Stage IV Breast CancerEarly Phase 1NCT02077998
Oxaliplatin in Treating Patients With Metastatic Breast Cancer
A Early Phase 1 study testing carbon C 14 oxaliplatin, oxaliplatin and laboratory biomarker analysis in people with Stage IV Breast Cancer, run by University of California, Davis at 1 site in United States.
Trial summary
This phase 0/II trial studies the effect of carbon C 14 oxaliplatin in tumor tissue and blood and the side effects and how well oxaliplatin works in treating patients with metastatic breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IV Breast Cancer
- What is being tested?
- carbon C 14 oxaliplatin, oxaliplatin and laboratory biomarker analysis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to Dec 2015
- Phase
- Early 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
- Participants must have metastatic breast cancer that can be biopsied or resected around 48 hours after dosing with one microdose of [14C]oxaliplatin (carbon C 14 oxaliplatin)
- Prior radiation or surgery is allowed, but should be finished at least 2 weeks prior to study enrollment; if a participant has prior radiation therapy, at least one measurable lesion outside of the radiation field should be available for the evaluation of response to chemotherapy
- Patients with metastatic breast cancer for which no standard therapy exists will be recruited for this study; more specifically, for patients with hormone receptor positive/human epidermal growth factor receptor 2 (Her2) negative disease, this includes previous therapy with tamoxifen or an aromatase inhibitor and one line of chemotherapy in the metastatic setting; for patients with Her2 positive disease, this includes 2 lines of Her2 directed therapy in the metastatic setting; and for patients with triple negative disease, this includes one line of chemotherapy in the metastatic setting; once we have identified the dose of [14C]oxaliplatin, we will only recruit triple negative breast cancer patients that progressed after one line of chemotherapy in the metastatic setting
- Any number of prior therapies other than oxaliplatin is allowed
- Eastern Cooperative Oncology Group (ECOG) performance status equal to or less than 2 (Karnofsky equal to or greater than 50%)
- Life expectancy of at least 3 months
Show all 16Show fewer
- Absolute neutrophil count greater than or equal to 1,500/microL
- Platelets greater than or equal to 100,000/microL
- Total bilirubin less than 1.5 X institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) less than or equal to 2.5 X ULN
- Creatinine less than 1.5 X ULN
- No pre-existing sensory neuropathy > grade 1
- Women of child bearing potential must not be pregnant; a pre-study pregnancy test must be negative
- Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 30 days after study participation
- Men must agree to use adequate contraception (barrier method or abstinence) prior to study entry and for 30 days after study participation
- Ability to understand and willing to sign a written informed consent document
Who cannot join
- Patients must not receive concomitant radiation with chemotherapy if they do not have any measurable lesions outside of the radiation field
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Participants who are pregnant or nursing
- Participants who are allergic to platinum agent
- Participants who have more than grade 1 peripheral neuropathy
Trial locations and contacts
1 site in 1 country.
United States1 site
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: A Diagnostic Feasibility Trial of a [14C]Oxaliplatin Microdosing Assay for Prediction of Chemoresistance to Oxaliplatin Chemotherapy
This phase 0/II trial studies the effect of carbon C 14 oxaliplatin in tumor tissue and blood and the side effects and how well oxaliplatin works in treating patients with metastatic breast cancer. DNA analysis of tumor tissue and blood samples from patients receiving carbon C 14 oxaliplatin may help doctors predict how well patients will respond to treatment with oxaliplatin. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
Read the detailed description
PRIMARY OBJECTIVES:
- To detect the levels of oxaliplatin-deoxyribonucleic acid (DNA) adducts induced by oxaliplatin microdosing in tumor tissue and peripheral blood mononuclear cells (PBMC), and correlate the results with patient response to oxaliplatin-based chemotherapy.
SECONDARY OBJECTIVES:
- Evaluate the efficacy of single agent oxaliplatin treatment (130mg/m^2, 2 hr intravenously [IV] day 1; every 3 weeks) in pre-treated, metastatic breast cancer patients.
II. Evaluate the toxicity of oxaliplatin microdose and chemotherapy treatment in this patient population.
III. Determine the pharmacokinetic (PK) parameters of oxaliplatin microdosing and correlate with the PK parameters of therapeutic oxaliplatin.
IV. Determine whether the pharmacokinetics of oxaliplatin microdosing affects oxaliplatin-induced DNA damage and, therefore, patient response to chemotherapy.
