Azacitidine and CAPOX in Metastatic Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01193517
First received: August 31, 2010
Last updated: August 8, 2013
Last verified: August 2013
  Purpose

The goal of the Phase I portion of this study is to find the highest tolerable dose of azacitidine combined with capecitabine and oxaliplatin (CAPOX) that can be given to patients with metastatic colorectal cancer.

The goal of the Phase II portion of this study is to learn if azacitidine, given in combination with CAPOX, can help to control metastatic colorectal cancer. The safety of this drug combination will also be studied.


Condition Intervention Phase
Colorectal Cancer
Drug: Azacitidine
Drug: Capecitabine
Drug: Oxaliplatin
Drug: Azacitidine MTD
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Azacitidine and CAPOX (Capecitabine + Oxaliplatin) in Metastatic Colorectal Cancer Patients Enriched for Hypermethylation of CpG Promoter Islands

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Azacitidine, and Capecitabine and Oxaliplatin (CAPOX) [ Time Frame: Each first cycle (3 weeks) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 54
Study Start Date: August 2010
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I
Dose Escalation of Azacitidine + CAPOX (Capecitabine, Oxaliplatin)
Drug: Azacitidine
Starting dose level 75 mg/m2/day subcutaneously on Days 1-5 of a 21 day cycle.
Other Names:
  • 5-Azacytidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816
Drug: Capecitabine
1500 mg/m2/day by mouth twice daily in divided doses on Days 1-14 of a 21 day cycle.
Other Name: Xeloda
Drug: Oxaliplatin
Starting dose level 90 mg/m2 by vein on Day 2 of a 21 day cycle.
Other Name: Eloxatin
Experimental: Phase II
MTD of Azacitidine + CAPOX
Drug: Capecitabine
1500 mg/m2/day by mouth twice daily in divided doses on Days 1-14 of a 21 day cycle.
Other Name: Xeloda
Drug: Oxaliplatin
Starting dose level 90 mg/m2 by vein on Day 2 of a 21 day cycle.
Other Name: Eloxatin
Drug: Azacitidine MTD
Highest tolerable dose of combination azacitidine with CAPOX found in Phase I.
Other Names:
  • 5-Azacytidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816

  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. Phase I: Patient must have histologically or cytologically confirmed colorectal adenocarcinoma with metastatic disease documented on diagnostic imaging studies. Disease may be measurable or non-measurable as per RECIST version 1.1.
  2. ECOG performance status 0-2
  3. For patients on full-dose low-molecular weight anticoagulation, no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or know varices) is allowed.
  4. Serum bilirubin levels </= 1.5 times the upper limit of the normal range for the laboratory (ULN)
  5. Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) levels </= 2.5 x ULN and </= 5 x ULN in patients with liver metastases
  6. Serum creatinine levels </= 1.5 x ULN
  7. Absolute neutrophil count of >/=1,500/mm^3 (ie, >/=1.5 x 10^9/L by International Units [IU]).
  8. Platelet count >/=100,000/mm^3 (IU: ≥100 x 10^9/L).
  9. Hemoglobin value of >/=9.0 g/dL.
  10. No limit to number of prior therapies.
  11. Women of childbearing potential must have a negative serum pregnancy test and must be advised to avoid becoming pregnant. Men should be advised to not father a child while receiving treatment. Sexually active women of childbearing potential and men must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized.
  12. Patient must be refractory to treatment with 5-FU (either intravenous 5-FU or as the oral prodrug, capecitabine) and oxaliplatin, defined as previous clinical or radiographic progression on or within 3 months of treatment with 5-FU and oxaliplatin. There is no limit to the number of prior lines of therapy.
  13. Phase II: Patient must have histologically or cytologically confirmed colorectal adenocarcinoma with measurable metastatic disease documented on diagnostic imaging studies by RECIST version 1.1 criteria
  14. Phase II: Patient must be known to have CpG island methylator phenotype.

Exclusion Criteria:

  1. Patients with known brain metastases or carcinomatous meningitis
  2. Patients unable to swallow oral medications or with gastrointestinal disorders that might interfere with proper absorption of oral drugs.
  3. Known dihydropyrimidine (DPD) deficiency
  4. Grade 3 or more peripheral neuropathy
  5. 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.
  6. 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.
  7. Known or suspected hypersensitivity to azacitidine or mannitol
  8. Pregnant or breast feeding
  9. Because of the interaction between coumadin and capecitabine patients taking therapeutic doses of coumarin-derivative anticoagulants, are not eligible. Low-dose Coumadin (e.g. 1 mg PO per day) in patients with in-dwelling venous access devices is allowed but increased frequency of INR monitoring is recommended.
  10. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
  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: NCT01193517

Locations
United States, Texas
UT MD Anderson Cancer Center
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: NCT01193517     History of Changes
Other Study ID Numbers: 2009-0625
Study First Received: August 31, 2010
Last Updated: August 8, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Refractory metastatic colorectal cancer
CRC
colorectal adenocarcinoma with metastatic disease
Azacitidine
5-Azacytidine
5-aza
Vidaza
5-AZC
AZA-CR
Ladakamycin
NSC-102816
Capecitabine
Oxaliplatin
CAPOX
Xeloda
Eloxatin
Hypermethylation
CpG island methylator phenotype

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Azacitidine
Capecitabine
Fluorouracil
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2014