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

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

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: Sorafenib Plus Capecitabine (SorCape)

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.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Xeloda; Nexavar; Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sorafenib Activity	Determine activity of sorafenib plus capecitabine on progression free survival (PFS) in patients with advanced colorectal cancer. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Evaluate overall survival after treatment.	5 years
Response Rate	This is the percentage of subjects that achieved either a complete response or a partial response per RECIST 1.1 criteria	3 months
Response Duration	This is the median response duration (median time from date of a complete or partial response to date of disease progression per RECIST 1.1 criteria) and includes only subjects that achieved either a complete or partial response to treatment per RECIST 1.1 criteria.	up to 12 months
Toxicity (Percentage of Subjects That Experienced an Adverse Event)	Evaluate acute toxicity of treatment. The toxicity assessments were graded by the NCI CTCAE (Clinical Trial Common Adverse Event) grading system - a global standard for assessments of clinical and laboratory toxicities. All toxicities are scored 1(mild) through 5 (death related to the event) based upon well-defined and reproducible definitions.	12 months
Correlative Tissue Analysis	Exploratory tissue analysis in patients receiving sorafenib plus capecitabine	6 months

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Bayer
• Investigators: Principal Investigator: Thomas George, MD, FACP, University of Florida

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: November 10, 2011
• First Submitted That Met QC Criteria: November 15, 2011
• First Posted (Estimate): November 16, 2011

Study Record Updates

• Last Update Posted (Actual): July 23, 2020
• Last Update Submitted That Met QC Criteria: July 21, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Metastatic; Rectal Cancer; Colon Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib; Capecitabine
• Other Study ID Numbers: ONC2010-23; IRB201701484 (Other Identifier: University of Florida conversion#)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No