Clinical trial NCT01202409
Conditions: Gastrointestinal Cancer
Keywords: Ampulla of Vater Adenocarcinoma of the small bowel Metastatic Kirsten rat sarcoma KRAS Capecitabine Xeloda Oxaliplatin Eloxatin CAPOX Panitumumab Vectibix
Sponsor: M.D. Anderson Cancer Center
Start date: 2010-11-02; Completion date: 2018-07-03
Enrollment: 19 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this clinical research study is to learn if panitumumab can help to control advanced cancer of the small bowel or ampulla of Vater. The safety of this drug will also be studied.

Detailed description:
Panitumumab is designed to "turn off" a protein that is important in cell growth. This may stop the growth of cancer cells.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive the study drug during 14 day study "cycles."

On Day 1 of every cycle, you will receive panitumumab by vein over about 60-90 minutes.

Study Visits:

On or before Day 1 of each cycle:

* You will have a physical exam, including measurement of your weight.
* Your performance status will be recorded.
* You will be asked about any symptoms you may be experiencing and any drugs you may be taking.
* Blood (about 2 tablespoons) will be drawn for routine tests.

Every 4 cycles:

* You will have a chest X-ray or a computed tomography (CT) scan of your chest to check the status of the disease.
* You will have a CT or MRI scan to check the status of the disease. If your scan shows that you are responding to the treatment, you will have another CT or MRI scan 6 weeks later.

Length of Study:

You may continue receiving the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.

End-of-Treatment:

After you stop taking the study drugs for any reason, you will have an end-of-treatment visit. The following tests and procedures will be performed:

* You will have a physical exam, including measurement of your weight.
* Your performance status will be recorded.
* You will be asked about any symptoms you may be experiencing and any drugs you may be taking.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* If the doctor thinks it is needed, you will have a CT or MRI scan of the abdomen and pelvis to check the status of the disease.

Follow-Up:

Thirty (30) days after your last dose of study drug(s), you will be asked about any symptoms you may be experiencing and any drugs you may be taking. If you are unable to come to MD Anderson for this, the study staff will call you and ask you these questions. This call will last about 30 minutes.

You will then be called every 3 months and asked the same questions. Each call will last about 15-30 minutes.

If you are taken off study treatment for reasons other than the disease getting worse, you will have a CT or MRI scan of the abdomen and pelvis to check the status of the disease every 12 weeks (+/- 2 weeks) after the End-of-Treatment visit. This will be done until the disease gets worse and if you do not start any other anti-cancer treatment.

This is an investigational study. Panitumumab is commercially available and FDA approved to treat a certain type of colorectal cancer. Its use in this type of cancer is investigational.

Up to 27 patients will take part in this study. All will be enrolled at MD Anderson.

Arms: arm 1: Starting Dose of Panitumumab: 9 mg/kg by vein over 60 minutes on day 1 of a 14 day cycle.
Interventions: intervention 1: Panitumumab
Intervention descriptions: intervention 1: Starting Dose Level: 9 mg/kg by vein over 60 minutes on day 1 of a 14 day cycle.

