Study of Gemcitabine/Taxotere/Xeloda (GTX) in Combination With Cisplatin and Irinotecan in Subjects With Metastatic Pancreatic Cancer

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT02324543
• Collaborator: Swim Across America Laboratory (Other)
• Enrollment: 47
• Location: 1
• Arms: 6
• Actual Duration (Months): 60
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This study will be looking at whether gemcitabine, taxotere, and xeloda (GTX) in combination with cisplatin and irinotecan is effective (anti-tumor activity) and safe in patients with metastatic pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Adenocarcinoma	Drug: Gemcitabine; Drug: Taxotere; Drug: Xeloda; Drug: Cisplatin; Drug: Irinotecan	Phase 1/Phase 2

Detailed Description

The study is being done in 2 parts. The first part is the dose escalation (Phase I) part of the study where the dose of irinotecan is increased until the highest safe dose of irinotecan is defined that can be given with gemcitabine, taxotere, xeloda, and cisplatin.

After the safe dose of irinotecan in combination with gemcitabine, taxotere, xeloda, and cisplatin is defined, the second part of the study (Phase 2) will use these defined doses to look at how effective these drugs are against advanced pancreatic cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of Gemcitabine/Taxotere/Xeloda (GTX) in Combination With Cisplatin and Irinotecan in Subjects With Metastatic Pancreatic Cancer
• Actual Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Jun 1, 2019
• Actual Study Completion Date: Feb 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose level 1 - Phase 1 Gemcitabine - 400 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/twice daily (BID) Cisplatin - 15 mg/m^2 Irinotecan - 20 mg/m^2	Drug: Gemcitabine; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar ; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel ; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine ; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol ; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar
Experimental: Dose Level 2 - Phase 1 Gemcitabine - 400 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/BID Cisplatin - 15 mg/m^2 Irinotecan - 40 mg/m^2	Drug: Gemcitabine; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar ; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel ; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine ; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol ; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar
Experimental: Dose Level 3 - Phase 1 Gemcitabine - 400 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/BID Cisplatin - 15 mg/m^2 Irinotecan - 60 mg/m^2	Drug: Gemcitabine; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar ; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel ; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine ; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol ; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar
Experimental: Dose Level 1a - Phase 1 Gemcitabine - 500 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/BID Cisplatin - 20 mg/m^2 Irinotecan - 20 mg/m^2	Drug: Gemcitabine; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar ; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel ; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine ; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol ; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar
Experimental: Dose level 1b - Phase 1 Gemcitabine - 500 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/BID Cisplatin - 20 mg/m^2 Irinotecan - 40 mg/m^2	Drug: Gemcitabine; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar ; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel ; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine ; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol ; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar
Experimental: Phase 2 Gemcitabine - 500 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/BID Cisplatin - 20 mg/m^2 Irinotecan - 20 mg/m^2	Drug: Gemcitabine; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar ; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel ; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine ; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol ; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Gemcitabine [28 days]

   Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.

2. Maximum Tolerated Dose (MTD) of Docetaxel [28 days]

   Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.

3. Maximum Tolerated Dose (MTD) of Capecitabine [28 days]

   Dose escalation (phase I portion of the trial only) to determine the MTD in mg for twice daily (BID) use.

4. Maximum Tolerated Dose (MTD) of Cisplatin [28 days]

   Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.

5. Maximum Tolerated Dose (MTD) of Irinotecan [28 days]

   Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.

6. Overall Survival (OS) Rate at 9 Months [9 months]

   OS will be measured as the percentage of subjects alive at 9 months. (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve. (Phase 2 data only)

Secondary Outcome Measures

1. Response Rate (RR) Using RECIST 1.1 Criteria [43 months]

   RR is defined as the percentage of participants achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.

2. Disease Control Rate (DCR) Using RECIST 1.1 Criteria [43 months]

   DCR is defined as the percentage of participants achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.

3. Progression-free Survival (PFS) Using RECIST 1.1 Criteria [5 years]

   PFS is defined as the number of months from the date of first dose to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

4. Overall Survival (OS) [5 years]

   OS will be measured (in months) from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 76 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologically or cytologically confirmed untreated metastatic pancreatic adenocarcinoma.

