Azacitidine and CAPOX in Metastatic Colorectal Cancer

NCT01193517 | Completed Phase 1 Results

• 2 other identifiers: 2009-0625NCI-2010-01973
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Azacitidine, and Capecitabine and Oxaliplatin (CAPOX)

  Dose just below the one at which ≥ 1/3 of subjects experience a dose limiting toxicity (DLT) considered the MTD.

  Up to 3 weeks from the first dose

Secondary Outcomes (1)

• Response Rate of Azacitidine, and Capecitabine and Oxaliplatin (CAPOX)

  After 9 weeks (three, 21 day cycles)

Study Arms (2)

Phase I

EXPERIMENTAL

Dose Escalation of Azacitidine + CAPOX (Capecitabine, Oxaliplatin)

Drug: Azacitidine; Drug: Capecitabine; Drug: Oxaliplatin

Phase II

EXPERIMENTAL

MTD of Azacitidine + CAPOX

Drug: Capecitabine; Drug: Oxaliplatin; Drug: Azacitidine MTD

Interventions

Azacitidine DRUG

Starting dose level 75 mg/m2/day subcutaneously on Days 1-5 of a 21 day cycle.

Also known as: 5-Azacytidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816

Phase I

Capecitabine DRUG

1500 mg/m2/day by mouth twice daily in divided doses on Days 1-14 of a 21 day cycle.

Also known as: Xeloda

Phase I; Phase II

Oxaliplatin DRUG

Starting dose level 90 mg/m2 by vein on Day 2 of a 21 day cycle.

Also known as: Eloxatin

Phase I; Phase II

Azacitidine MTD DRUG

Highest tolerable dose of combination azacitidine with CAPOX found in Phase I.

Also known as: 5-Azacytidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816

Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• 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.
• Serum bilirubin levels \</= 1.5 times the upper limit of the normal range for the laboratory (ULN)
• Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) levels \</= 2.5 x ULN and \</= 5 x ULN in patients with liver metastases
• Serum creatinine levels \</= 1.5 x ULN
• Absolute neutrophil count of \>/=1,500/mm\^3 (ie, \>/=1.5 x 10\^9/L by International Units \[IU\]).
• Platelet count \>/=100,000/mm\^3 (IU: ≥100 x 10\^9/L).
• Hemoglobin value of \>/=9.0 g/dL.
• No limit to number of prior therapies.
• 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.
• 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.
• 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
• Phase II: Patient must be known to have CpG island methylator phenotype.

You may not qualify if:

• Patients with known brain metastases or carcinomatous meningitis
• Patients unable to swallow oral medications or with gastrointestinal disorders that might interfere with proper absorption of oral drugs.
• Known dihydropyrimidine (DPD) deficiency
• Grade 3 or more peripheral neuropathy
• 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.
• Known or suspected hypersensitivity to azacitidine or mannitol
• Pregnant or breast feeding
• 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 international normalized ratio (INR) monitoring is recommended.
• Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celgene: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Azacitidine; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Deoxycytidine; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Coordination Complexes

Results Point of Contact

• Title: Dr. Michael J Overman/ Professor, GI Medical Oncology
• Organization: UT MD Anderson Cancer Center

moverman@mdanderson.org

713-792-2828

Study Officials

• Michael Overman, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2010
• First Posted: September 2, 2010
• Study Start: August 1, 2010
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: April 15, 2020
• Results First Posted: April 15, 2020

Record last verified: 2020-04

Locations

US (1)