Protocol documents:
Prot_SAP_000.pdf: 
2009-0458
December 16, 2014
Abstract - Page 1
Protocol Abstract Page
Phase II Study of Panitumumab in KRAS Wild-type Locally Advanced or 
Metastatic Adenocarcinoma of the Small Bowel or Ampulla of Vater.
2009-0458
Core Protocol Information
Study Chairman: 
Michael Overman
Department:
Gastrointestinal Medical Oncology
Phone:
713-745-4317
Unit:
0426
Full Title: 
Phase II Study of Panitumumab in KRAS Wild-type Locally Advanced or Metastatic 
Adenocarcinoma of the Small Bowel or Ampulla of Vater.
Protocol Phase:
Phase II
Version Status:
Activated -- Closed to new patient entry as of 04/26/2016
Version:
16
Document Status:
Final
Abstract
Objectives:
Primary
To determine the response rate (RR) for patients with Kirsten rat sarcoma (KRAS) 
wild-type locally advanced or metastatic adenocarcinoma of the small bowel or ampulla 
of Vater treated with panitumumab.
Secondary 
1)  To determine the overall progression-free survival (PFS) for panitumumab.
2)  To determine overall PFS for panitumumab in the subset of patients with metastatic 
disease only.
3)  To determine the overall survival (OS) panitumumab.
4)  To determine the OS for panitumumab in the subset of patients with metastatic 
disease only.
5)  To determine the toxicity of panitumumab.
Rationale: (Be as concise as possible)
Adenocarcinoma of the small bowel is a rare cancer that has many molecular, genetic, 
and epidemiological similarities with adenocarcinoma of the large bowel.  In particular 
both cancers demonstrate an identical frequency and pattern of mutations in the KRAS 
oncogene.  The use of anti-epidermal growth factor receptor (anti-EGFR) antibodies, 
such as panitumumab, has demonstrated clear anti-cancer activity in the treatment of 


2009-0458
December 16, 2014
Abstract - Page 2
adenocarcinoma of the colorectum.  Recently, the benefit with anti-EGFR therapy in the 
treatment of colorectal adenocarcinoma has been shown to be limited to the subset of 
patients who have a wild-type KRAS gene.  Given the similarities between 
adenocarcinoma of the small and large bowel, we feel that the lack of activity of 
panitumumab in mutant KRAS colorectal cancer patients, supports the selection of only 
small bowel adenocarcinoma patients with a wild-type KRAS oncogene for treatment 
with CAPOX and panitumumab.  Thus, the selection of only wild-type KRAS patients will 
serve as a molecular enrichment of patients who have the greatest chance of benefit 
from the addition of panitumumab to CAPOX chemotherapy.
Based upon retrospective studies and two prospective studies that have been conducted 
in this tumor type, the general combination of a fluorinated pyrimidine and a platinum 
compound such as CAPOX or FOLFOX represents the current standard of care 
approach for adenocarcinoma of the small bowel and ampulla of Vater.    
 
We have recently completed a phase II study of capecitabine combined with oxaliplatin, 
CAPOX, in the treatment of SBA and AAC. This single institution study conducted at 
M.D. Anderson Cancer Center enrolled 31 patients with metastatic or unresectable 
disease.  The overall response rate was 52%. 
 
The combination of CAPOX chemotherapy with the anti-EGFR antibody cetuximab has 
been explored in two phase II studies.  Panitumumab is an anti-EGFR monoclonal 
antibody of the IgG2 isotype that was approved by the US Food and Drug Administration 
(FDA) in September of 2006 for the treatment of EGFR-expressing colorectal cancers 
with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-
containing chemotherapy regimens.   
 
Thus, given these known facts, we hypothesize that the addition of panitumumab to 
CAPOX chemotherapy in KRAS wild-type patients will result in improved anti-cancer 
activity and improved outcomes for patients with unresectable or metastatic  
adenocarcinoma of the small bowel and ampulla of Vater.  We now propose a study to 
test this hypothesis by evaluating the addition of panitumumab to the standard of care 
chemotherapy treatment, CAPOX, for locally advanced or metastatic Small bowel 
adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). 
 


2009-0458
December 16, 2014
Abstract - Page 3
Updated Background Data on Anti-EGFR Therapy Combined with Oxaliplatin and Rationale 
for Study Design Change as of October 1, 2012. 
 
