Ph II of Capecitabine, Carboplatin & Bevacizumab for Gastroesophageal Junction & Gastric Carcinoma
Condition: Stomach Cancer; Gastric (Stomach) Cancer; Neoplasm of Cardioesophageal Junction; Gastrointestinal Stromal Tumor (GIST)
MeSH terms: Gastrointestinal Stromal Tumors; Stomach Neoplasms
Intervention: bevacizumab; carboplatin; capecitabine
Intervention description: Intravenous 15 mg/kg; AUC 6, Intravenously Day 1 every 21 days; 850mg/m2, Orally twice daily days 1-14 every 21 days.
Intervention MeSH terms: Bevacizumab; Carboplatin; Capecitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To investigate bevacizumab in combination with carboplatin and capecitabine for patients with
      unresectable or metastatic GEJ or gastric cancers. We hope that by adding bevacizumab to
      standard chemotherapy for this patient population we will improve Progression Free Survival
      by 90% over historical controls.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects must be treated at Stanford University Medical Center for the entire length of
        study participation.

          1. Patients with histologically or cytologically confirmed adenocarcinoma of the GEJ or
             stomach.

          2. Patients must be deemed unresectable due to involvement of critical vasculature or
             adjacent organ invasion. If unresectable, patients must show evidence of disease
             progression prior to enrollment.

          3. Patients with prior surgical resection who develop radiological or clinical evidence
             of metastatic cancer do not require separate histological or cytological confirmation
             of metastatic disease unless an interval of > 5 years has elapsed between the primary
             surgery and the development of metastatic disease. Clinicians should consider biopsy
             of lesions to establish diagnosis of metastatic disease if there is substantial
             clinical ambiguity regarding the nature or source of apparent metastases.

          4. Prior carboplatin as neoadjuvant or adjuvant therapy will be allowed if >= 6 months
             from the time of study entry.

          5. If patients use aspirin (>325mg/day) or NSAIDS at the time of enrollment, they must
             have a 10 day washout period prior to beginning protocol treatment.

          6. Low molecular weight heparin (or its equivalent, excluding warfarin) will be allowed
             for treatment of venous thromboembolic events if patients have no evidence of bleeding
             on full-dose anticoagulation.

          7. Patients must have a primary or metastatic lesion measurable in at least one dimension
             by Modified RECIST criteria (see Section 11.2.3) within 4 weeks prior to entry of
             study

          8. Patients must have ECOG performance status of 0-1

          9. Patients must be >= 18 years of age

         10. Laboratory values <= 2 weeks prior to randomization:

               -  Absolute Neutrophil Count (ANC) >= 1.5 x 109/L (>= 1500/mm3)

               -  Platelets (PLT) >= 100 x 109/L (>= 100,000/mm3)

               -  Hemoglobin (Hgb) >= 9 g/dL

               -  Serum creatinine <= 1.5 x ULN

               -  Serum bilirubin <= 1.5 x ULN (<= 3.0 x ULN if liver metastases present)

               -  Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) <= 3.0
                  x ULN (<= 5.0 x ULN if liver metastases present). Note: ERCP or percutaneous
                  stenting may be used to normalize the liver function tests.

         11. Life expectancy >= 12 weeks

         12. Inclusion and exclusion criteria for DCE-MRI and DWI imaging will be determined by CT
             scan as part of routine post-chemotherapy imaging. Subjects will be eligible if one
             liver metastasis is greater than 1 cm in size. Participation in the DCE-MRI and DWI
             correlate is not required for eligibility.

         13. Ability to give written informed consent according to local guidelines

        Exclusion Criteria:

          1. Disease-Specific Exclusions

               1. Prior chemotherapy for metastatic disease

               2. Prior full field radiotherapy <= 4 weeks or limited field radiotherapy <= 2 weeks
                  prior to enrollment. Patients must have recovered from all therapy-related
                  toxicities. The site of previous radiotherapy should have evidence of progressive
                  disease if this is the only site of disease.

