CO07204-Phase I/II of Oxaliplatin, Capecitabine & Sorafen... | NCT00634751

NCT00634751

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description
CO07204	Other Identifier	University of Wisconsin Carbone Cancer Center
H-2007-0248	Other Identifier	Institutional Review Board
NCI-2011-00475	Registry Identifier	NCI Trial ID
A534260	Other Identifier	UW Madison
SMPH\MEDICINE\HEM-ONC	Other Identifier	UW Madison

Status Module

Name	Class
Bayer	INDUSTRY
Sanofi	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase I: 200mg Sorafenib+2DOC	Experimental	Cohort 1: 200mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib	Drug: Oxaliplatin Drug: Capecitabine Drug: Sorafenib
Phase I: 400mg Sorafenib BID+2DOC	Experimental	Cohort 2: 400mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib	Drug: Oxaliplatin Drug: Capecitabine Drug: Sorafenib
Phase II: Pancreatic Cancer	Experimental	Oxaliplatin + Oral Capecitabine + Sorafeni	Drug: Oxaliplatin Drug: Capecitabine Drug: Sorafenib
Phase II: Biliary Tract Cancer	Experimental	Oxaliplatin + Oral Capecitabine + Sorafeni	Drug: Oxaliplatin Drug: Capecitabine Drug: Sorafenib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Oxaliplatin	Drug	On days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Following the infusion of oxaliplatin, the infusion line should be flushed with Dextrose 5% in Water.

Measure	Description	Time Frame
Overall Response Rate	Response rate of participant to treatment	Up to 18 months

Measure	Description	Time Frame
Progression-free Survival (PFS)	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.	Up to 18 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients must have histologically or cytologically confirmed locally advanced inoperable or metastatic adenocarcinoma of the pancreas or biliary tract who have not previously received more than one systemic treatment for their disease.
Age at least 18 years old
ECOG performance status 0-2.
Patients must have adequate organ and marrow function as defined below:
WBC at least 3,000
ANC at least 1,500
PLT at least 100,000
total bilirubin must be less than 2.5 x institutional upper limit of norm
AST(SGOT)/ALT(SGPT) must be less than 5 X institutional upper limit of normal
creatinine clearance must be greater than 50 mL/min as calculated by the Cockroft-Gault formula
Patients with ≤ grade 2 (CTC 3.0) neuropathy.
At least one measurable lesion as defined by RECIST criteria
The effects of oxaliplatin, capecitabine and sorafenib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because DNA alkylating agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Because the risk of toxicity in nursing infants secondary to oxaliplatin treatment of the mother is unknown but may be harmful, breastfeeding should be discontinued if the mother is treated with oxaliplatin.
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

No concomitant radiation therapy, or other systemic cancer therapies.
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other toxicities.
History of allergy to platinum compounds, capecitabine, sorafenib or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy.
Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, thrombolic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months, symptomatic congestive heart failure, unstable angina pectoris within 3 months prior to entry study, myocardial infarction within 6 months prior to study entry, ongoing cardiac arrhythmia (excluding atrial fibrillation), uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg, despite optimal medical management), pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug, or any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug, serious non-healing wound, ulcer, or bone fracture, evidence or history of bleeding diathesis or coagulopathy.
Pregnant or nursing women are excluded from this study because oxaliplatin, capecitabine and sorafenib is a DNA alkylating agent with the potential for teratogenic or abortifacient effects. Female patients of reproductive potential must have a negative urine or serum pregnancy test within two weeks prior to enrolling.
Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
Because of drug interactions with sorafenib, use of St. John's Wort or rifampin (rifampicin) is contraindicated. Patients may discontinue the use of these drugs to become eligible for the study
Any condition that impairs patient's ability to swallow whole pills.
HIV-positive patients receiving anti-retroviral therapy (HAART) are excluded from the study because of possible pharmacokinetic interactions.
Second malignancy within the past 3 years (excluding nonmelanoma skin cancer and in situ cancers) that has not been treated with curative intent and is not currently without evidence of disease,
Patients with known gastrointestinal malabsorption syndromes are excluded as this concurrent illness will affect absorption of the oral medications.

Name	Affiliation	Role
Noelle K LoConte, M.D.	University of Wisconsin, Madison	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Wisconsin		Madison	Wisconsin	53792	United States

Label	URL
University of Wisconsin Carbone Cancer Center	View source

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	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
FG002	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.
FG003	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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Customized			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Response Rate

Response rate of participant to treatment

Posted

Number

participants

Up to 18 months

ID	Title	Description
OG000	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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Albumin, serum-low (hypoalbuminemia)	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment

ID	Term
D010190	Pancreatic Neoplasms
D001650	Bile Duct Neoplasms

ID	Term
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004701	Endocrine Gland Neoplasms

ID	Term
D056831	Coordination Complexes
D009930	Organic Chemicals
D003841	Deoxycytidine
D003562	Cytidine

ID	Term
D000077150	Oxaliplatin
D000069287	Capecitabine
D000077157	Sorafenib