- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01039155
Azacitidine and Oxaliplatin In Treating Patients With Advanced Cancers Relapsed or Refractory to Any Platinum Therapy
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
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Correlative studies
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
MTD graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame: 28 days
|
28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in concentration of oxaliplatin
Time Frame: Baseline to day 12
|
Baseline to day 12
|
|
Changes in DNA methylation
Time Frame: Baseline to day 12
|
Baseline to day 12
|
|
Changes in the CTR1 score
Time Frame: Baseline to day 28
|
Baseline to day 28
|
|
Pharmacokinetic parameters of azacitidine and oxaliplatin
Time Frame: Days 1 and 5 of course 1 (azacitidine) and day 2 of course 1 (oxaliplatin)
|
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.
|
Days 1 and 5 of course 1 (azacitidine) and day 2 of course 1 (oxaliplatin)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Apostolia-Maria Tsimberidou, M.D. Anderson Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NCI-2012-02909 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA016672 (U.S. NIH Grant/Contract)
- U01CA062461 (U.S. NIH Grant/Contract)
- 8321 (CTEP)
- 662917
- 2008-0277 (Other Identifier: M D Anderson Cancer Center)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hematopoietic and Lymphoid Cell Neoplasm
-
University of California, San FranciscoLazarex Cancer FoundationTerminatedHematopoietic and Lymphoid Cell Neoplasm | Malignant NeoplasmUnited States
-
Douglas JohnsonIncyte CorporationRecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)RecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States, Australia, Canada
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States
-
M.D. Anderson Cancer CenterRecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States
-
M.D. Anderson Cancer CenterRecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States
-
Thomas Jefferson UniversityWithdrawnHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States
-
Mayo ClinicNational Cancer Institute (NCI)Active, not recruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States
Clinical Trials on Laboratory Biomarker Analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)Recruiting
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingLynch Syndrome | Recurrent Uterine Corpus Carcinoma | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingRecurrent Uterine Corpus Carcinoma | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
National Cancer Institute (NCI)Active, not recruitingMalignant NeoplasmUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingLung Cancer | Radiation Toxicity | Adult Brain TumorUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Askin TumorUnited States, Canada, Puerto Rico, Australia, New Zealand, Switzerland
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed