Adult Solid NeoplasmPhase 1NCT01039155
Azacitidine and Oxaliplatin In Treating Patients With Advanced Cancers Relapsed or Refractory to Any Platinum Therapy
A Phase 1 study testing Azacitidine, Laboratory Biomarker Analysis and Oxaliplatin in people with Adult Solid Neoplasm and Hematopoietic and Lymphoid Cell Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm
- What is being tested?
- Azacitidine, Laboratory Biomarker Analysis and Oxaliplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Jul 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Being tested
- Azacitidine, Laboratory Biomarker Analysis, Oxaliplatin, Pharmacological Study
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
OxaliplatinDrug
Also called 1-OHP, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum
Given IV
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (azacitidine, oxaliplatin) | Experimental | 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. Receives: Drug: Azacitidine; Other: Laboratory Biomarker Analysis; Drug: Oxaliplatin; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: 28 days
Secondary outcomes (4)
Changes in concentration of oxaliplatin
Measured: Baseline to day 12
Changes in DNA methylation
Measured: Baseline to day 12
Changes in the CTR1 score
Measured: Baseline to day 28
Pharmacokinetic parameters of azacitidine and 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.
Measured: Days 1 and 5 of course 1 (azacitidine) and day 2 of course 1 (oxaliplatin)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionSep 2012
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Apostolia-Maria Tsimberidou, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01039155
- Sponsor's protocol ID
- NCI-2012-02909
- Other IDs
- NCI-2012-02909, 662917, 2008-0277, 2008-0277, 8321, P30CA016672, U01CA062461
- Status last verified
- May 2015
- First submitted
- 23 Dec 2009
- Last updated
- 6 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01039155
- Acronym / sponsor ID
- NCI-2012-02909
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2009
- Primary completion
- Sep 2012 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 24 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (azacitidine, oxaliplatin) | Experimental | Drug: Azacitidine, Other: Laboratory Biomarker Analysis, Drug: Oxaliplatin, Other: Pharmacological StudyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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%)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: 5 AZC, 5-AC, 5-Azacytidine, 5-AZCGiven IV | Drug | Treatment (azacitidine, oxaliplatin) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (azacitidine, oxaliplatin) |
| OxaliplatinAlso: 1-OHP, Dacotin, Dacplat, Diaminocyclohexane OxalatoplatinumGiven IV | Drug | Treatment (azacitidine, oxaliplatin) |
| Pharmacological StudyCorrelative studies | Other | Treatment (azacitidine, oxaliplatin) |
Primary outcome
MTD graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: 28 days
4 secondary outcomes
Changes in concentration of oxaliplatin
Time frame: Baseline to day 12
Changes in DNA methylation
Time frame: Baseline to day 12
Changes in the CTR1 score
Time frame: 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2015.
Related trials for Adult Solid Neoplasm
Recruiting
An Exploratory Study to Evaluate Immune Determinants of the Response to Adoptive Cell Therapy (ACT) in Solid and Hematologic Tumors
Solid Tumor, Adult, Solid Tumor, Childhood
Active, not recruitingPhase 1
Advanced or Recurrent Solid Tumors Treated With SHetA2
Solid Tumor, Adult
RecruitingObservational study
NCI Childhood Cancer Data Initiative (CCDI) Led Pediatric, Adolescent, and Young Adult Rare Cancer Registry for Very Rare Solid Tumors
Very Rare Tumors, Very Rare Cancers
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 1
A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
Solid Tumor, Advanced Solid Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Apostolia-Maria Tsimberidou principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azacitidine, Laboratory Biomarker Analysis and Oxaliplatin in people with Adult Solid Neoplasm and Hematopoietic and Lymphoid Cell Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2015.