Since the initiation of this study further results regarding the combination of oxaliplatin and 
capecitabine therapy and anti-EGFR therapy have been presented and published in both 
metastatic colorectal cancer and metastatic esophagogastric cancer.  The overall 
summation of this data is that anti-EGFR therapy when combined with capecitabine and 
oxaliplatin has not provided any added benefit.  Anti-EGFR in combination with other 
chemotherapy and as a single-agent has shown marked activity in colorectal cancer and 
thus it appears that an antagonistic interaction between oxaliplatin and capecitabine and 
anti-EGFR therapy may be occurring.  We are thus providing an amendment to alter this 
study in the interest of both the outcome for patients and patient safety.  As a single agent 
panitumumab continues to represent a scientifically sound and interesting anti-cancer agent 
to explore in small bowel adenocarcinoma and ampullary adenocarcinoma, and thus this 
study will no longer explore combination therapy but will explore panitumumab as a single-
agent in refractory disease. 
Eligibility: (List All Criteria)
Inclusion:
1)
Patients must have histologically confirmed adenocarcinoma of the small bowel or ampulla of Vater 
that is either unresectable or metastatic.
2)
Adequate tumor tissue available for KRAS mutational analysis or known KRAS wild-type status.
3)
Prior progression on or intolerance to treatment with a fluoropyrimidine and oxaliplatin. Recurrence 
of disease within 6 months from the completion of adjuvant therapy with both a fluoropyrimidine and 
oxaliplatin is considered progression.
4)
Patients must have measurable disease as per the revised Response Evaluation Criteria In Solid 
Tumors (RECIST) criteria (Version 1.1).
5)
If radiation was previously received, the measurable disease must be outside the previous radiation 
field, unless this area has demonstrated evidence of radiographic growth.
6)
A minimum of 2 weeks must have elapsed from completion of any prior chemotherapy or 
radiotherapy or surgery and the start date of study therapy.
7)
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.
8)
Adequate organ function including: a) Absolute neutrophil count (ANC) =/>1,000/ul; b) Platelets 
=/>75,000/ul; c) Total bilirubin =/< 1.5 x ULN; in patients with known Gilbert’s syndrome direct bilirubin 
=/<1.5 x ULN will be used as organ function criteria, instead of total bilirubin; d) AST (SGOT)/ALT (SGPT) 
< 3 x ULN; e) Creatinine <2 x ULN.
9)
Negative urine or serum pregnancy test in women with childbearing potential (defined as not 
post-menopausal for 12 months or no previous surgical sterilization), within one week prior to initiation of 
treatment.
10)
The effects of panitumumab on the developing fetus are unknown. For this reason, women of 
childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of 


2009-0458
December 16, 2014
Abstract - Page 4
birth control) prior to study entry, for the duration of study participation, and for six months following the 
completion of therapy. Should a woman become pregnant while participating in this study, she should 
inform her treating physician immediately.
11)
Patients must sign an Informed Consent and Authorization indicating that they are aware of the 
investigational nature of this study and the known risks involved.
12)
Magnesium level =/> lower limit of normal.
Exclusion:
1)
Prior anti-epidermal growth factor receptor antibody therapy (eg. panitumumab or cetuximab) or 
prior small molecule anti-epidermal growth factor receptor therapy (eg. erlotinib) for adenocarcinoma of 
the small bowel or ampulla of Vater.
2)
Patients may not be receiving any other investigational agents nor have received any 
investigational drug 30 days prior to enrollment.
3)
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, 
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric 
illness/social situations that would limit adherence with study requirements.
4)
Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
5)
Because there is an unknown but potential risk for adverse events in nursing infants secondary to 
treatment of the mother with panitumumab, breast feeding must be discontinued.
6)
Age <18 years. Because no dosing or adverse event data are currently available on the use of 
panitumumab in patients <18 years of age, children are excluded from this study.
Is there an age limit?  Yes
Why?  Provide scientific justification:
18 years or older.  Because no dosing or adverse event data are currently available on the use of 
CAPOX and panitumumab in the pediatric age group.
Disease Group:
Gastrointestinal
Treatment Agents/Devices/Interventions:
Capecitabine, Oxaliplatin, Panitumumab
Proposed Treatment/Study Plan:
This is a single-center, open-label, single-arm phase II study.  Patients who enroll will 
have tumors tested for the presence of activating mutations in codons 12 or 13 , or at 
codon 61 (if tested) of the KRAS oncogene.  Only patients who have wild-type KRAS 
gene sequences at these codons will be eligible to undergo study treatment with 
panitumumab.
Panitumumab will be administered at 9 mg/kg given over approximately a 60-minute 


