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

NCT ID: NCT00634751

Last Updated: 2019-11-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2010-07-31

Brief Summary

This study involves the use of oxaliplatin, capecitabine, and sorafenib which are all drugs approved by the Food and Drug Administration (FDA) for use in the treatment of different cancers. Their use in this exact combination is considered experimental for the treatment of pancreas and biliary tract; however the combination has been tested in a preliminary trial. We are also testing a survey designed. The purpose of this research study is to investigate the chemotherapy drug sorafenib in combination with oxaliplatin and capecitabine chemotherapies for the treatment of pancreas and biliary tract cancers.to help patients report their side effects from chemotherapy treatments.

Detailed Description

Primary Objectives

• To assess the overall safety of sorafenib when administered with "the 2DOC regimen" capecitabine and oxaliplatin in patients with advanced or metastatic pancreas or biliary tract cancers.
• To define the dose limiting toxicity and maximally tolerated dose of this combination.
• To assess the clinical response rate (stable, partial and complete responses) of the combination in patients with advanced or metastatic pancreas or biliary tract cancers.

Secondary Objectives

• To define the time to progression and overall survival for patients treated with this regimen.
• To evaluate the congruency of the Adverse Events Self-Report Survey in determining patient reported side effects of treatment

Conditions

Pancreatic Neoplasms; Bile Duct Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I: 200mg Sorafenib+2DOC

Cohort 1: 200mg Sorafenib+2DOC

Oxaliplatin + Oral Capecitabine + Sorafenib

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: 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.

Capecitabine

Intervention Type: DRUG

Each course of oral capecitabine administration will commence following administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses as above, commencing with each cycle of therapy. Because capecitabine is provided in fixed dose forms, rounding will be necessary. Rounding will be to the nearest 150 mg on a per dose basis.

Sorafenib

Intervention Type: DRUG

Cohort 1 will receive 200 mg of sorafenib orally twice daily, cohort 2 will receive 400 mg 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. Sorafenib should be taken without food (at least 1 hour before or 2 hours after eating).

Cohort I (Dose escalation phase) Agent Dose Route Day Cycle length

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.

Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length

Sorafenib 400 mg BID Oral Daily Every 28 days

Phase I: 400mg Sorafenib BID+2DOC

Cohort 2: 400mg Sorafenib+2DOC

Oxaliplatin + Oral Capecitabine + Sorafenib

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: 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.

Capecitabine

Intervention Type: DRUG

Each course of oral capecitabine administration will commence following administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses as above, commencing with each cycle of therapy. Because capecitabine is provided in fixed dose forms, rounding will be necessary. Rounding will be to the nearest 150 mg on a per dose basis.

Sorafenib

Intervention Type: DRUG

Cohort 1 will receive 200 mg of sorafenib orally twice daily, cohort 2 will receive 400 mg 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. Sorafenib should be taken without food (at least 1 hour before or 2 hours after eating).

Cohort I (Dose escalation phase) Agent Dose Route Day Cycle length

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.

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

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: 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.

Capecitabine

Intervention Type: DRUG

Each course of oral capecitabine administration will commence following administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses as above, commencing with each cycle of therapy. Because capecitabine is provided in fixed dose forms, rounding will be necessary. Rounding will be to the nearest 150 mg on a per dose basis.

Sorafenib

Intervention Type: DRUG

Cohort 1 will receive 200 mg of sorafenib orally twice daily, cohort 2 will receive 400 mg 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. Sorafenib should be taken without food (at least 1 hour before or 2 hours after eating).

Cohort I (Dose escalation phase) Agent Dose Route Day Cycle length

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.

Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length

Sorafenib 400 mg BID Oral Daily Every 28 days

Phase II: Biliary Tract Cancer

Oxaliplatin + Oral Capecitabine + Sorafeni

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: 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.

Capecitabine

Intervention Type: DRUG

Each course of oral capecitabine administration will commence following administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses as above, commencing with each cycle of therapy. Because capecitabine is provided in fixed dose forms, rounding will be necessary. Rounding will be to the nearest 150 mg on a per dose basis.

Sorafenib

Intervention Type: DRUG

Cohort 1 will receive 200 mg of sorafenib orally twice daily, cohort 2 will receive 400 mg 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. Sorafenib should be taken without food (at least 1 hour before or 2 hours after eating).

Cohort I (Dose escalation phase) Agent Dose Route Day Cycle length

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.

Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length

Sorafenib 400 mg BID Oral Daily Every 28 days

Interventions

Oxaliplatin

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.

Intervention Type: DRUG

Capecitabine

Each course of oral capecitabine administration will commence following administration of oxaliplatin. Capecitabine 2250 mg/m2 will be given every 8 hours for a total of 6 doses as above, commencing with each cycle of therapy. Because capecitabine is provided in fixed dose forms, rounding will be necessary. Rounding will be to the nearest 150 mg on a per dose basis.

Intervention Type: DRUG

Sorafenib

Cohort 1 will receive 200 mg of sorafenib orally twice daily, cohort 2 will receive 400 mg 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. Sorafenib should be taken without food (at least 1 hour before or 2 hours after eating).

Cohort I (Dose escalation phase) Agent Dose Route Day Cycle length

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.

Cohort II (Phase II studies at MTD) Agent Dose Route Day Cycle length

Sorafenib 400 mg BID Oral Daily Every 28 days

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Noelle K LoConte, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Related Links

https://cancer.wisc.edu/

University of Wisconsin Carbone Cancer Center

Other Identifiers

CO07204

Identifier Type: OTHER

Identifier Source: secondary_id

H-2007-0248

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2011-00475

Identifier Type: REGISTRY

Identifier Source: secondary_id

A534260

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH\MEDICINE\HEM-ONC

Identifier Type: OTHER

Identifier Source: secondary_id

2007-0248

Identifier Type: -

Identifier Source: org_study_id