2. Have measurable disease.

3. Male or non-pregnant and non-lactating female of age >18 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 . ECOG 0 indicates that the patient is fully active and able to carry on all pre-disease activities without restriction; and, ECOG 1 indicates that the patient is restricted in physically strenuous activity but is ambulatory and able to carry out work of a light or sedentary nature

5. Subjects must have adequate organ and marrow function.

6. Must use acceptable form of birth control prior to study and and for the duration of study.

7. Willing and able to comply with study procedures

Exclusion Criteria:

1. Patient who have had any prior chemotherapy within 5 years of enrollment.

2. Patient who have had radiotherapy for pancreatic cancer.

3. Age ≥ 76 years

4. Patient who is receiving or have received any other investigational agents within 28 days prior to Day 1 of treatment in this study.

5. Patient who has undergone major surgery, other than diagnostic surgery within 28 days prior to Day 1 of treatment in this study.

6. Patient who has known brain metastases.

7. Patient with history of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, taxotere, xeloda, cisplatin, or irinotecan.

8. Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

9. Patient who has serious medical risk factors involving any of the major organ systems.

10. Patient who has known history of infection with HIV, hepatitis B, or hepatitis C.

11. Pregnant or breast feeding.

12. Patient is unwilling or unable to comply with study procedures

13. Patient with clinically significant wound

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Swim Across America Laboratory

Investigators

• Principal Investigator: Dung Le, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 17, 2019

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02324543
• Other Study ID Numbers: J14161; J14161; IRB00053208
• First Posted: Dec 24, 2014
• Last Update Posted: Mar 2, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Gemcitabine; Docetaxel; Capecitabine; Irinotecan

Study Results

Participant Flow

Arm/Group Title	Dose Level 1- Phase 1	Dose Level 1a - Phase 1	Dose Level 1b - Phase 1	Dose Level 2 - Phase 1	Dose Level 3 - Phase 1	Phase 2
Arm/Group Description	Gemcitabine: 400 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 15 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Gemcitabine - 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda - 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan - 40 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Gemcitabine - 400 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda - 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin -15 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan - 40 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Gemcitabine - 400 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda - 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin - 15 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan - 60 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Period Title: Overall Study
STARTED	6	6	3	4	4	24
COMPLETED	6	6	3	4	4	24
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Dose Level 1 - Phase 1	Dose Level 1a - Phase 1	Dose Level 1b - Phase 1	Dose Level 2 - Phase 1	Dose Level 3 - Phase 1	Phase 2	Total
Arm/Group Description	Gemcitabine: 400 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 15 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Gemcitabine - 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda - 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan - 40 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Gemcitabine - 400 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda - 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin -15 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan - 40 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Gemcitabine - 400 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda - 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin - 15 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan - 60 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle	Total of all reporting groups
Overall Participants	6	6	3	4	4	24	47
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 50%	2 33.3%	2 66.7%	4 100%	2 50%	13 54.2%	26 55.3%
>=65 years	3 50%	4 66.7%	1 33.3%	0 0%	2 50%	11 45.8%	21 44.7%
Sex: Female, Male (Count of Participants)
Female	4 66.7%	3 50%	1 33.3%	1 25%	3 75%	8 33.3%	20 42.6%
Male	2 33.3%	3 50%	2 66.7%	3 75%	1 25%	16 66.7%	27 57.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	1 4.2%	1 2.1%
Not Hispanic or Latino	6 100%	6 100%	3 100%	4 100%	4 100%	23 95.8%	46 97.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 16.7%	0 0%	1 25%	0 0%	0 0%	2 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 16.7%	0 0%	1 25%	1 25%	2 8.3%	5 10.6%
White	6 100%	4 66.7%	3 100%	2 50%	3 75%	22 91.7%	40 85.1%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Gemcitabine
Description	Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1
Arm/Group Description	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Measure Participants	23
Number [mg/m^2]	500

2. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Docetaxel
Description	Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1
Arm/Group Description	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Measure Participants	23
Number [mg/m^2]	20

3. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Capecitabine
Description	Dose escalation (phase I portion of the trial only) to determine the MTD in mg for twice daily (BID) use.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1
Arm/Group Description	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Measure Participants	23
Number [mg]	500

4. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Cisplatin
Description	Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1
Arm/Group Description	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Measure Participants	23
Number [mg/m^2]	20

5. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Irinotecan
Description	Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1
Arm/Group Description	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Measure Participants	23
Number [mg/m^2]	20

6. Primary Outcome

Title	Overall Survival (OS) Rate at 9 Months
Description	OS will be measured as the percentage of subjects alive at 9 months. (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve. (Phase 2 data only)
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

This measure was only assessed for Phase 2. Per protocol, the 6 subjects treated at the MTD (DL1a) during dose escalation (Phase 1) were counted toward the total sample size of 30 subjects for the Phase 2 outcome measure.

Arm/Group Title	Phase 2
Arm/Group Description	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Measure Participants	30
Number (95% Confidence Interval) [percentage of participants]	57 950%

7. Secondary Outcome

Title	Response Rate (RR) Using RECIST 1.1 Criteria
Description	RR is defined as the percentage of participants achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Time Frame	43 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2
Arm/Group Description	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Measure Participants	30
Number (95% Confidence Interval) [percentage of participants]	57 950%

8. Secondary Outcome

Title	Disease Control Rate (DCR) Using RECIST 1.1 Criteria
Description	DCR is defined as the percentage of participants achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Time Frame	43 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2
Arm/Group Description	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Measure Participants	30
Number (95% Confidence Interval) [percentage of participants]	87 1450%

9. Secondary Outcome

Title	Progression-free Survival (PFS) Using RECIST 1.1 Criteria
Description	PFS is defined as the number of months from the date of first dose to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2
Arm/Group Description	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Measure Participants	30
Median (95% Confidence Interval) [Months]	8.34

10. Secondary Outcome

Title	Overall Survival (OS)
Description	OS will be measured (in months) from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2
Arm/Group Description	Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
Measure Participants	30
Median (95% Confidence Interval) [Months]	11.02

