Study of the Pharmacokinetics/Safety of Sorafenib + Capecitabine in Advanced Solid Tumors

NCT00613145 | Completed Phase 1

• 1 other identifier: SCRI REFMAL 122
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, randomized, safety and pharmacokinetic (PK) study of sorafenib given in combination with capecitabine. The study will enroll two simultaneous cohorts; patients will be randomly assigned to either Cohort A or Cohort B. A third cohort (C) may be added to the protocol at a later date.

Conditions

Refractory Malignancy

Keywords

Refractory Malignancy; Phase I; Sorafenib; Capecitabine

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of the combination therapy

  18 Months

Secondary Outcomes (1)

• Evaluation of antitumor activity of the combination therapy

  18 months

Study Arms (2)

A

ACTIVE COMPARATOR

Treatment with Capecitabine and Sorafenib

Drug: Capecitabine and Sorafenib

B

ACTIVE COMPARATOR

Treatment with Capecitabine and Sorafenib

Drug: Capecitabine and Sorafenib

Interventions

Capecitabine and Sorafenib DRUG

During Cycle 1, patients will receive capecitabine alone for the first 7 days (Cohort A will receive 750 mg/m2 of capecitabine twice daily). For Days 8-14 of Cycle 1, patients will receive capecitabine (750 mg/m2 twice daily for Cohort A) combined with sorafenib (400 mg twice daily); on Days 15-21 of Cycle 1, patients will receive sorafenib alone (400 mg twice daily). Beginning with Day 1 of Cycle 2 and all treatment cycles thereafter, patients will be dosed as follows: Cohort A will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 750 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle.

Also known as: Xeloda, Nexavar

A

Eligibility Criteria

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

You may qualify if:

• Patients with advanced solid tumor malignancy for whom no effective therapy exists or who have failed effective therapy. Exceptions are patients with advanced solid malignancies where either capecitabine or sorafenib has been approved as initial chemotherapy either alone or in combination.
• A maximum of 4 prior cytotoxic chemotherapy regimens in the metastatic setting.
• Patients previously treated with capecitabine or infusional 5-FU are eligible, but must not have been a part of the immediately prior regimen, or received the treatment within 3 months prior to study initiation.
• Patients who have received prior radiation therapy are eligible, provided that this is not the only site of evaluable disease. Prior therapy must have been completed \> 3 weeks before study enrollment.
• An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.
• Life expectancy of \> 3 months.
• Adequate bone marrow, liver, and renal function as assessed by the following:
• Hemoglobin ≥ 9.0 g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal range (ULN) (unless liver metastases are present, then ≤ 5 × ULN is allowed)
• Total bilirubin ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN
• ANC ≥ 1.5 × 109/L
• Platelets ≥ 100 × 109/L
• International Normalized Ratio for prothrombin time (PT-INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) within normal limits
• Patients must be able to swallow and retain oral medications.

You may not qualify if:

• Known untreated brain metastasis.
• Prior irradiation to \> 25% of the bone marrow (whole pelvis = 25%).
• Any previous major surgery within 4 weeks of the start of the study, or within 1 week of any minor surgical procedure (e.g., dental work, port placement, etc.).
• Treatment with chemotherapy or an investigational new drug within 28 days of day 1 of treatment.
• No prior anti-vascular endothelial growth factor (VEGF) therapy (with the exception of bevacizumab if the last dose was \> 3 months prior to study treatment), including VEGF receptor inhibitors, thalidomide or thalidomide-like therapy, or any other (including investigational) anti-angiogenic treatment of any kind. Only prior bevacizumab is allowed.
• Patients with any serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.
• Evidence or history of bleeding diathesis or coagulopathy.
• Any serious non-healing wound, ulcer, or bone fracture.
• Cardiac disease, including: congestive heart failure (CHF) \> Class II per New York Heart Association (NYHA) classification (see Appendix B); unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, cardiac arrhythmia, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension (i.e., systolic blood pressure \> 150 mm Hg or diastolic pressure \> 90 mm Hg despite optimal medical management).
• Psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Patients with a history of DVT/PE are not allowed if the thrombosis occurred within the last 6 months.
• Pulmonary hemorrhage or bleeding event \> grade 2 within 4 weeks of study randomization.
• Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of study randomization.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Bayer: collaborator

Study Sites (1)

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Capecitabine; Sorafenib

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jeffrey Infante, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: February 12, 2008
• Study Start: February 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2010
• Last Updated: February 4, 2013

Record last verified: 2013-01

Locations

US (1)