Abraxane in CIMP-High Colorectal and Small Bowel Adenocarcinomas

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01730586
First received: October 26, 2012
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Cancer of Gastrointestinal Tract
Drug: Abraxane
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Abraxane in CIMP-High Colorectal Adenocarcinomas and Small Bowel Adenocarcinomas

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

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: 35
Study Start Date: November 2012
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abraxane
Abraxane 220 mg/m2 administered by vein on Day 1. A cycle of therapy is defined as 21 days.
Drug: Abraxane
220 mg/m2 administered by vein on Day 1. A cycle of therapy is defined as 21 days.
Other Names:
  • Nab-Paclitaxel
  • Paclitaxel (Protein-Bound)
  • ABI-007

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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-EGFR therapy if 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 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 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.
  Contacts and Locations
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

Contacts
Contact: Michael Overman, MD 713-745-4317

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Celgene Corporation
Investigators
Principal Investigator: Michael Overman, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01730586     History of Changes
Other Study ID Numbers: 2012-0776, NCI-2013-00077
Study First Received: October 26, 2012
Last Updated: April 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Adenocarcinoma
Colorectal Neoplasms
Gastrointestinal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014