTH ON INITIAL TREATMENT ARM AND 
RE-REGISTRATION TREATMENT ARM) SUBMIT: 
 
S1400B Treatment Form 
 
S1400B Adverse Event Form 
 
S1400B Laboratory Values Form  
 
For Cycle 1 only: submit the S1400B Pre-Treatment Laboratory Values 
Form   
 
e. 
WITHIN 14 DAYS AFTER EACH DISEASE ASSESSMENT (INCLUDING 
BOTH ON TREATMENT AND OFF TREATMENT PRIOR TO DISEASE 
PROGRESSION) (see S1400B Section 9.0 for Disease Assessment 
Schedule), SUBMIT: 
 
Follow-Up Tumor Assessment Form (RECIST 1.1) documenting results of 
assessment 
 
Radiology reports from all scans performed to assess disease at follow-up 
(NOTE: Upload reports via the Source Documentation: Follow-up form in 
Rave) 
 
Submit to IROC via TRIAD for Central Radiology Review:  Images from 
scans performed to assess disease as specified in Section 15.3. 
 
f. 
WITHIN 7 DAYS OF DISCONTINUATION OF TREATMENT (INCLUDING 
BOTH ON INITIAL TREATMENT ARM AND RE-REGISTRATION 
TREATMENT), SUBMIT: 
 
Off Treatment Notice documenting reasons for off treatment 
 
Smoking Status Assessment Form 
 
S1400B Treatment Form 
 
S1400B Adverse Event Form 
 
S1400B Laboratory Values Form 
 
g. 
ONCE OFF TREATMENT SUBMIT EVERY 6 MONTHS FOR THE FIRST 
2 YEARS FROM S1400B REGISTRATION*, THEN AT THE END OF 
YEAR 3 FROM SUB-STUDY/RE-REGISTRATION * SUBMIT: 
 
Advanced NSCLC Follow-Up Form 
 
Late Effects Form (if prior to treatment for progression or relapse or a 
second primary, and prior to non-protocol treatment, the patient 

experiences any severe [Grade ≥ 3] long term toxicity that has not been 
previously reported). 
*For patients registered to Step 2 (Re-Registration), the follow-up 
schedule is calculated from the date of Step 2 Re-Registration. 
 
Note: Patients that enroll on a new sub-study following progression may 
discontinue follow-up on this sub-study and proceed per protocol of new 
sub-study (See Section 14.4j).    
 
h. 
WITHIN 7 DAYS OF PROGRESSION/RELAPSE (BOTH ON INITIAL 
TREATMENT ARM AND RE-REGISTRATION TREATMENT ARM), 
SUBMIT: 
 
Site(s) of Progression or Relapse Form 
 
Follow-Up Tumor Assessment Form (RECIST 1.1) 
 
Radiology reports from all scans performed to assess disease at follow-up 
(NOTE: Upload reports via the Source Documentation: Follow-up form in 
Rave) 
 
Submit to IROC via TRIAD for Central Radiology Review:  Images from 
scans performed to assess disease as specified in Section 15.3. 
 
i. 
WITHIN 28 DAYS OF KNOWLEDGE OF DEATH: 
 
Submit the Notice of Death documenting death information.  In addition, if 
the patient was still on protocol treatment, submit materials specified in 
Section 14.4e or if patient was no longer on treatment, submit a final 
Advanced NSCLC Follow-Up Form. 
 
j. 
Data Submission FOR PATIENTS WHO HAVE PROGRESSED AND 
WISH TO REGISTER TO A NEW SUB-STUDY: 
 
WITHIN 7 DAYS OF PROGRESSION/RELAPSE: 
 
Submit the S1400 Request for New Sub-Study Assignment Form under 
S1400 in Rave® Continue follow-up on S1400B per Sections 9 and 14.4g 
until registration to a new sub-study. See Section 14.6 of S1400 for 
additional data submission requirements following request for new sub-
study assignment. 
 
