Postoperative Chemotherapy in High-Grade Appendiceal Adenocarcinoma With Peritoneal Carcinomatosis

This is an observational, single-cohort, prospective study of systemic chemotherapy after
CRS/HIPEC. Subjects will be given twelve months of 5-FU or capecitabine with bevacizumab
starting 4-16 weeks after surgery. CTRI Biostatistics Core personnel will assist in
conducting analyses using the latest version of R (R Foundation for Statistical Computing,
Vienna, Austria. http://www.R-project.org/).

No therapy is included in this study. Subjects have already previously undergone surgery for
their cancer. This study will observe the outcomes of the postoperative chemotherapy
treatment the doctor chooses to treat the subject's cancer.

3.1 Inclusion Criteria Patients must meet all of the inclusion criteria to participate in
this study.

1. Ability to understand and the willingness to sign a written informed consent.

2. High-grade peritoneal carcinomatosis from appendiceal adenocarcinoma.

1. Moderate or poorly-differentiated adenocarcinoma, signet ring cell carcinoma or
"high-grade" carcinoma (in primary tumor or extra-appendiceal metastases) as
designated by standardized pathologic testing.23,24

2. May be initially determined from pre-CRS/HIPEC tumor pathology (for screening
purposes), but must be confirmed with pathology from resected tumors as part of
CRS/HIPEC.

3. Have had complete (CC-0 or CC-1) CRS with HIPEC open or minimally invasive
(laparoscopic or robotic)

4. Have received or plan to receive 12 months of postoperative chemotherapy, starting no
sooner than 4 weeks and no longer than 16 weeks after CRS/HIPEC, consisting of:

1. 5-fluorouracil (Adrucil®) 400 mg/m2 IV bolus then 2400 mg/m2 IV continuous
infusion x 46hrs, leucovorin (Leucovorin Calcium) 20 mg/m2 IV bolus and
bevacizumab (Avastin®) 5 mg/kg IV every two weeks for a total of 12 months (26
cycles); OR

2. Capecitabine (Xeloda®) 1250 mg/m2 PO twice daily for 14 days, with 7-day break,
bevacizumab (Avastin®) 7.5 mg/kg IV every three weeks, for a total of 12 months
(17 cycles).

5. Have received or plan to receive standard clinical, biochemical and radiographic
surveillance, consisting of:

1. Adverse event assessments every chemotherapy cycle and at the end of treatment

2. CEA, CA19-9 and CA 125

i) Every 1 month x 1 year (during treatment), then ii) Every 1 month x 6 months, then
iii) Every 3 months x 1.5 years, then iv) Every 6 months x 1 year c) CT chest, abdomen
and pelvis or MRI i) Every 3 months x 1 year (during treatment), then ii) Every 3
months x 1 year, then iii) Every 6 months x 1 year, then iv) Every 12 months x 1 year

6. Age > 18 years old

7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 (Appendix A).

8. Adequate organ and bone marrow function as defined below:

1. Absolute Neutrophil Count ≥ 1.5 x 109/L

2. Platelet count ≥ 100 x 109/L

3. Hemoglobin ≥ 9.0 g/dL

4. Total bilirubin ≤ 1.5 x ULN

5. AST/SGOT and ALT/SPGT ≤ 2.5 X ULN

6. Serum creatinine ≤ 1.5 x ULN

9. Women of child-bearing potential and men with partners of child-bearing potential 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.

a) A woman of child-bearing potential is any female (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria: i) Has not undergone a hysterectomy or bilateral oophorectomy; or
ii) 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)

10. Women of child-bearing potential must have negative pregnancy test prior to initiating
study drug treatment.

3.2 Exclusion Criteria Subjects meeting any of the exclusion criteria at baseline will be
excluded from study participation.

1. Current or anticipated use of other investigational agents.

2. Patients who have received systemic chemotherapy or radiotherapy within two months
prior to first scheduled cycle of postoperative chemotherapy.

3. Patients who are less than 4 weeks from CRS/HIPEC or have insufficient recovery from
surgical-related trauma or wound healing as determined by the patient's surgeon.

4. History of hypersensitivity reaction specifically attributed to compounds of similar
chemical or biologic composition to 5-FU, leucovorin, capecitabine or bevacizumab.

5. History of deep venous thrombosis (DVT) or pulmonary embolism (PE).

6. Concurrent active or measurable malignancies, except basal cell carcinoma or squamous
cell carcinoma of the skin.

7. Severe or uncontrolled medical disorder that would, in the investigator's opinion,
impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal
disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric
illness/social situations that would limit compliance with study requirements).

8. Known diagnosis of human immunodeficiency virus (HIV) infection.

9. Incarcerated patients.

10. Pregnant or nursing women, due to the potential for congenital abnormalities and for
this regimen to harm nursing infants.