Sorafenib Plus Capecitabine (SorCape) in Previously Treated Metastatic Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Florida
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01471353
First received: November 10, 2011
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

Combining Sorafenib with standard cytotoxic fluoropyrimidine therapy for advanced colorectal cancer may provide clinical benefit when no other treatment remains.


Condition Intervention Phase
Colorectal Cancer Metastatic
Drug: Sorafenib Plus Capecitabine (SorCape)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sorafenib Plus Capecitabine (SorCape) in Previously Treated Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Sorafenib activity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Determine activity of sorafenib plus capecitabine on progression free survival (PFS) in patients with advanced colorectal cancer.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Evaluate overall survival after treatment.

  • Progression free survival [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Evaluate progression free survival at 3 months after treatment

  • Response rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Measure response rate to treatment

  • Time to progression [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
    Time to disease progression while on and/or after treatment complete

  • Toxicity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Evaluate acute toxicity of treatment

  • Correlative tissue analysis [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Exploratory tissue analysis in patients receiving sorafenib plus capecitabine


Estimated Enrollment: 43
Study Start Date: November 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib Plus Capecitabine (SorCape)
Sorafenib 200-400 mg PO twice daily on days 1-21 (dose escalation schema) plus Capecitabine 1000 mg/m2 PO twice daily on days 1-14 repeated every 21 days. Single arm study.
Drug: Sorafenib Plus Capecitabine (SorCape)
Sorafenib 200-400 mg PO twice daily on days 1-21 (dose escalation schema) plus Capecitabine 1000 mg/m2 PO twice daily on days 1-14 repeated every 21 days
Other Names:
  • Nexavar
  • Xeloda
  • Chemotherapy

Detailed Description:

The Raf/MEK/ERK pathway is an important mediator of responses to growth factors, and a strong inducer of genes involved in tumorigenesis, angiogenesis, apoptosis, and tumorigenesis in metastatic colorectal cancer (mCRC). Inhibition of this pathway has been previously proven to be highly clinically beneficial for patients with this disease. It has also been clearly demonstrated that the inhibition of VEGF, when coupled with cytotoxic therapy and/or continued beyond initial response, can improve clinical outcomes and survival in this same cohort of patients. Safety and pharmacokinetic data have already been established for this novel doublet oral chemotherapy. This study is intended to determine the activity of a combination of oral fluoropyrimidine plus sorafenib in an advanced mCRC patient population for whom limited treatment options remain.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically proven adenocarcinoma of the colon or rectum.
  • Metastatic disease that is not amenable to potentially curative treatment.
  • Measurable disease (as per RECIST 1.1 criteria).
  • At least one prior chemotherapeutic regimen for metastatic disease. Patients must have progressed following oxaliplatin based therapy (in either the adjuvant or metastatic setting) and irinotecan based therapy (in the metastatic setting).
  • Adequate bone marrow, liver and renal function.
  • Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate, provided stability in anticoagulation therapy is documented at the treating provider's discretion. For patients on warfarin, the INR should be measured prior to the initiation of study treatment and should be monitored at least weekly, or as defined by the local standard of care, until INR is stable.
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
  • Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
  • Patients may have had a history of other (non-colorectal) malignancies if there is no current evidence of persistent or recurrent disease and they are not undergoing any active therapy (including hormonal).
  • Patients should have paraffin-embedded tissue from initial diagnosis or prior colorectal cancer surgery available for molecular analysis.
  • Patients must consent to participate in the study and must have signed and dated an IRB-approved consent form conforming to federal and institutional guidelines. Consent must be obtained prior to any study specific procedures.

Exclusion Criteria:

  • Prior therapy with a tyrosine kinase inhibitor.
  • Age < 18 years
  • ECOG Performance Status > 2
  • Less than 28 days elapsed from prior radiation therapy, surgery or chemotherapy to the time of registration.
  • History of known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
  • History of clinically significant cardiac disease (severe/unstable angina pectoris, NYHA class III or IV congestive heart failure, symptomatic coronary artery disease) or myocardial infarction, cerebrovascular accident or transient ischemic attack within the last 12 months.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg, as measured on 3 consecutive pre-enrollment assessments, despite optimal medical management.
  • Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
  • Active clinically serious infection > CTCAE Grade 2.
  • Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
  • Pulmonary embolism or any other uncontrolled thromboembolic event within 3 months prior to registration or occurrence of deep vein thrombosis within 4 weeks of registration.
  • Serious non-healing wound, ulcer, or bone fracture.
  • Evidence or history of a clinically significant bleeding diathesis or coagulopathy (without vitamin K antagonist therapy).
  • Use of St. John's Wort or rifampin (rifampicin).
  • Known or suspected allergy to sorafenib or capecitabine.
  • Any condition that impairs patient's ability to swallow whole pills.
  • Any known malabsorption problem.
  • History of chronic or inflammatory bowel disorders, clinically significant chronic diarrhea refractory to medical management, or unresolved bowel obstruction.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01471353

Contacts
Contact: Alison Ivey, RN 352-265-0680 ext 88411 aivey@ufl.edu
Contact: Kevin Tormes, RN 352-265-0680 ext 87617 ktormes@ufl.edu

Locations
United States, Florida
UF Health Cancer Center Recruiting
Gainesville, Florida, United States, 32610
Contact: Alison Ivey, RN    352-265-0680 ext 88411    aivey@ufl.edu   
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Thomas George, MD, FACP University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01471353     History of Changes
Other Study ID Numbers: ONC2010-23
Study First Received: November 10, 2011
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
Metastatic
Colon Cancer
Rectal Cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Fluorouracil
Sorafenib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014