15.0 
SPECIAL INSTRUCTIONS 
 
15.1 
SWOG Specimen Tracking System (STS) 
 
See Section S1400 Section 15.1 for SWOG Specimen Tracking System (STS) 
instructions. 
 
15.2  
Correlative Studies and Banking  (Optional for Patients) 
 
Specimens for correlative studies and banking (submitted to the SWOG Specimen 
Repository – Solid Tissue, Myeloma and Lymphoma Division, Lab #201) are 
considered optional for the patient: 
 
a. 
With patient’s consent, specimens must be collected and submitted as 
follows: 
 

1. 
Peripheral Blood: 
 
Specimens must be collected at the following times during both 
Step 1 and Step 2 (Re-Registration): 
 
• 
Pre-study (see Section 15.3 of S1400) 
Note: If a patient provided blood at pre-screening at the time 
of progression on current treatment or screening (see Section 
15.3 of S1400) and registration to S1400 was within 42 days 
from sub-study registration, then that blood specimen can 
count as pre-study blood 
• 
Weeks 4, 7, 10 - Patients that go off treatment are not required 
to continue to submit specimens. 
• 
First Progression after study treatment 
 
Approximately 8-10 mL of blood must be collected in EDTA tubes.  
Blood should be processed within one hour after venipuncture. If 
immediate processing within this time frame is not possible, EDTA 
tubes that are not processed immediately should be refrigerated 
at 4˚C. The approximate time from collection to processing should 
be recorded as part of the patient’s source documentation. EDTA 
tubes must be centrifuged at 800 g for 10 minutes at 4˚C for the 
collection of plasma. Plasma must be transferred to one 15 ml 
centrifuge tube and spun again at 800 g for an additional 10 
minutes. Plasma must then be pipetted into 1 ml coded cryovials 
at 0.5 ml aliquots. Plasma must be clear before freezing; no cells 
or debris should be present. Each buffy coat layer (the gray-white 
layer at the interface of blood cells and plasma, approximately 1 
ml) from the blood tube must each be transferred into 
appropriately labeled 2-ml cryovials.  Samples must be placed 
immediately in a -80˚C freezer to ensure long-term viability.   
 
2. 
New Biopsy of Tumor at Time of Progression among responders 
to GDC-0032: 
 
A new biopsy is strongly requested from patients who responded 
to protocol treatment (in the opinion of the treating physician) and 
then experienced disease progression. Biopsies will be used for 
molecular analysis of molecular characteristics associated with 
mechanisms of resistance.  New biopsy should be either 
bronchoscopy/surgical biopsy or CT guided biopsy. The biopsy 
should be performed within one month after progression and 
should be processed as FFPE material. The minimum 
requirement is a block or 12 unstained sections. 
 
 
b. 
Specimen Submission 
 
Samples for multiple patients can be shipped in batches, at least every 3 
months if not more frequently, to the SWOG Specimen Repository – Solid 
Tissue, Myeloma and Lymphoma Division, Lab #201. 
 
Specimen collection and submission instructions can be accessed on the 
SWOG Specimen Submission webpage  
(http://swog.org/Members/ClinicalTrials/Specimens/STSpecimens.asp). 
 
c. 
Specimen collection kits are not being provided for this submission; sites 
must use institutional supplies. 

 
15.3 
Radiology Review (Required) 
 
CT, PET/CT, and/or MRI images must be locally read and interpreted by the local 
site radiology service.  Imaging exams must then be submitted to the Imaging and 
Radiation Oncology Core (IROC) at Ohio via TRIAD Imaging Submission 
procedures for central data collection and quality control (QC) check as well as 
retrospective central review. 
 
a. 
CT, PET/CT, and/or MRI images must be submitted to IROC Ohio for 
central review at the following timepoints for both Step 1 and Step 2 (Re-
Registration): 
 
• 
Baseline 
• 
Every 6 weeks until progression 
 
All study participants must have a CT (or MR or PET/CT) exam prior to 
sub-study entry.  Participants must then undergo additional imaging every 
6 weeks until progression of disease.  The same imaging modality used 
for the pre-treatment exam must be used for the post-treatment exams 
(see Section 10.1c). Each exam should be performed per Section 18.1c.  
IROC will perform a QC of the imaging exams.   
 
