Azacitidine and Oxaliplatin In Treating Patients With Advanced Cancers Relapsed or Refractory to Any Platinum Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01039155
First received: December 23, 2009
Last updated: September 16, 2014
Last verified: May 2014
  Purpose

This phase I clinical trial studies the side effects and the best dose of azacitidine and oxaliplatin in treating patients with advanced cancers that do not respond to treatment or have returned after any platinum therapy. Azacitidine is designed to activate (turn on) certain genes in cancer cells whose job is to fight tumors. Oxaliplatin is designed to block the growth and spread of new cancer cells, eventually destroying them, by damaging their deoxyribonucleic acid (DNA). Giving azacitidine with oxaliplatin may kill more cancer cells and may also reverse resistance to platinum-based drugs.


Condition Intervention Phase
Hematopoietic/Lymphoid Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: azacitidine
Drug: oxaliplatin
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of CTEP 5-Azacytidine in Combination With Oxaliplatin in Patients With Advanced Cancers Relapsed or Refractory or Refractory to Any Platinum Therapy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Changes in the CTR1 score [ Time Frame: Baseline to day 28 ] [ Designated as safety issue: No ]
  • Changes in DNA methylation [ Time Frame: Baseline to day 12 ] [ Designated as safety issue: No ]
  • Changes in concentration of oxaliplatin [ Time Frame: Baseline to day 12 ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of azacitidine and oxaliplatin [ Time Frame: Days 1 and 5 of course 1 (azacitidine) and day 2 of course 1 (oxaliplatin) ] [ Designated as safety issue: No ]
    Compartmental and non-compartmental modeling will be used to derive pharmacokinetic parameters, including maximum concentration (Cmax), time to maximum plasma concentration (Tmax), area under the curve (AUC), t ½ alpha (a), t ½ beta (B), volume of distribution (Vd), and clearance.


Enrollment: 41
Study Start Date: December 2009
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (azacitidine, oxaliplatin)
Patients receive azacitidine IV over 15-30 minutes on days 1-5 and oxaliplatin IV over 2 hours on days 2-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: azacitidine
Given IV
Other Names:
  • 5-AC
  • 5-azacytidine
  • azacytidine
  • Vidaza
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of 5-azacytidine (azacitidine) and oxaliplatin combination regimen in patients with advanced solid tumors or lymphomas relapsed or refractory to any platinum compound.

II. To define 5-azacytidine and oxaliplatin pharmacokinetics.

SECONDARY OBJECTIVES:

I. For patients treated in the expansion phase of this study: (a) to assess copper transport protein (CTR1) score; (b) to assess changes in global DNA methylation; and (c) to measure changes in oxaliplatin levels in tumor biopsies between pretreatment and day 12 of the first cycle of 5-azacytidine plus oxaliplatin therapy.

II. To correlate results of the pharmacokinetic studies of 5-azacytidine and oxaliplatin with changes in CTR1, changes in global DNA methylation and changes in oxaliplatin levels in tissue biopsies of patients treated in the expansion phase of this study.

OUTLINE: This is a dose-escalation study.

Patients receive azacitidine IV over 15-30 minutes on days 1-5 and oxaliplatin IV over 2 hours on days 2-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically confirmed malignancy (solid tumor or lymphoma) that is metastatic or unresectable and for which standard curative or palliative measures are not expected to increase survival by at least 3 months
  • Patients must have an advanced cancer relapsed or refractory to any platinum compound; platinum-refractory disease is defined as disease that does not respond to a platinum compound-containing regimen or that recurs after treatment with a platinum compound-containing regimen
  • Patients must have had >= 1 prior chemotherapy regimen; there is no maximum allowable number of prior regimens, provided all other eligibility criteria are met
  • Patients must be >= 6 weeks beyond treatment with a nitrosourea or mitomycin-C, >= 4 weeks beyond other chemotherapy or radiotherapy, and must have recovered to =< grade 1 toxicity for any treatment-limiting toxicity of prior therapy; (exception: patients may have received palliative low-dose radiotherapy to the limbs 1-4 weeks before this therapy, provided pelvis, ribs, sternum, scapulae, vertebrae, or skull were not included in the radiotherapy field)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Leukocytes >= 4,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Total bilirubin =< 1.0 mg/dL
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional upper limit of normal
  • Creatinine (serum) =< 2.0 mg/dL
  • International normalized ratio (INR) of less than or equal to 1.75 per institutional guideline
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients must have the ability to understand and the willingness to sign a written informed consent document, including consent for the required tumor biopsy (in the expansion phase), blood, and pharmacokinetics studies
  • Tumor should be accessible for repeat biopsy if in the expansion phase; biopsies will be performed in the expansion phase; the expansion cohort will be between 10 and 20 patients
  • Patients must have expected survival of at least 3 months

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered to =< grade 1 treatment-limiting toxicity levels for adverse events due to agents administered more than 4 weeks earlier; (exception: patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy, provided pelvis, ribs, sternum, scapulae, vertebrae, or skull were not included in the radiotherapy field)
  • Patients may not be receiving any other concurrent investigational agents
  • Patients must not have a history of allergic reactions attributed to 5-azacytidine, oxaliplatin, or compounds with a similar composition
  • Patients must not have oxaliplatin intolerance
  • Patients must not have uncontrolled intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, potentially life-threatening cardiac arrhythmia, and psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with 5-azacytidine
  • Patients known to be human immunodeficiency virus (HIV)-positive and receiving anti-retroviral therapy must have both a minimum of 350 CD4+ cells/mm^3 and no history of acquired immunodeficiency syndrome (AIDS) defining conditions except for lymphoma
  • Patients who have had surgery within 2 weeks prior to entering the study are not eligible
  • Patients who have been removed from prior platinum-containing therapy due to platinum-compound cumulative toxicity
  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: NCT01039155

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Apostolia-Maria Tsimberidou M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01039155     History of Changes
Other Study ID Numbers: NCI-2012-02909, NCI-2012-02909, 662917, 2008-0277, 2008-0277, 8321, U01CA062461, P30CA016672
Study First Received: December 23, 2009
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Azacitidine
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014