Trial Outcomes & Findings for CO07204-Phase I/II of Oxaliplatin, Capecitabine & Sorafenib for Advanced Pancreatic & Biliary Carcinoma (NCT NCT00634751)

NCT ID: NCT00634751

Last Updated: 2019-11-26

Results Overview

Response rate of participant to treatment

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

48 participants

Primary outcome timeframe

Up to 18 months

Results posted on

2019-11-26

Participant Flow

This study accrued through the Wisconsin Oncology Network (WON), a network of academic and private practice institutions across the state of Wisconsin and the upper Midwest.

Participant milestones

Participant milestones
Measure	Phase I: 200mg Sorafenib+2DOC Cohort 1: 200mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200 mg of sorafenib orally twice daily, beginning on the first day of the first cycle. If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort I Sorafenib 200 mg BID Oral Daily Every 28 days If 1/3 patients develop a DLT, enroll 3 patients at dose level -1 Sorafenib 200 mg po qd.	Phase I: 400mg Sorafenib BID+2DOC Cohort 2: 400mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length Sorafenib 400 mg BID Oral Daily Every 28 days	Phase II: Pancreatic Cancer Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily.	Phase II: Biliary Tract Cancer Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily.
Phase I: 200mg Sorafenib+2DOC STARTED	9	0	0	0
Phase I: 200mg Sorafenib+2DOC COMPLETED	8	0	0	0
Phase I: 200mg Sorafenib+2DOC NOT COMPLETED	1	0	0	0
Phase I: 400mg Sorafenib BID+2DOC STARTED	0	7	0	0
Phase I: 400mg Sorafenib BID+2DOC COMPLETED	0	6	0	0
Phase I: 400mg Sorafenib BID+2DOC NOT COMPLETED	0	1	0	0
Pancreatic and Bilial Tract Cancer STARTED	0	0	24	8
Pancreatic and Bilial Tract Cancer COMPLETED	0	0	23	7
Pancreatic and Bilial Tract Cancer NOT COMPLETED	0	0	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I: 200mg Sorafenib+2DOC Cohort 1: 200mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200 mg of sorafenib orally twice daily, beginning on the first day of the first cycle. If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort I Sorafenib 200 mg BID Oral Daily Every 28 days If 1/3 patients develop a DLT, enroll 3 patients at dose level -1 Sorafenib 200 mg po qd.	Phase I: 400mg Sorafenib BID+2DOC Cohort 2: 400mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length Sorafenib 400 mg BID Oral Daily Every 28 days	Phase II: Pancreatic Cancer Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily.	Phase II: Biliary Tract Cancer Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily.
Phase I: 200mg Sorafenib+2DOC Death	1	0	0	0
Phase I: 400mg Sorafenib BID+2DOC Death	0	1	0	0
Pancreatic and Bilial Tract Cancer Death	0	0	1	1

Baseline Characteristics

CO07204-Phase I/II of Oxaliplatin, Capecitabine & Sorafenib for Advanced Pancreatic & Biliary Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: 200mg Sorafenib+2DOC n=9 Participants Cohort 1: 200mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200 mg of sorafenib orally twice daily, beginning on the first day of the first cycle. If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort I Sorafenib 200 mg BID Oral Daily Every 28 days If 1/3 patients develop a DLT, enroll 3 patients at dose level -1 Sorafenib 200 mg po qd.	Phase I: 400mg Sorafenib BID+2DOC n=7 Participants Cohort 2: 400mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length Sorafenib 400 mg BID Oral Daily Every 28 days	Phase II: Pancreatic Cancer n=24 Participants Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily.	Phase II: Biliary Tract Cancer n=8 Participants Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily.	Total n=48 Participants Total of all reporting groups
Age, Customized =< 50 years of age	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Age, Customized 50-59 years of age	1 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants	2 Participants n=4 Participants	13 Participants n=21 Participants
Age, Customized 60-69 years of age	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	2 Participants n=4 Participants	16 Participants n=21 Participants
Age, Customized 70-79 years of age	3 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants	2 Participants n=4 Participants	12 Participants n=21 Participants
Age, Customized >= 80 years of age	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants	3 Participants n=4 Participants	22 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants	5 Participants n=4 Participants	26 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	7 Participants n=7 Participants	21 Participants n=5 Participants	5 Participants n=4 Participants	41 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	6 Participants n=7 Participants	24 Participants n=5 Participants	7 Participants n=4 Participants	46 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	9 participants n=5 Participants	7 participants n=7 Participants	24 participants n=5 Participants	8 participants n=4 Participants	48 participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 18 months

