Abraxane in CIMP-High Colorectal and Small Bowel Adenocarcinomas
Condition: Colorectal Cancer; Cancer of Gastrointestinal Tract
MeSH terms: Colorectal Neoplasms; Adenocarcinoma; Gastrointestinal Neoplasms
Intervention: Abraxane
Intervention description: 220 mg/m2 administered by vein on Day 1. A cycle of therapy is defined as 21 days.
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colorectal Cancer; Cancer of Gastrointestinal Tract; CIMP-high Colorectal Adenocarcinoma; Small Bowel Adenocarcinomas; Colorectal; Small bowel cancer; Abraxane; Nab-Paclitaxel; Paclitaxel (Protein-Bound); ABI-007

Summary:

      The goal of this clinical research study is to learn if abraxane can help to control
      colorectal and/or small bowel cancer. The safety of this drug will also be studied.

      Abraxane is designed to block cancer cells from dividing, which may cause them to die.
    

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.