Adverse Events

Time Frame	All adverse events will be collected from the first dose up to 30 days after last dose.
Arm/Group Title	Dose Level 1 - Phase 1		Dose Level 1a - Phase 1		Dose Level 1b - Phase 1		Dose Level 2 - Phase 1		Dose Level 3 - Phase 1		Phase 2
Arm/Group Description	Gemcitabine: 400 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 15 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle		Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle		Gemcitabine - 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda - 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan - 40 mg/m^2 IV on days 4 and 11 of a 21 day cycle		Gemcitabine - 400 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda - 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin -15 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan - 40 mg/m^2 IV on days 4 and 11 of a 21 day cycle		Gemcitabine - 400 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere - 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda - 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin - 15 mg/m^2 IV on days 4 and 11 of a 21 day cycle Irinotecan - 60 mg/m^2 IV on days 4 and 11 of a 21 day cycle		Gemcitabine: 500 mg/m^2 IV on days 4 and 11 of a 21 day cycle Taxotere: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle Xeloda: 500 mg/BID twice a day orally on days 1-14 of a 21 day cycle Cisplatin: 20 mg/m^2 IV on Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2 IV on days 4 and 11 of a 21 day cycle
All Cause Mortality
	Dose Level 1 - Phase 1		Dose Level 1a - Phase 1		Dose Level 1b - Phase 1		Dose Level 2 - Phase 1		Dose Level 3 - Phase 1		Phase 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/24 (0%)
Serious Adverse Events
	Dose Level 1 - Phase 1		Dose Level 1a - Phase 1		Dose Level 1b - Phase 1		Dose Level 2 - Phase 1		Dose Level 3 - Phase 1		Phase 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/6 (16.7%)		1/3 (33.3%)		2/4 (50%)		1/4 (25%)		2/24 (8.3%)
Blood and lymphatic system disorders
Febrile neutropenia	0/6 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	0/4 (0%)	0	1/4 (25%)	1	1/24 (4.2%)	1
Metabolism and nutrition disorders
Hypokalemia	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/24 (4.2%)	1
Nervous system disorders
Leukoencephalopathy	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	0/4 (0%)	0	0/24 (0%)	0
Renal and urinary disorders
Acute Renal Failure	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	0/4 (0%)	0	0/24 (0%)	0
Other (Not Including Serious) Adverse Events
	Dose Level 1 - Phase 1		Dose Level 1a - Phase 1		Dose Level 1b - Phase 1		Dose Level 2 - Phase 1		Dose Level 3 - Phase 1		Phase 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		6/6 (100%)		3/3 (100%)		4/4 (100%)		4/4 (100%)		24/24 (100%)
Blood and lymphatic system disorders
Anemia	4/6 (66.7%)	4	4/6 (66.7%)	4	2/3 (66.7%)	2	1/4 (25%)	1	2/4 (50%)	2	14/24 (58.3%)	14
Febrile neutropenia	0/6 (0%)	0	1/6 (16.7%)	1	2/3 (66.7%)	2	0/4 (0%)	0	1/4 (25%)	1	1/24 (4.2%)	1
Eye disorders
Blurred vision	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/24 (4.2%)	1
Gastrointestinal disorders
Anorexia	1/6 (16.7%)	1	2/6 (33.3%)	2	1/3 (33.3%)	1	1/4 (25%)	1	0/4 (0%)	0	6/24 (25%)	6
Abdominal Pain	2/6 (33.3%)	2	1/6 (16.7%)	1	0/3 (0%)	0	1/4 (25%)	1	2/4 (50%)	2	3/24 (12.5%)	3
Diarrhea	5/6 (83.3%)	5	3/6 (50%)	3	3/3 (100%)	3	3/4 (75%)	3	4/4 (100%)	4	17/24 (70.8%)	17
Dry Mouth	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	3/24 (12.5%)	3
Flatulence	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	5/24 (20.8%)	5
Gastroesophageal reflux disease	0/6 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	3/24 (12.5%)	3
Mucositis oral	1/6 (16.7%)	1	2/6 (33.3%)	2	2/3 (66.7%)	2	0/4 (0%)	0	0/4 (0%)	0	6/24 (25%)	6
Nausea	3/6 (50%)	3	2/6 (33.3%)	2	2/3 (66.7%)	2	2/4 (50%)	2	2/4 (50%)	2	12/24 (50%)	12
Vomiting	3/6 (50%)	3	4/6 (66.7%)	4	1/3 (33.3%)	1	2/4 (50%)	2	2/4 (50%)	2	9/24 (37.5%)	9
Abdominal distension	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Colitis	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Rectal Pain	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Bloating	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/24 (4.2%)	1
Early satiety	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	2/24 (8.3%)	2
Constipation	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Tooth sensitivity	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
General disorders
Edema	1/6 (16.7%)	1	3/6 (50%)	3	2/3 (66.7%)	2	0/4 (0%)	0	1/4 (25%)	1	4/24 (16.7%)	4
Fatigue	3/6 (50%)	3	0/6 (0%)	0	1/3 (33.3%)	1	2/4 (50%)	2	3/4 (75%)	3	16/24 (66.7%)	16
Fever	0/6 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	5/24 (20.8%)	5
Sweating	1/6 (16.7%)	1	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	1/24 (4.2%)	1
Cold Intolerance	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Infections and infestations