Clinical management and treatment decisions will be made by the treating 
physician based on local site assessments and other clinical appropriate 
considerations. 
 
Central review of scans will not be triggered if the study will not be 
submitted to the FDA for FDA approval of the investigational therapy.  
Central review of scans will be triggered only if deemed necessary for FDA 
evaluation. A detailed description of the central radiology PFS review, 
including 
image 
acquisition 
parameters 
and 
image 
submission 
instructions, can be found in Section 18.1c. 
 
b. 
TRIAD Digital Image Submission  
 
TRIAD is the secure electronic image upload application utilized for IROC 
Services of this trial. TRIAD de-identifies and validates the images as they 
are transferred. 
 
1. 
TRIAD Access Requirements: 
 
TRIAD will be the sole means of image transfer to the IROC Ohio. 
TRIAD should be installed prior to study participant enrollment to 
ensure prompt secure, electronic submission of imaging. 
 
• 
Site staff who submit images through TRIAD will need to be 
registered with the Cancer Therapy Evaluation Program 
(CTEP) and have a valid and active CTEP-IAM account (see 
Section 13.2). 
 
• 
To submit images, the site user must be on the site’s affiliate 
rosters and be assigned the 'TRIAD site user' role on the 
CTSU roster.  Users should contact the site’s CTSU 
Administrator or Data Administrator to request assignment of 
the TRIAD site user role.   
 

2. 
TRIAD Installations: 
 
After a user receives a CTEP-IAM account with the proper user 
role, he/she will need to have the TRIAD application installed on 
his/her workstation to be able to submit images. TRIAD installation 
documentation 
can 
be 
found 
by 
following 
this 
link 
https://triadinstall.acr.org/triadclient/   
 
Questions regarding image submissions, including TRIAD, should be 
directed to SWOG1400@irocohio.org or call IROC Ohio at 614-293-2929. 
 
 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS 
 
16.1 
Adverse Event Reporting Requirements  
 
a. 
Purpose 
 
Adverse event data collection and reporting, which are required as part of 
every clinical trial, are done to ensure the safety of patients enrolled in the 
studies as well as those who will enroll in future studies using similar 
agents. Adverse events are reported in a routine manner at scheduled 
times during a trial. (Directions for routine reporting are provided in Section 
14.0.) Additionally, certain adverse events must be reported in an 
expedited manner to allow for more timely monitoring of patient safety and 
care. The following guidelines prescribe expedited adverse event 
reporting for this protocol.  
 
b. 
Reporting method 
 
This study requires that expedited adverse events be reported using the 
Cancer Therapy Evaluation Program Adverse Event Reporting System 
(CTEP-AERS).  CTEP's guidelines for CTEP-AERS can be found at 
http://ctep.cancer.gov. A CTEP-AERS report must be submitted to the 
SWOG Operations Office electronically via the CTEP-AERS Web-based 
application located at 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/adve
rse_events.htm 
 
 
 
c. 
When to report an event in an expedited manner 
 
Some adverse events require 24-hour notification (refer to Table 16.1) via 
CTEP-AERS. When Internet connectivity is disrupted, a 24-hour 
notification is to be made to SWOG by telephone at 210-614-8808, or by 
email at adr@swog.org.  Once Internet connectivity is restored, a 24-hour 
notification that was made by phone or using adr@swog.org must be 
entered electronically into CTEP-AERS by the original submitter at the 
site. 
 
When the adverse event requires expedited reporting, submit the report 
within the number of calendar days of learning of the event specified in 
Table 16.1 or 16.2, as applicable.  
 
d. 
Other recipients of adverse event reports 
 

The SWOG Operations Office will forward reports and documentation to 
the appropriate regulatory agencies and drug companies as required. 
 
