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Phase II Study of Abraxane in CIMP-High Colorectal Adenocarcinomas and Small Bowel Adenocarcinomas


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Colorectal Cancer, Cancer of Gastrointestinal Tract

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Trial Information

Phase II Study of Abraxane in CIMP-High Colorectal Adenocarcinomas and Small Bowel Adenocarcinomas


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) will be drawn for routine tests.

At the end of every 3rd cycle (Cycles 3, 6, 9) and so on:

-You will have a CT or MRI scan of your chest, abdomen, and pelvis to check the status of
the disease. If at any point the scans show the disease appearing to get better, you will
have another scan 2 cycles later.

Length of Treatment:

You may continue taking the study drug for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug if the disease gets worse, if
you have intolerable side effects, if the study is stopped, or if you are unable to follow
study instructions.

Your participation on the study will be over after the follow-up period.

End-of-Treatment Visit:

Within 10 days after you stop taking the study drug, you will have an end-of-treatment
visit. At this visit, 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) will be drawn for routine tests.

- If one has not been performed in the previous 4 weeks, you will have a CT or MRI scan
of your chest, abdomen, and pelvis to check the status of the disease.

Follow-Up:

The study staff will ask about any symptoms or side effects you may be having during the 30
days after your last dose of the study drugs. The study staff may ask you by phone or at
the time of a routine clinic visit. If the study staff contacts you by phone, the phone
call should last about 15-30 minutes.

If you leave the study for any reason other than the disease getting worse, you will have a
CT or MRI scan of your chest, abdomen, and pelvis to check the status of the disease every
12 weeks unless you start receiving other treatment.

The study staff will also review your medical records and/or contact you to check the status
of the disease every 3 months after you stop receiving the study drug. If you are contacted
by phone, each phone call should take about 5 minutes.

This is an investigational study. Abraxane is FDA approved and commercially available for
the treatment of breast cancer. It is not FDA approved for the treatment of colorectal or
small bowel cancer. The use of abraxane in patients with colorectal cancer or small bowel
cancer is investigational.

Up to 25 patients will take part in this study. All will be enrolled at MD Anderson.


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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response Rate in CIMP-High Colorectal Cancer and Small Bowel Adenocarcinoma

Outcome Description:

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.

Outcome Time Frame:

21 days

Safety Issue:

No

Principal Investigator

Michael Overman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2012-0776

NCT ID:

NCT01730586

Start Date:

November 2012

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • Cancer of Gastrointestinal Tract
  • 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
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Colorectal Neoplasms
  • Gastrointestinal Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030