Thrush	0/6 (0%)	0	2/6 (33.3%)	2	0/3 (0%)	0	1/4 (25%)	1	0/4 (0%)	0	1/24 (4.2%)	1
Injury, poisoning and procedural complications
Bruising	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	0/24 (0%)	0
Investigations
Alanine aminotransferase increased	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/4 (25%)	1	0/4 (0%)	0	3/24 (12.5%)	3
Creatinine, increased	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	4/24 (16.7%)	4
Lymphocyte count decreased	2/6 (33.3%)	2	3/6 (50%)	3	2/3 (66.7%)	2	1/4 (25%)	1	0/4 (0%)	0	9/24 (37.5%)	9
Neutrophil count decreased	3/6 (50%)	3	3/6 (50%)	3	2/3 (66.7%)	2	0/4 (0%)	0	3/4 (75%)	3	15/24 (62.5%)	15
Platelet count decreased	3/6 (50%)	3	2/6 (33.3%)	2	2/3 (66.7%)	2	1/4 (25%)	1	1/4 (25%)	1	9/24 (37.5%)	9
Weight Loss	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	0/4 (0%)	0	3/24 (12.5%)	3
White blood count decreased	2/6 (33.3%)	2	2/6 (33.3%)	2	2/3 (66.7%)	2	0/4 (0%)	0	3/4 (75%)	3	12/24 (50%)	12
Aspartate aminotransferase increased	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	0/4 (0%)	0	0/24 (0%)	0
Weight gain	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/6 (16.7%)	1	2/6 (33.3%)	2	1/3 (33.3%)	1	0/4 (0%)	0	4/4 (100%)	4	3/24 (12.5%)	3
Hypocalcemia	0/6 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	2/24 (8.3%)	2
Hypokalemia	1/6 (16.7%)	1	1/6 (16.7%)	1	1/3 (33.3%)	1	2/4 (50%)	2	1/4 (25%)	1	6/24 (25%)	6
Hypomagnesemia	1/6 (16.7%)	1	4/6 (66.7%)	4	3/3 (100%)	3	2/4 (50%)	2	3/4 (75%)	3	15/24 (62.5%)	15
Hypophosphatemia	1/6 (16.7%)	1	1/6 (16.7%)	1	2/3 (66.7%)	2	1/4 (25%)	1	0/4 (0%)	0	4/24 (16.7%)	4
Hyponatremia	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	1/24 (4.2%)	1
Musculoskeletal and connective tissue disorders
Back Pain	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	2/24 (8.3%)	2
Generalized muscle weakness	1/6 (16.7%)	1	0/6 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	1/4 (25%)	1	3/24 (12.5%)	3
Arthralgia	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Muscle cramps	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	2/24 (8.3%)	2
Nervous system disorders
Dizziness	0/6 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	0/4 (0%)	0	2/4 (50%)	2	4/24 (16.7%)	4
Dysgeusia	1/6 (16.7%)	1	2/6 (33.3%)	2	2/3 (66.7%)	2	2/4 (50%)	2	1/4 (25%)	1	17/24 (70.8%)	17
Neuropathy	3/6 (50%)	3	3/6 (50%)	3	3/3 (100%)	3	1/4 (25%)	1	1/4 (25%)	1	15/24 (62.5%)	15
Headache	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	1/24 (4.2%)	1
Leukoencephalopathy	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	0/4 (0%)	0	0/24 (0%)	0
Memory impairment	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Psychiatric disorders
Confusion	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Insomnia	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Depression	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Renal and urinary disorders
Chronic kidney disease	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	3/24 (12.5%)	3
Acute renal failure	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	0/4 (0%)	0	0/24 (0%)	0
Nocturia	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/6 (16.7%)	1	1/6 (16.7%)	1	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	6/24 (25%)	6
Sore Throat	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/4 (0%)	0	3/24 (12.5%)	3
Hiccups	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Cough	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Dyspnea	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	5/6 (83.3%)	5	2/6 (33.3%)	2	1/3 (33.3%)	1	1/4 (25%)	1	3/4 (75%)	3	12/24 (50%)	12
Dry Skin	4/6 (66.7%)	4	1/6 (16.7%)	1	2/3 (66.7%)	2	0/4 (0%)	0	2/4 (50%)	2	1/24 (4.2%)	1
Erythema	1/6 (16.7%)	1	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	2/24 (8.3%)	2
Nail discoloration	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/4 (25%)	1	0/4 (0%)	0	1/24 (4.2%)	1
Palmar-plantar erythrodysesthesia	1/6 (16.7%)	1	2/6 (33.3%)	2	0/3 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	0/24 (0%)	0
Rash	0/6 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	1/4 (25%)	1	0/4 (0%)	0	7/24 (29.2%)	7
Skin hyperpigmentation	1/6 (16.7%)	1	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	2/24 (8.3%)	2
Nail changes	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	0/24 (0%)	0
Pruritis	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	0/24 (0%)	0
Skin ulceration	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/24 (4.2%)	1
Nail Loss	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/24 (4.2%)	1
Nail ridging	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Vascular disorders
Phlebitis	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	2/4 (50%)	2	0/4 (0%)	0	2/24 (8.3%)	2
Hypertension	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0
Hypotension	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	1/24 (4.2%)	1
Hot flashes	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/24 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.