               3. Prior biologic or immunotherapy <= 2 weeks prior to registration. Patients must
                  have recovered from all therapy-related toxicities

               4. Prior therapy with anti-VEGF agents

               5. If history of other primary cancer, subject eligible only if she or he has:

                    -  Curatively resected non-melanomatous skin cancer

                    -  Curatively treated cervical carcinoma in situ

                    -  Other primary solid tumor curatively treated with no known active disease
                       present and no treatment administered for the last 3 years

               6. Concurrent use of other investigational agents and patients who have received
                  investigational drugs <= 4 weeks prior to enrollment.

               7. Hypersensitivity to capecitabine, fluorouracil, or any component of the
                  formulation and or a known deficiency of dihydropyrimidine dehydrogenase.

          2. General Medical Exclusions

               1. Subjects known to have chronic or active hepatitis B or C infection

               2. History of any medical or psychiatric condition or laboratory abnormality that in
                  the opinion of the investigator may increase the risks associated with study
                  participation or study drug administration or may interfere with the conduct of
                  the study or interpretation of study results

               3. Male subject who is not willing to use adequate contraception upon enrollment
                  into this study and for 6 months following the last dose of second-line treatment

               4. Female subject (of childbearing potential, post-menopausal for less than 6
                  months, not surgically sterilized, or not abstinent) who is not willing to use an
                  oral, patch or implanted contraceptive, double-barrier birth control, or an IUD
                  during the course of the study and for 6 months following the last dose of
                  second-line treatment

               5. Female subject who is breast-feeding or who has positive serum pregnancy test 72
                  hours prior to randomization

               6. Pleural effusion or ascites that causes respiratory compromise (>= CTCAE grade 2
                  dyspnea)

               7. Any of the following concurrent severe and/or uncontrolled medical conditions
                  within 24 weeks of enrollment which could compromise participation in the study:

                    -  Unstable angina pectoris

                    -  Symptomatic congestive heart failure

                    -  Myocardial infarction <= 6 months prior to registration and/or randomization

                    -  Serious uncontrolled cardiac arrhythmia

                    -  Uncontrolled diabetes

                    -  Active or uncontrolled infection

                    -  Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of
                       the lung.

                    -  Chronic renal disease

                    -  Acute or chronic liver disease (e.g., hepatitis, cirrhosis)

               8. Patients unwilling to or unable to comply with the protocol

               9. Life expectancy of less than 12 weeks

              10. Current, recent (within 4 weeks of the first infusion of this study), or planned
                  participation in an experimental drug study other than a Genentech-sponsored
                  bevacizumab cancer study

          3. Bevacizumab-Specific Exclusions

               1. Inadequately controlled hypertension (defined as systolic blood pressure >150
                  and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)

               2. Any prior history of hypertensive crisis or hypertensive encephalopathy

               3. New York Heart Association (NYHA) Grade II or greater congestive heart failure
                  (see Appendix A)

               4. History of myocardial infarction or unstable angina within 6 months prior to
                  study enrollment

               5. History of stroke or transient ischemic attack within 6 months prior to study
                  enrollment

               6. Known CNS disease, brain metastases.

               7. Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

               8. Symptomatic peripheral vascular disease

               9. Evidence of bleeding diathesis or coagulopathy

              10. Major surgical procedure, open biopsy, or significant traumatic injury within 28
                  days prior to study enrollment or anticipation of need for major surgical
                  procedure during the course of the study

              11. Core biopsy or other minor surgical procedure, excluding placement of a vascular
                  access device, within 7 days prior to study enrollment

              12. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
                  abscess within 6 months prior to study enrollment

              13. Serious, non-healing wound, ulcer, or bone fracture

              14. Urine protein >= 2+ on urinalysis dipstick and >= 1.0 gram on 24-hour urine
                  collection

              15. Known hypersensitivity to any component of bevacizumab

              16. History of hemoptysis (bright red blood of ½ teaspoon or more per episode) within
                  3 months prior to study enrollment.

              17. Current, ongoing treatment with full-dose warfarin.