Abraxane in CIMP-High Colorectal and Small Bowel Adenocarcinomas

Launched by M.D. ANDERSON CANCER CENTER · Nov 15, 2012

Keywords

ClinConnect Summary

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive the study drug in 21-day study cycles.

You will receive abraxane by vein over about 30 minutes on Day 1 of each cycle.

Study Visits:

On Day 1 of all cycles, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your weight and blood pressure.
* You will be asked about any drugs you may be taking and about any symptoms or side effects you may be having.
* Your performance status will be recorded.
* Blood (about 2 tablespoons) w...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Patient must have histologically or cytologically confirmed colorectal adenocarcinoma or small bowel adenocarcinoma
• • 2. Metastatic disease documented on diagnostic imaging studies with measurable disease per RECIST version 1.1.
• • 3. Refractory disease defined as: a) prior treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-epidermal growth factor receptor (EGFR) therapy if Kirsten rat sarcoma (KRAS) wildtype for colorectal adenocarcinoma and; b) prior treatment with fluoropyrimidine and oxaliplatin for small bowel adenocarcinoma.
• • 4. Colorectal adenocarcinoma patients must be known to have CpG island methylator phenotype. CIMP-high phenotype will be defined as hypermethylation at 2 or more of the 6 methylation-specific PCR markers (hMLH1, P16, P14, MINT1, MINT2, and MINT31).
• • 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
• • 6. Adequate organ function including: a) Absolute neutrophil count (ANC) =/\>1,500cells/mm\^3; b) Platelets =/\>100,000/ul; c) Hemoglobin \>9.0 g/dL; d) Total bilirubin =/\<1.5mg/dL In patients with known Gilbert's syndrome, direct bilirubin =/\<1.5 x upper limit of normal (ULN) will be used as organ function criteria, instead of total bilirubin; e) AST and ALT \< 2.5 x ULN; f) Alkaline phosphatase \<2.5x ULN; g) Creatinine \<1.5 gm/dL.
• • 7. Negative serum or urine pregnancy test in women with childbearing potential (WOCBP) defined as not post-menopausal for 12 months or no previous surgical sterilization, within one week prior to initiation of treatment. WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy.
• • 8. A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy. If the partner is pregnant or breastfeeding, the subject must use a condom.
• • 9. Patients must sign an Informed Consent and Authorization indicating that they are aware of the investigational nature of this study and the known risks involved.
• • 10. Patient is =/\>18 years of age on the day of consenting to the study.
• Exclusion Criteria:
• • 1. Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.0. In CTCAE version 4.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)".
• • 2. Prior treatment with taxane therapy for either colorectal cancer or small bowel adenocarcinoma.
• • 3. Chemotherapy or any other investigational agents within 14 days of first receipt of study treatment, or major surgery within 28 days of first receipt of study treatment, or palliative radiation within 7 days of first receipt of study treatment.
• • 4. Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, uncontrolled diabetes, serious active or uncontrolled infection.
• • 5. Pregnancy (positive pregnancy test) or lactation.
• • 6. Patients with carcinomatous meningitis.
• • 7. Known central nervous system (CNS) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.