Response rate of participant to treatment

Outcome measures

Outcome measures
Measure	Phase I: 200mg Sorafenib+2DOC n=7 Participants Cohort 1: 200mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200 mg of sorafenib orally twice daily, beginning on the first day of the first cycle. If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort I Sorafenib 200 mg BID Oral Daily Every 28 days If 1/3 patients develop a DLT, enroll 3 patients at dose level -1 Sorafenib 200 mg po qd.	Phase I: 400mg Sorafenib BID+2DOC n=3 Participants Cohort 2: 400mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length Sorafenib 400 mg BID Oral Daily Every 28 days	Phase II: Pancreatic Cancer n=20 Participants Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200mg of sorafenib orally twice daily, both beginning on the first day of the first cycle.	Phase II: Biliary Tract Cancer n=7 Participants Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200mg of sorafenib orally twice daily, both beginning on the first day of the first cycle.
Overall Response Rate Partial Response	1 participants	1 participants	3 participants	1 participants
Overall Response Rate Stable Disease	5 participants	2 participants	11 participants	5 participants
Overall Response Rate Progressive Disease	1 participants	0 participants	6 participants	1 participants

SECONDARY outcome

Timeframe: Up to 18 months

Population: PFS was not a pre-specified Phase I outcome, and no data was collected or analyzed. No data was collected for Phase II biliary tract participants.

Time to progression, defined as number of days from day of first study drug administration to the day the patient experiences an event of disease progression or death; summarized using point estimates of the median time to progression and associated 95% confidence intervals for each stratum separately.

Outcome measures

Outcome measures
Measure	Phase I: 200mg Sorafenib+2DOC Cohort 1: 200mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200 mg of sorafenib orally twice daily, beginning on the first day of the first cycle. If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort I Sorafenib 200 mg BID Oral Daily Every 28 days If 1/3 patients develop a DLT, enroll 3 patients at dose level -1 Sorafenib 200 mg po qd.	Phase I: 400mg Sorafenib BID+2DOC Cohort 2: 400mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length Sorafenib 400 mg BID Oral Daily Every 28 days	Phase II: Pancreatic Cancer n=19 Participants Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200mg of sorafenib orally twice daily, both beginning on the first day of the first cycle.	Phase II: Biliary Tract Cancer Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200mg of sorafenib orally twice daily, both beginning on the first day of the first cycle.
Progression-free Survival (PFS)	—	—	6.0 Months Interval 2.5 to 9.6	—

SECONDARY outcome

Timeframe: Up to 18 months

Population: Overall survival was not a pre-specified Phase I outcome, and no data was collected or analyzed. No data was collected for Phase II biliary tract participants.

Overall survival, defined as number of days from the day of first study drug administration to the day the patient dies, summarized using point estimates of the median time to progression, and associated 95% confidence intervals

Outcome measures

Outcome measures
Measure	Phase I: 200mg Sorafenib+2DOC Cohort 1: 200mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200 mg of sorafenib orally twice daily, beginning on the first day of the first cycle. If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort I Sorafenib 200 mg BID Oral Daily Every 28 days If 1/3 patients develop a DLT, enroll 3 patients at dose level -1 Sorafenib 200 mg po qd.	Phase I: 400mg Sorafenib BID+2DOC Cohort 2: 400mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length Sorafenib 400 mg BID Oral Daily Every 28 days	Phase II: Pancreatic Cancer n=19 Participants Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200mg of sorafenib orally twice daily, both beginning on the first day of the first cycle.	Phase II: Biliary Tract Cancer Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200mg of sorafenib orally twice daily, both beginning on the first day of the first cycle.
Overall Survival	—	—	8.1 Months Interval 3.5 to 10.9	—

Adverse Events

Phase I: 200mg Sorafenib+2DOC

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Phase I: 400mg Sorafenib BID+2DOC

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Phase II: Pancreatic Cancer

Serious events: 14 serious events

Other events: 24 other events

Deaths: 0 deaths

Phase II: Biliary Tract Cancer

Serious events: 7 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Noelle LoConte

