Pilot Study of Sorafenib and Bi-weekly Capecitabine in Patients With Advanced Breast and Gastrointestinal Tumors

NCT01640665 | Completed Phase 1 DMC

• 1 other identifier: GC0212
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find the maximum tolerated dose of the combination of two drugs. The two drugs are Sorafenib and Capecitabine. The drug Sorafenib is an approved drug which is used to treat certain cancers. The drug Capecitabine is approved to treat patients with advanced breast cancer as well as early stage colon cancer.

Conditions

Metastatic Breast Cancer; Gastrointestinal Tumors

Keywords

histologically; unresectable; metastatic; Phase 1; Breast Cancer; GI Tumors; Sorafenib; Capecitabine

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose / Safety

  Primary Objectives: * Safety * Determination of maximum tolerated dose

  4 weeks

Secondary Outcomes (1)

• Response

  8 Weeks

Study Arms (1)

Sorafenib and Capecitabine

EXPERIMENTAL

One cycle will consist of 4 weeks of treatment. The dose of Sorafenib will be 600 mg administered orally daily in divided doses. Capecitabine will be given at a fixed dose of 2000 mg orally BID x 7 days every 14 days

Drug: Sorafenib; Drug: Capecitabine

Interventions

Sorafenib DRUG

One cycle will consist of 4 weeks of treatment. The dose of Sorafenib will be 600 mg administered orally daily in divided doses.

Also known as: Sorafenib (Nexavar)

Sorafenib and Capecitabine

Capecitabine DRUG

Capecitabine will be given at a fixed dose of 2000 mg orally BID x 7 days every 14 days.

Also known as: Capecitabine (Xeloda)

Sorafenib and Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Life expectancy of at least 12 weeks (3 months).
• ECOG Performance Status 0 or 1.
• Histologically confirmed unresectable or metastatic breast and/or GI tumors for which curative standard treatments are unavailable
• Adequate bone marrow, liver and renal function as assessed by the following:
• Hemoglobin \> 9.0 g/dl
• Absolute neutrophil count (ANC) \>1,500/mm3
• Platelet count \> 100,000/mm3
• Total bilirubin \< 1.5 times ULN
• ALT and AST \< 2.5 times the ULN ( \< 5 x ULN for patients with liver involvement)
• GFR \> 30 ml/min
• All acute toxic effects (excluding alopecia and neuropathy) of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF).
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test.
• Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
• Subject must be able to swallow and retain oral medication.

You may not qualify if:

• Metastatic brain or meningeal tumors (unless subject completed definitive therapy more than 1 month previously and is stable off steroids).
• Uncontrolled hypertension defined as systolic blood pressure \> 140 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
• Active or clinically significant cardiac disease including:
• Congestive heart failure - New York Heart Association (NYHA) \> Class II.
• Active coronary artery disease.
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
• Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.
• Subject with any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 2 or higher within 4 weeks of study enrollment; any other hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 3 or higher within 4 weeks of study enrollment.
• Major surgery, open biopsy or significant traumatic injury within 30 days of first study drug.
• Presence of an active non-healing wound, non-healing ulcer, or bone fracture.
• Thrombotic or embolic events such as a cerebrovascular accident (including transient ischemic attacks) within 3 month of informed consent.
• Anticoagulation with warfarin is not permitted.
• Evidence or history of bleeding diathesis or coagulopathy.
• Subjects who have used strong CYP3A4 inducers (eg, phenytoin, carbamazepine, phenobarbital, St. John's Wort \[Hypericum perforatum\], dexamethasone at a dose of greater than 16 mg daily, or rifampin \[rifampicin\], and/or rifabutin) within 30 days of trial enrollment.
• Subjects with a history of dihydopyrimidine dehydrogenase (DHPD) deficiency or severe and unexpected reactions to fluropyrimidines.

Sponsors & Collaborators

• Yale University: lead
• Bayer: collaborator

Study Sites (1)

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

Related Links

• Yale Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms; Digestive System Neoplasms; Neoplasm Metastasis

Interventions

Sorafenib; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Digestive System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Gina Chung, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2012
• First Posted: July 16, 2012
• Study Start: July 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: September 16, 2016

Record last verified: 2016-09

Locations

US (1)