Abraxane in CIMP-High Colorectal and Small Bowel Adenocarcinomas
Verified August 2014 by M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
First received: October 26, 2012
Last updated: August 8, 2014
Last verified: August 2014
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.
Cancer of Gastrointestinal Tract
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase II Study of Abraxane in CIMP-High Colorectal Adenocarcinomas and Small Bowel Adenocarcinomas
Primary Outcome Measures:
- Response Rate in CIMP-High Colorectal Cancer and Small Bowel Adenocarcinoma [ Time Frame: 21 days ] [ Designated as safety issue: No ]
Sample size of 15 patients with CIMP-high required to demonstrate a response rate of 20% using a binomial one-sample test with a two-sided alpha of 0.025 and power of 91%. For second disease group, 10 small intestinal adenocarcinomas patients enrolled to test if a null hypothesis of ≤1% response rate is different from an alternative hypothesis of a response rate of 20% using a binomial one-sample test with a two-sided alpha of 0.025 and power of 0.85. A Bonferroni's correction used to account for the multiple testing (overall alpha=0.05/2 tests). Pearson chi-square (or Fisher's exact test) or t-test (or Wilcoxon rank test) used to determine differences between responder and non-responders.
Secondary Outcome Measures:
- Progression-Free Survival [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
Overall survival and time to progression functions will be estimated using the Kaplan-Meier method. Patients who drop out of the study will be included in the time to event data analysis as "censored data". For progression-free survival as a binary endpoint, the intent-to-treat analysis will be performed using all available patients. A two-sided log-rank test will be used to assess the differences of time to events between groups.
| Estimated Enrollment:
| Study Start Date:
| Estimated Primary Completion Date:
||November 2016 (Final data collection date for primary outcome measure)
Abraxane 220 mg/m2 administered by vein on Day 1. A cycle of therapy is defined as 21 days.
220 mg/m2 administered by vein on Day 1. A cycle of therapy is defined as 21 days.
- Paclitaxel (Protein-Bound)
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Patient must have histologically or cytologically confirmed colorectal adenocarcinoma or small bowel adenocarcinoma
- Metastatic disease documented on diagnostic imaging studies with measurable disease per RECIST version 1.1.
- Refractory disease defined as: a) prior treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-EGFR therapy if KRAS wildtype for colorectal adenocarcinoma and; b) prior treatment with fluoropyrimidine and oxaliplatin for small bowel adenocarcinoma.
- 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).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
- 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 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.
- 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.
- 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.
- 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.
- Patient is =/>18 years of age on the day of consenting to the study.
- 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)".
- Prior treatment with taxane therapy for either colorectal cancer or small bowel adenocarcinoma.
- 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.
- 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.
- Pregnancy (positive pregnancy test) or lactation.
- Patients with carcinomatous meningitis.
- Known 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01730586
|Contact: Michael Overman, MD
|University of Texas MD Anderson Cancer Center
|Houston, Texas, United States, 77030 |
M.D. Anderson Cancer Center
||Michael Overman, MD
||UT MD Anderson Cancer Center
No publications provided
||M.D. Anderson Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 26, 2012
||August 8, 2014
||United States: Food and Drug Administration
Keywords provided by M.D. Anderson Cancer Center:
Cancer of Gastrointestinal Tract
CIMP-high Colorectal Adenocarcinoma
Small Bowel Adenocarcinomas
Small bowel cancer
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on October 21, 2014
Digestive System Diseases
Digestive System Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Antineoplastic Agents, Phytogenic
Molecular Mechanisms of Pharmacological Action