University of Wisconsin Carbone Cancer Center

Phone: 608-265-5883

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase I: 200mg Sorafenib+2DOC n=9 participants at risk Cohort 1: 200mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200 mg of sorafenib orally twice daily, beginning on the first day of the first cycle. If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort I Sorafenib 200 mg BID Oral Daily Every 28 days If 1/3 patients develop a DLT, enroll 3 patients at dose level -1 Sorafenib 200 mg po qd.	Phase I: 400mg Sorafenib BID+2DOC n=7 participants at risk Cohort 2: 400mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 400 mg of sorafenib orally twice daily, both beginning on the first day of the first cycle (see section 9.1). If needed, cohort -1 will be used, at 200 mg of sorafenib once daily. Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length Sorafenib 400 mg BID Oral Daily Every 28 days	Phase II: Pancreatic Cancer n=24 participants at risk Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200mg of sorafenib orally twice daily, both beginning on the first day of the first cycle.	Phase II: Biliary Tract Cancer n=8 participants at risk Oxaliplatin + Oral Capecitabine + Sorafeni Oxaliplatin: Days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Next, the infusion line should be flushed with Dextrose 5% in Water. Capecitabine: Oral capecitabine administration will start after administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses, commencing with each cycle of therapy. Capecitabine is provided in fixed dose forms, and rounding will be to the nearest 150 mg on a per dose basis. Sorafenib: 200mg of sorafenib orally twice daily, both beginning on the first day of the first cycle.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Metabolism and nutrition disorders Alkaline phosphatase	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Immune system disorders Allergic reaction/hypersensitivity	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Anorexia	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Metabolism and nutrition disorders AST, SGOT (serum glutamic oxaloacetic transaminase)	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Nervous system disorders Confusion	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Death	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	14.3% 1/7 • Adverse event data were collected for 2 years and 5 months.	20.8% 5/24 • Adverse event data were collected for 2 years and 5 months.	25.0% 2/8 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Dehydration	22.2% 2/9 • Number of events 2 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	12.5% 1/8 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Diarrhea	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	14.3% 1/7 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Distension/bloating	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	22.2% 2/9 • Number of events 2 • Adverse event data were collected for 2 years and 5 months.	14.3% 1/7 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Blood and lymphatic system disorders Edema	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
General disorders Fatigue	11.1% 1/9 • Number of events 2 • Adverse event data were collected for 2 years and 5 months.	14.3% 1/7 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Blood and lymphatic system disorders Hemoglobin	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	8.3% 2/24 • Number of events 2 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Blood and lymphatic system disorders Hemorrhage	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	8.3% 2/24 • Number of events 2 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Cardiac disorders Hypotension	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	14.3% 1/7 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	12.5% 1/8 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	14.3% 1/7 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Ileus	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	8.3% 2/24 • Number of events 2 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Infections and infestations Infection	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	14.3% 1/7 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	25.0% 2/8 • Number of events 2 • Adverse event data were collected for 2 years and 5 months.
Investigations INR (International Normalized Ratio of Prothrombin Time)	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Surgical and medical procedures Intra-operative injury	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Hepatobiliary disorders Liver dysfunction/failure	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Mucositis/stomatitis	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Musculoskeletal and connective tissue disorders Muscle weakness	11.1% 1/9 • Number of events 2 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Nausea	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	12.5% 1/8 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	22.2% 2/9 • Number of events 3 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	12.5% 1/8 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Obstruction	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	12.5% 1/8 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.
General disorders Pain	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	14.3% 1/7 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	25.0% 6/24 • Number of events 6 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Perforation	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	12.5% 1/8 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.
Blood and lymphatic system disorders Platelets	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia)	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Skin and subcutaneous tissue disorders Rash	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Renal and urinary disorders Renal failure	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	12.5% 1/8 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.
General disorders Rigors/chills	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Nervous system disorders Somnolence/depressed level of consciousness	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/24 • Adverse event data were collected for 2 years and 5 months.	12.5% 1/8 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Stricture/stenosis	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Nervous system disorders Syncope	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/8 • Adverse event data were collected for 2 years and 5 months.
Vascular disorders Thrombosis	11.1% 1/9 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	0.00% 0/7 • Adverse event data were collected for 2 years and 5 months.	12.5% 3/24 • Number of events 3 • Adverse event data were collected for 2 years and 5 months.	12.5% 1/8 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.
Gastrointestinal disorders Vomiting	0.00% 0/9 • Adverse event data were collected for 2 years and 5 months.	14.3% 1/7 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	4.2% 1/24 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.	12.5% 1/8 • Number of events 1 • Adverse event data were collected for 2 years and 5 months.