2009-0458
December 16, 2014
Abstract - Page 5
infusion through a peripheral or central catheter on Day 1 of a two-week cycle.  For 
doses >1000 mg the infusion time should be increased to 90 minutes. The panitumumab 
being administered in this study is not a commercially marketed product. Although it is 
expected to be very similar in safety and activity to the commercially marketed drug, it is 
possible that some differences may exist. Because this is not a commercially marketed 
drug, panitumumab can only be administered to patients enrolled in this clinical trial and 
may only be administered under the direction of physicians who are investigators in this 
clinical trial.
Study Calendar 
1
Informed consent must be obtained before any evaluations on this study to occur.
2.    Only patients who have wild-type KRAS gene sequences at codons 12 or 13, or at codon 61 if it is 
tested, will be eligible.  Testing may be performed at MD Anderson Cancer Center or an outside 
CLIA-certified laboratory.  For testing at MD Anderson Cancer Center five unstained slides or a paraffin 
embedded tumor block are required.    Tissue may be requested up to 6 weeks prior to first day of study 
treatment.  In consenting patients, additional archival tissue may be collected at the same time for use in 
future research.  Diagnostic imaging studies must be completed within 28 days prior to first day of study 
treatment. Hematologic, biochemistry, and serum pregnancy (if applicable) testing must be performed within 
7 days prior to first dose of study drug.  All other baseline evaluations must be completed within 10 days 
prior to first dose of study drug.  


2009-0458
December 16, 2014
Abstract - Page 6
3
For Cycle 1, baseline evaluations will suffice if performed within 7 days prior to first dose of study drug. 
4
Within 72 hours prior to start of the cycle (except for Cycle 1 as noted above).  
5
Patient will be instructed to report any adverse events to the research nurse at least once weekly (+/- 1 
day).  
6 
Imaging should be obtained every 4 cycles (+/- 1week allowance is made for scheduling).  . After a 
tumor evaluation is performed which demonstrates a tumor response (partial or complete), confirmation of 
the response may be obtained by a second evaluation to be performed 3 cycles later.  
7
For patients taken off study treatment for reasons other than progression, perform every 12 weeks (+/- 2 
week allowance is made for scheduling) after the End of Treatment Evaluation visit until documentation of 
progression if no other anti-cancer treatment is given.
8
CT scans or other imaging modality. MRI may be used in cases where it is felt to be unsafe to perform 
CT secondary to patient's history of dye allergy, or if the tumor is not adequately seen on CT for the 
purposes of this study.
9
Treatment-related adverse events occurring during study treatment or within 30 days after the last 
administration of study drug(s) will be followed until resolution or stabilization.  If the patient is unable or 
unwilling to return to M. D. Anderson for this assessment, the patient will be contacted by phone for this 
assessment.  
10
Every 3 months (+/- 2 weeks) from Post-Treatment Evaluation.
11
Hematology: hemoglobin, platelets, and absolute neutrophil count.  Chemistry:  creatinine, total bilirubin, 
AST, ALT, Magnesium, Potassium, Calcium.  In patients with known Gilbert’s syndrome direct bilirubin will 
also be performed
12 At time of or up to 10 days after decision to discontinue study treatment. 
13. Up to 35 days from last dose of study medication.
Statistical Considerations:
Study design and Sample Size: 
Amended Study Design, Sample Size, Efficacy and Toxicity Monitoring as of 
October 1, 2012: 


2009-0458
December 16, 2014
Abstract - Page 7
The primary endpoint of this phase II, single arm study is response rate (RR) for patients 
treated with single-agent Panitumumab. Patients will be evaluated for up to 8 cycles 
from their first dose, and a patient will be considered as a non-responder if no PR or CR 
has been documented after 8 cycles of treatment. Patients who withdraw early will be 
included in the ITT analysis. Based on our current data with a null hypothesis of </=1% 
RR to an inactive drug for refractory patients, a sample size of 17 patients with 
Panitumumab would be required to demonstrate a response rate of 17% using a 
binomial one-sample test with a two-sided alpha of 0.05 and power of 90%. 
 
