TITLE: UAB 0717 - A Phase 2 Study of XL880 Administered Orally to Patients with poorly differentiated diffuse metastatic gastric cancer
SPONSOR: Exelixis, Inc.
Investigator: James A. Posey, III, MD
OBJECTIVES
1. To determine the best confirmed response rate of XL880 treatment in subjects with poorly differentiated gastric carcinoma.
2. To further evaluate the safety and tolerability of XL880.
3. To assess the progression-free survival, duration of response, and overall survival in subjects with gastric carcinoma who are treated with XL880.
4. To characterize the pharmacokinetic and pharmacodynamic parameters of XL880 in subjects with gastric carcinoma.
5. To characterize the 7q31 amplification status of patients in this study population and possible associations with response to XL880 therapy.
INCLUSION CRITERIA
1. The subject has a histologically confirmed diagnosis of poorly differentiated metastatic gastric carcinoma. A histologic diagnosis of Signet Ring Gastric carcinoma will be considered poorly differentiated Subjects with tumors of the gastroesophogeal junction may be eligible provided that the following are true:
a. The tumor is not of Squamous histology or has a component of Barrett's esophagus and
b. There is surgical or endoscopic documentation verifying the gastric, rather than the esophageal, origin of the tumor.
2. Ten unstained slides of tumor tissue, archival or fresh, have been received at the central analysis laboratory.
3. The subject has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20mm with conventional techniques or as ≥ 10mm with spiral CT scan.
4. The subject is at least 18 years old.
5. The subject has an ECOG Performance Status ≤ 2.
6. The subject is able to ingest XL880 capsules.
7. In the adrenocorticotropic hormone (ACTH) stimulation test, the subject has a serum cortisol level ≥ 20µg/dL (552nmol/L) 30-90 minutes after injection of ACTH.
8. The subject has organ and marrow functions as follows:
a. ANC ≥ 1500/mm3
b. Platelets ≥ 100,000/dL
c. Hemoglobin ≥ 9g/dL
d. Bilirubin ≤ 1.5mg/dL
e. Serum Creatinine ≤ 1.5mg/dL or
f. Creatinine Clearance ≥ 60mL/min.
g. ALT and AST ≤ 2.5 times the upper limit of normal if no liver involvement or ≤ 5 times the upper limit of normal with liver involvement.
9. The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
10. Sexually active subjects (male and female) must use a medically accepted method of contraception during the course of the study.
11. Female subjects of childbearing potential must have a negative serum pregnancy test at screening.
12. The subject has no other diagnosis of malignancy (unless non-melanoma skin cancer or a malignancy diagnosed ≥ 5 years ago, and has no evidence of disease for 5 years prior to screening for this study).
EXCLUSION CRITERIA
1. The subject has received radiotherapy to ≥ 25% of his or her bone marrow within 30 days of initial treatment with XL880.
2. The subject has received more than one line of prior cytotoxic chemotherapy for locally advanced or metastatic disease. For the purpose of this protocol, neoadjuvant therapy would not be considered to be prior cytotoxic chemotherapy.
3. The subject has received an investigational drug within 30 days of the first dose of study drug.
4. The subject has received chemotherapy, immunotherapy, or radiotherapy within 30 days or has received nitrosoureas or mitomycin C within 6 weeks prior to the scheduled first dose of XL880.
5. The subject has adverse events due to investigational drugs or other medications administered more than 30 days prior to enrollment that have not recovered to Grade ≤ 1 using NCI CTCAE v3.0.
6. The subject has known brain metastases.
7. The subject has uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
8. The subject is pregnant or breastfeeding.
9. The subject is known to be positive for the HIV virus.
10. The subject has an allergy or hypersensitivity to components of the XL880 formulation.
11. The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
ADDITIONAL INFORMATION
Contact: Dayle Craig,R.N.
Telephone: 205-975-8080
Email: dayle.craig@ccc.uab.edu