Bavituximab, Capecitabine, and Radiation Therapy in Treating Patients with Stage II-III Rectal Cancer
- Biopsy-proven invasive adenocarcinoma of the rectum, stage T3-4 and/or node-positive (American Joint Committee on Cancer [AJCC] stage II or III) per AJCC staging manual, 7th edition; patients with M1a rectal cancer (“metastasis confined to one organ or site [e.g., liver, lung, ovary, non regional node]"), stage IVA disease per the AJCC staging manual, 7th edition, are also eligible; for the purpose of this study, a tumor is located in the “rectum” when its distal edge is located =< 12cm from the anal verge; the distal edge of the tumor can be delineated by digital examination or endoscopic examination, including colonoscopy, although rigid proctoscopy is preferred
- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale is required
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcl
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine < 1.5 x institutional upper limits of normal
- Activated partial thromboplastin time (aPTT) =< 1.5 x institutional upper limits of normal
- No additional screening intended for human immunodeficiency virus (HIV) or hepatitis infection
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: ** Has not undergone a hysterectomy or bilateral oophorectomy ** Or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- Ability to understand and the willingness to sign a written informed consent
- Known history of bleeding diathesis or coagulopathy (e.g., von Willebrand disease or hemophilia)
- Bleeding * Clinically significant bleeding, such as gross hematuria, gastrointestinal bleeding (excluding bleeding from rectal tumor), and hemoptysis within the 12 months before screening; if clinically significant bleeding has occurred within 12 months of screening but the cause has been identified and adequately treated (e.g., cystitis, ulcer), then this exclusion criterion does not apply * Minor biopsy-related bleeding lasting < 24 hours and resolved at least 1 week before Study Day 1 is allowed
- Venous thromboembolic events (e.g., deep vein thrombosis or pulmonary embolism) within 6 months of screening
- Ongoing therapy with oral or parenteral anticoagulants; low-dose anticoagulation to maintain patency of lines is allowed
- Concurrent estrogens, anti-estrogens or progesterone compounds
- Any prior radiation for rectal cancer
- Symptomatic or clinically active brain metastases
- Major surgery within 4 weeks of Study Day 1
- Pregnant or nursing women
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, history of blood clotting abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements
- Symptomatic coronary artery disease, cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina pectoris within 6 months of screening
- Known chronic infection with human immunodeficiency virus (HIV) or viral hepatitis
- Known hypersensitivity to any components of the treatments
- History of malignancy other than non-melanoma skin cancers within 5 years prior to study enrollment
- Subjects receiving other investigational agents thirty days prior to study treatment or during treatment
- History of inflammatory bowel disease
I. To determine dose-limiting toxicities (DLT) and maximally tolerated dose (MTD) for bavituximab when administered on a weekly basis concurrently with external beam radiation therapy.
I. To describe the adverse events associated with bavituximab when administered on a weekly basis concurrently with external beam irradiation and capecitabine.
II. To describe any preliminary evidence of anti-tumor activity by assessment of objective response as determined by magnetic resonance (MR) imaging and histopathological response in patients with T3-4 and/or node-positive rectal adenocarcinoma.
I. To determine if the combination of bavituximab, capecitabine, and radiation therapy induces changes in tumor-vasculature parameters as assessed by dynamic contrast-enhanced (DCE)-MR imaging (MRI), in selected patients.
II. Establish biomarkers for the efficacy of the combination therapy and to better define the mechanism of action of the therapeutics.
OUTLINE: This is a dose-escalation study of bavituximab.
Patients receive bavituximab intravenously (IV) over 90 minutes on Friday of each week for 8 weeks and capecitabine orally (PO) twice daily (BID) Monday-Friday of each week of radiation therapy for 6 weeks. Patients undergo external beam radiation therapy daily Monday-Friday for approximately 6 weeks. Patients also undergo surgery 4-8 weeks following the last dose of bavituximab. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 28 days and then every 3 months for 1 year, every 6 months for 1 year, and annually thereafter (at the discretion of the treating physicians).
Trial Phase Phase I
Trial Type Treatment
UT Southwestern / Simmons Cancer Center-Dallas
Jeffrey John Meyer
- Primary ID STU 032012-025
- Secondary IDs NCI-2014-02136, NCI-2014-01729, NCI-2014-01933, 8843
- Clinicaltrials.gov ID NCT01634685