The primary adverse event to be monitored will be the toxicity rate.  Toxicities to be 
included in toxicity monitoring include definite or probably treatment-related grade 3 or 4 
non-hematological toxicities, excluding grade 3 rash and grade 3 hypomagnesemia, 
which are both expected and manageable toxicities. Only toxicities during the first 4 
cycles of therapy will be used in toxicity monitoring. Accrual is estimated at 1 to 2 
patients per month.   
 
Sample Size and Endpoint Monitoring 
 
Response and toxicity will be monitored simultaneously using the Bayesian approach of 
Thall, Simon, Estey (1995, 1996) and the extension by Thall and Sung (1998). Data from 
a previous study of single agent Panitumumabe in Kras wildtype colorectal cancer 
demonstrated a response rate for Panitumumab is approximately 17%. The toxicity rate 
of Panitumumab will estimate it will be approximately 25%.  For the prior distribution of 
standard Panitumumab, we assumed a simple Dirichlet distribution and independence 
between OR and toxicity in 124 patients.  The parameters for this prior distribution are as 
follows:   
 
Dirichlet parameters for the joint prior distribution of objective response and 
toxicity rate assuming information on 124 patients and independence among 
response and toxicity for Panitumumab. 
 
 
 
 
 
 
No Response   
Response 
 
 
No Toxicity 
 
 
          77 
 
     16 
 
 
Toxicity 
 
 
          26 
 
       5 
 
A flat Dirichlet prior distribution for experimental Panitumumab was chosen reflective of 
information from the equivalent of 4 patients with the same marginal distributions as for 
Panitumumab (e.g., RR rate of 17% and toxicity rate of 25%). 
 
This regimen of Panitumumab will be considered worthy of further investigation if it elicits 
an increase in RR to 25% with acceptable toxicity.  A 25% toxicity rate is considered 
unacceptable.  Thus, interim monitoring rules, assuming the prior distributions above, 
were constructed that meet the following two conditions, 
1) 
Pr(ØS, Toxicity <ØE, Toxicity | data) > 0.95 and, 
2) 
Pr(ØS, Response <ØE, Response | data) < 0.05 
Where Ø E, Toxicity and ØE, Response are the true toxicity and response rates for Panitumumab, 
respectively.  The first rule provides for stopping the study if excessive toxicity is highly 
probable (i.e., probability >95%) for Panitumumab.  The second condition will stop the 
study early if the data suggest that it is unlikely (i.e., probability < 5%) that response rate 


2009-0458
December 16, 2014
Abstract - Page 8
of the drug is 17%. Assuming the minimum number of patients is 1, the maximum 
number of patients is 17 and the cohort size is 1.
The monitoring rule for the toxicity rate, based on these assumptions and monitoring 
conditions above is found in the following table.  For example, accrual will cease if 4 or 
more patients experience toxicities among the first 5 patients treated or if 6 or more 
patients experience toxicities among the first 10 patients.
 
Stop accrual if the number of toxicities is equal to or greater than indicated 
(i.e., # toxicities) among the number of patients evaluated (i.e., # patients) 
# Toxicities 
3-4 
4-6 
5-9 
6-11 
17-14 
8-16 
# Patients 
3-4 
5-6 
7-9 
10-11 
12-14 
15-16 
 
Monitoring the response rate, based on the above assumptions and monitoring will begin 
after 1 patient is treated (on an intent-to-treat basis). Following this rule, the trial will be 
terminated if [# Response]/[# patients evaluated] =< 0/8.  For example, accrual will 
cease if 0 or fewer patients experience a response in the first 8 patients treated.
Multc Lean Desktop (version 2.0.0) was used to generate the toxicity and futility stopping 
boundaries and the OC table. In order to utilize the software for the design, a beta (21, 
103) prior was assumed for the historical control response rate and a beta (31, 93) prior 
was assumed for the historical control toxicity rate. 
The probability of stopping the study early if the true response rate of the Panitumumab 
was not better than 17% was 35%.  Probabilities of stopping early for high true toxicity 
rates (i.e., 37%) were 57% when the true RR rate was 17% and 48% when true RR was 
25%.
Operating characteristics for simultaneous monitoring response and toxicity rates for patients treated with 
Panitumumab. 
True 
RR 
True 
Toxicity 
Rate 
True Probability Vector 
(RR/TX, RR/NTX,  
NRR/TX, NRR/NTX) 
Probability of 
Stopping 
 