Adverse events determined to be reportable to the Institutional Review 
Board responsible for oversight of the patient must be reported according 
to local policy and procedures. 
 
e. 
Expedited reporting for investigational agents 
 
Expedited reporting is required if the patient has received at least one dose 
of the investigational agent as part of the trial. Reporting requirements are 
provided in Table 16.1. The investigational agent used in Arm 1 and Arm 
3 of this study is GDC-0032.  If there is any question about the reportability 
of an adverse event or if on-line CTEP-AERS cannot be used, please 
telephone or email the SAE Specialist at the Operations Office, 210/614-
8808 or adr@swog.org, before preparing the report. 
 
 

Table 16.1: 
Phase 1 and Early Phase 2 Studies:  Expedited Reporting Requirements for Adverse events that 
Occur on Studies under an Non-CTEP IND within 30 Days of the Last Administration of the 
Investigational Agent/Intervention1 GDC-0032 Arm 1 or Re-Registration, Arm 3. 
  
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE:  Investigators MUST immediately report to the sponsor (NCI) ANY Serious Adverse Events, whether or 
not they are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
 
An adverse event is considered serious if it results in ANY of the following outcomes:   
1) 
Death 
2) 
A life-threatening adverse event  
3) 
An adverse event that 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) 
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. (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the NCI via 
CTEP-AERS within the timeframes detailed in the table below. 
Hospitalization 
Grade 1 and Grade 2 Timeframes 
Grade 3-5 
Timeframes 
Resulting in 
Hospitalization       
≥ 24 hrs 
10 Calendar Days 
24-Hour 5 Calendar 
Days 
Not resulting in 
Hospitalization       
≥ 24 hrs 
Not required 
NOTE:   Protocol specific exceptions to expedited reporting of serious adverse events (if applicable) are 
found in Section 16.1f.  
 
Expedited AE reporting timelines are defined as: 
o “24-Hour; 5 Calendar Days” - The AE must initially be reported via CTEP-AERS within 24 hours of 
learning of the AE, followed by a complete expedited report within 5 calendar days of the initial 
24-hour report. 
 
o 
“10 Calendar Days” - A complete expedited report on the AE must be submitted within 10 
calendar days of learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows:  
 
Expedited 24-hour notification followed by complete report within 5 calendar days for: 
• All Grade 3, 4, and Grade 5 AEs 
Expedited 10 calendar day reports for: 
• Grade 2 AEs resulting in hospitalization or prolongation of hospitalization 
 
May 5, 2011 
 
 
 

f. 
Additional Instructions or Exceptions to CTEP-AERS Expedited 
Reporting Requirements for Late Phase 2 and Phase 3 Studies 
Utilizing an Agent under a non-CTEP-IND: 
 
1) 
Group-specific instructions. 
 
Supporting Documentation Submission - Within 5 calendar days 
submit the following to the SWOG Operations Office by fax to 210-
614-0006 or mail to the address below: 
 
a. 
Printed copy of the first page of the CTEP-AERS report 
b. 
Copies of clinical source documentation of the event 
c. 
If applicable, and they have not yet been submitted to the 
SWOG Data Operations Center, copies of Off Treatment 
Notice and/or Notice of Death. 
 
2) 
The adverse events listed below are considered to be adverse 
events of special interest (AESIs) and require expedited 
reporting for this trial: 
 
• 
Grade ≥ 3 symptomatic hyperglycemia 
• 
Grade ≥ 2 colitis or enterocolitis 
• 
Grade ≥ 2 diarrhea 
• 
Grade ≥ 3 rash 
• 
Grade ≥ 2 pneumonitis 
• 
Grade ≥ 3 stomatitis  
• 
Cases of potential drug-induced liver injury that include an 
elevated ALT or AST in combination with either an elevated 
bilirubin or clinical jaundice, as defined by Hy’s law 
• 
Suspected transmission of an infectious agent by the study 
drug 
 
g. 
Expedited reporting for commercial agents 
 
Commercial reporting requirements are provided in Table 16.2. The 
commercial agent used in Arm 2 of this study is docetaxel. If there is 
any question about the reportability of an adverse event or if on-line 
CTEP-AERS cannot be used, please telephone or email the SAE 
Program at the Operations Office, 210/614-8808 or adr@swog.org, 
before preparing the report. 
 
 

Table 16.2. Expedited reporting requirements for adverse events 
experienced by patients on study Arm 2 who have received the 
commercial drug listed in  Section 16.1g above within 30 days of the last 
administration of the commercial agent. 
 
Attribution 
 
Grade 4 
 
Grade 5a 
Unexpected 
Expected 
Unexpected 
Expected 
Unrelated 
or Unlikely 
 
 
CTEP-
AERS 
CTEP-
AERS 
Possible, 
Probable, 
Definite 
CTEP-AERS 
 
CTEP-
AERS 
CTEP-
AERS 
CTEP-AERS:  Indicates an expedited report is to be submitted via CTEP-AERS 
within 10 calendar days of learning of the eventb. 
a This includes all deaths within 30 days of the last dose of treatment with a 
commercial agent(s), regardless of attribution.  Any death that occurs more than 30 
days after the last dose of treatment with a commercial agent(s) and is attributed 
(possibly, probably, or definitely) to the agent(s) and is not due to cancer recurrence 
must be reported according to the instructions above. 
 
b Submission of the on-line CTEP-AERS report plus any necessary amendments 
generally completes the reporting requirements. You may, however, be asked to 
submit supporting clinical data to the Operations Office in order to complete the 
evaluation of the event. If requested, the specified data should be sent within 5 
calendar days by fax to 210-614-0006.  
 
 
h. 
Reporting Secondary Malignancy, including AML/ALL/MDS 
 
1. 
A secondary malignancy is a cancer caused by treatment for a 
previous malignancy (e.g., treatment 
with 
investigational 
agent/intervention, radiation or chemotherapy). A secondary 
malignancy is not considered a metastasis of the initial neoplasm. 
 
SWOG requires all secondary malignancies that occur following 
treatment with an agent under a Non-NCI IND to be reported via 
CTEP-AERS.  Three options are available to describe the event. 
 
• 
Leukemia secondary to oncology chemotherapy (e.g., 
Acute Myelocytic Leukemia [AML]) 
• 
Myelodysplastic syndrome (MDS) 
• 
Treatment-related secondary malignancy 
 
Any malignancy possibly related to cancer treatment (including 
AML/MDS) should also be reported via the routine reporting 
mechanisms outlined in each protocol. 
 
Second Malignancy: A second malignancy is one unrelated to the 
treatment of a prior malignancy (and is NOT a metastasis from the 
initial malignancy).  Second malignancies require ONLY routine 
reporting via CDUS unless otherwise specified. 
 
 
For more information see: 

http://ctep.cancer.gov/protocolDevelopment/electronic_applicatio
ns/docs/aeguidelines.pdf  
 
2. 
Any supporting documentation should be submitted to CTEP per 
NCI guidelines for AE reporting located at  
http://ctep.cancer.gov/protocolDevelopment/electronic_applicatio
ns/docs/aeguidelines.pdf.  
 
A copy of the report and the following supporting documentation 
must also be submitted to SWOG Operations Office within 30 
days by fax to 210-614-0006 or mail to the address below: 
 
• 
a copy of the pathology report confirming the AML/ALL /MDS 
diagnosis 
• 
(if available) a copy of the cytogenetics report   
 
SWOG 
ATTN: SAE Program 
4201 Medical Drive, Suite 250 
San Antonio, Texas 78229 
 
NOTE: If a patient has been enrolled in more than one NCI-
sponsored study, the report must be submitted for the most recent 
trial. 
 
i. 
Reporting Pregnancy, Fetal Death, and Death Neonatal 
 
1. 
Pregnancy Study participants who become pregnant while on 
study; that pregnancy should be reported in an expedited manner 
via CTEP-AERS as Grade 3 “Pregnancy, puerperium and 
perinatal conditions – Other (pregnancy)” under the 
Pregnancy, puerperium and perinatal conditions SOC.   
 