Average number of 
patients treated 
 
8% 
12% 
(0.010,0.070,0.110,0.810) 
0.5174 
12 
8% 
25% 
(0.020,0.060,0.230,0.690) 
0.5637 
12 
8% 
37% 
(0.030,0.050,0.340,0.580) 
0.6885 
10 
17% 
12% 
(0.020,0.150,0.099,0.730) 
0.2319 
15 
17% 
25% 
(0.042,0.127,0.207,0.622) 
0.3055 
14 
17% 
37% 
(0.062,0.107,0.307,0.523) 
0.5042 
12 
25% 
12% 
(0.030,0.220,0.090,0.660) 
0.1078 
16 
25% 
25% 
(0.062,0.187,0.187,0.562) 
0.1934 
15 
25% 
37% 
(0.092,0.157,0.277,0.472) 
0.4241 
13 
 
Where Will Participants Be Enrolled:


2009-0458
December 16, 2014
Abstract - Page 9
Only at MDACC
Is this an NCI-Cancer Therapy Evaluation Protocol (CTEP)?
No
Is this an NCI-Division of Cancer Prevention Protocol (DCP)?
No
Estimated Accrual:
Total Accrual at MDACC:
27
Estimated monthly accrual at MDACC:
1-2
Accrual Comments:
The total accrual for this study is 27. There are 10 patients already enrolled and 3 have been treated with 
combination therapy, and 17 patients are to be enrolled for the single agent treatment.
Do you expect your target population to include non-english 
speaking participants?
No
Location of Treatment:
This protocol is performed on an Outpatient basis.
Length of Stay: What is the length & frequency of hospitalization?
NA
Return Visits: How often must participants come to MDACC?
Every 2 weeks
Home Care: Specify what, if any, treatment may be given at home.
NA
Name of Person at MDACC Responsible for Data Management:  Mary E. Brimer
Prior protocol at M. D. Anderson:
Has the Principal Investigator ever had a clinical or behavioral protocol at MDACC that accrued patients?
Yes
Data Monitoring Committee:
Is treatment assignment randomized? No
Is this a blinded or double-blinded study? No
Does this protocol have a schedule for interim and final analysis?
Yes
Please describe:
Amended Study Design, Sample Size, Efficacy and Toxicity Monitoring as of October 1, 2012: 


2009-0458
December 16, 2014
Abstract - Page 10
Response and toxicity will be monitored simultaneously using the Bayesian approach of Thall, Simon, 
Estey (1995, 1996) and the extension by Thall and Sung (1998).  Bayesian interim futility and toxicity 
rules will be used. Complete details are included in the Statistical Considerations section. Data from a 
previous study of single agent Panitumumabe in Kras wildtype colorectal cancer demonstrated a 
response rate for Panitumumab is approximately 17%.  The toxicity rate of Panitumumab will estimate it 
will be approximately 25%.  For the prior distribution of standard Panitumumab, we assumed a simple 
Dirichlet distribution and independence between OR and toxicity in 124 patients.  The parameters for this 
prior distribution are as follows:
Dirichlet parameters for the joint prior distribution of objective response and toxicity rate assuming 
information on 124 patients and independence among response and toxicity for Panitumumab.
                                                       No Response                    Response
        No Toxicity                                            77                                  16
        Toxicity                                                  26                                    5
A flat Dirichlet prior distribution for experimental Panitumumab was chosen reflective of information from 
the equivalent of 4 patients with the same marginal distributions as for Panitumumab (e.g., RR rate of 
17% and toxicity rate of 25%).
This regimen of Panitumumab will be considered worthy of further investigation if it elicits an increase in 
RR to 25% with acceptable toxicity.  A 25% toxicity rate is considered unacceptable.  Thus, interim 
monitoring rules, assuming the prior distributions above, were constructed that meet the following two 
conditions,
1)
Pr(ØS, Toxicity < ØE, Toxicity | data) > 0.95 and,
2)
Pr(ØS, Response <ØE, Response | data) < 0.05
Where ØE, Toxicity and ØE, Response are the true toxicity and response rates for Panitumumab, 
respectively.  The first rule provides for stopping the study if excessive toxicity is highly probable (i.e., 
probability >95%) for Panitumumab.  The second condition will stop the study early if the data suggest 
that it is unlikely (i.e., probability < 5%) that response rate of the drug is 17%. Assuming the minimum 
number of patients is 1, the maximum number of patients is 17 and the cohort size is 1.
The monitoring rule for the toxicity rate, based on these assumptions and monitoring conditions above is 
found in the following table.  For example, accrual will cease if 4 or more patients experience toxicities 
among the first 5 patients treated or if 6 or more patients experience toxicities among the first 10 patients.
      Stop accrual if the number of toxicities is equal to or greater than indicated
      (i.e., # toxicities) among the number of patients evaluated (i.e., # patients)
      # Toxicities        3-4      4-6      5-9     6-11    17-14      8-16
      # Patients          3-4      5-6     7-9    10-11    12-14    15-16
Monitoring the response rate, based on the above assumptions and monitoring will begin after 1 patient is 
treated (on an intent-to-treat basis). Following this rule, the trial will be terminated if [# Response]/[# 
patients evaluated] =< 0/8.  For example, accrual will cease if 0 or fewer patients experience a response 
in the first 8 patients treated.
Radiation Safety:
Does this study involve the administration of radioisotopes or a radioisotope 
labeled agent?
No


2009-0458
December 16, 2014
Abstract - Page 11
Is the radioactive compound (or drug) FDA approved and/or commercially 
available?
No
Investigational New Drugs:
Does this protocol require an IND?
Yes
Please list the IND holder and provide the IND number:
IND Holder:
MDACC
IND Number:
109220
Investigational Device:
Is the Investigational Device approved by the FDA?
N/A
Is the Investigational Device being used in the manner approved by 
the FDA?
N/A
Has the Investigational Device been modified in a manner not 
approved by the FDA?
N/A
Name of Device:
NA
Manufacturer:
NA
What is the FDA Status of the Investigational Device?
Not Marketed.
Is the study being conducted under an Investigational Device Exemption (IDE)? No
IDE Holder:
NA
IDE Number: NA
Risk Assessment:
Please answer the following questions regarding the Investigational Device.
Intended as an implant?
No
Purported or represented to be for use supporting or sustaining human life?
No
For use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or otherwise preventing impairment of human health?
No
You may attach sponsor documentation of the risk assessment:
NA
Will participant be charged for the Investigational Device? No
Sponsorship and Support Information:
Does the Study have a Sponsor or Supporter?
Yes


2009-0458
December 16, 2014
Abstract - Page 12
Sponsor or Supporter:
Amgen
Type(s) of Support:
Funds
Agent
Monitored by Sponsor or Sponsor Represenative (CRO)?
No
Is this Protocol listed on any Federal Grant or Foundation Funding Application?No
Biosafety:
Does this study involve the use of Recombinant DNA Technology? 
No
Does this study involve the use of organisms that are infectious to humans? 
No
Does this study involve stem cells?
No
Technology Commercialization:
Does this study include any agents or devices manufactured or produced at 
MD Anderson Cancer Center?
No
Laboratory Tests:
Where will laboratory tests be performed on patient materials?  (Please select all that apply)
Division of Pathology & Laboratory Medicine CLIA Certified Laboratory
Manufacturing:
Will you manufacture in full or in part (split manufacturing) a drug or biological 
product at the M. D. Anderson Cancer Center for the proposed clinical study?
No