Additionally, the pregnancy outcome for patients on study should 
be reported via CTEP-AERS at the time the outcome becomes 
known, accompanied by the same Pregnancy Report Form used 
for the initial report. 
 
2. 
Fetal Death Fetal Death defined in CTCAE as “A disorder 
characterized by death in utero; failure of the product of 
conception to show evidence of respiration, heartbeat, or definite 
movement of a voluntary muscle after expulsion from the uterus, 
without 
possibility 
of 
resuscitation” 
should 
be 
reported 
expeditiously as Grade 4 “pregnancy, puerperium and 
perinatal conditions – Other (pregnancy loss)” under the 
Pregnancy, puerperium and perinatal conditions SOC.   
 
3. 
Death Neonatal  Neonatal death, defined in CTCAE as “A 
disorder characterized by cessation of life occurring during the first 
28 days of life” that is felt by the investigator to be at least possibly 
due to the investigational agent/intervention should be reported 
expeditiously.   
 
A neonatal death should be reported expeditiously as Grade 4 
“General disorders and administration – Other (neonatal 
loss)” under the General disorders and administration SOC. 
 

Fetal death and neonatal death should NOT be reported as a 
Grade 5 event.  If reported as such, the CTEP-AERS interprets 
this as a death of the patient being treated. 
 
NOTE:  When submitting CTEP-AERS reports for “Pregnancy, 
“Pregnancy loss”, or “Neonatal loss”, the Pregnancy Information 
Form should also be completed and faxed with any additional 
medical information to 301-230-0159.  The potential risk of 
exposure of the fetus to the investigational agent(s) or 
chemotherapy agent(s) should be documented in the “Description 
of Event” section of the CTEP-AERS report. 
 
The Pregnancy Information Form is available at:  
http://ctep.cancer.gov/protocolDevelopment/adverse_effects.htm    
 
 
 
17.0 
BIBLIOGRAPHY
 
1  
Cantley LC. The phosphoinositide 3-kinase pathway. Science 296(5573):1655−7, 2002. 
 
2  
Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 12:9-22, 2007. 
 
3  
Cantley LC. The phosphoinositide 3-kinase pathway. Science 296(5573):1655−7, 2002. 
 
4  
Shayesteh L, Lu Y, Kuo WL, et al. PIK3CA is implicated as an oncogene in ovarian cancer. Nat 
Genet 21:99−102, 1999. 
 
5  
Massion PP, Taflan PM, Shyr Y, et al. Early involvement of the phosphatidylinositol 3-Kinase/AKT 
pathway in lung cancer progression. Am J Resp Crit Care Med 170:1088−94, 2004. 
 
6  
Wu G, Xing M, Mabbo E, et al. Somatic mutation and gain of copy number of PIK3CA in human 
breast cancer. Breast Cancer Res 7:R609−16, 2005. 
 
7  
Cantley LC. The phosphoinositide 3-kinase pathway. Science 296(5573):1655−7, 2002. 
 
8  
Ward S, Sotsios Y, Dowden J, et al. Therapeutic potential of phosphoinositide 3-kinase inhibitors. 
Chem Biol 10:207−13, 2003. 
 
9  
Cantley LC. The role of phosphoinositide 3-kinase in human disease. In: The Harvey Lectures, 
Series 100, 2004−2005. Hoboken: John Wiley and Sons Inc 103−22, 2006. 
 
10  
Bachman KE, Argani P, Samuels Y, et al. The PIK3CA gene is mutated with high frequency in 
human breast cancers. Cancer Biol Ther 3:772–5, 2004. 
 
 
11  
Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human 
cancers. Science 304:554, 2004. 
 
12  
Karakas B, Bachman KE, Park BH. Mutation of the PIK3CA oncogene in human cancers. Br J 
Cancer 94:455−9, 2006. 
 
13  
Jia S, Liu Z, Zhang S, et al. Essential roles of PI(3)K-p110β in cell growth, metabolism and 
tumorigenesis. Nature 454:776−9, 2008.