- Detect repair of DNA adducts in PBMC and correlate with patient response to oxaliplatin-based chemotherapy.
VI. Correlate the adduct and patient response data to DNA repair genes, such as excision repair cross-complementing (ERCC)1 levels as measured by reverse transcriptase-polymerase chain reaction (RT-PCR).
OUTLINE:
PHASE 0: Patients receive carbon C 14 oxaliplatin IV over 2 minutes on day 1.
PHASE II: Patients receive oxaliplatin IV over 2 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for up to 6 months.
- Conditions
- Stage IV Breast Cancer
- Being tested
- carbon C 14 oxaliplatin, oxaliplatin, laboratory biomarker analysis
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carbon C 14 oxaliplatinRadiation
Also called [14C] oxaliplatin
Given IV
oxaliplatinDrug
Also called 1-OHP, Dacotin, Dacplat, Eloxatin
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Diagnostic (carbon C 14 oxaliplatin and oxaliplatin) | Experimental | PHASE 0: Patients receive carbon C 14 oxaliplatin IV over 2 minutes on day 1.
PHASE II: Patients receive oxaliplatin IV over 2 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Receives: Radiation: carbon C 14 oxaliplatin; Drug: oxaliplatin; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Threshold at which oxaliplatin-DNA adducts predict response to therapy
The concentration of oxaliplatin-DNA adducts induced will be characterized using descriptive statistics (graphical summaries, mean, standard deviation [SD], box plots) in PBMC and tumor for responders and non-responders to chemotherapy. The mean level of oxaliplatin-DNA adducts will be compared in responders to chemotherapy to that of non-responders using a 2-sample t-test at the 0.05 level (2-sided). The Youden index will be used to estimate and compute a 95% confidence interval for the optimal cut-point in oxaliplatin-DNA adduct levels to differentiate between responders and non-responders.
Measured: Up to 6 months post-treatment
Secondary outcomes (8)
Response rate assessed using Response Evaluation Criteria in Solid Tumors (RECIST)
Will be analyzed primarily with respect to their association with level of oxaliplatin-DNA adducts. The distribution of clinical endpoints, including toxicity, will be summarized using frequencies for categorical data and Kaplan-Meier curves for survival data.
Measured: Up to 6 months post-treatment
Progression-free survival
Will be analyzed primarily with respect to their association with level of oxaliplatin-DNA adducts. The distribution of clinical endpoints, including toxicity, will be summarized using frequencies for categorical data and Kaplan-Meier curves for survival data.
Measured: From the date of enrollment to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or date of death due to any cause, whichever occurs first, assessed up to 6 months post-treatment
Overall survival
Will be analyzed primarily with respect to their association with level of oxaliplatin-DNA adducts. The distribution of clinical endpoints, including toxicity, will be summarized using frequencies for categorical data and Kaplan-Meier curves for survival data.
Measured: From the first treatment to death or to the last treatment follow-up, assessed up to 6 months post-treatment
Overall toxicity from both the carbon C 14 oxaliplatin microdose and the full dose oxaliplatin chemotherapy evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Will be analyzed primarily with respect to their association with level of oxaliplatin-DNA adducts. The distribution of clinical endpoints, including toxicity, will be summarized using frequencies for categorical data and Kaplan-Meier curves for survival data. Safety will be assessed through summaries of adverse events, the frequency of treatment discontinuations due to adverse events, and laboratory evaluations. Descriptive statistics will be used rather than inferential statistics.
Measured: Up to 30 days post-treatment
PK parameters including maximum concentration (Cmax), half-life (t1/2), and area under the curve (AUC) from both micro- and therapeutic- dosing in the same patients
PK parameters from microdosing will be correlated with parameters from therapeutic dosing. Descriptive summaries (scatterplots, tables, mean, SD, correlation coefficient) of the relationship between the two sets of parameters will be presented.
Measured: Pre-dose; 5, 15, and 30 minutes; and 2, 4, 8, 24, and 48 hours
Levels of oxaliplatin-DNA adducts in tumor and PBMC
Responders and non-responders will be compared using two-sample t-tests; if the half-lives are not normally distributed, Wilcoxon rank-sum tests will be used. The effect of half-life on progression-free survival will be explored using Cox proportional hazards models. Similar analyses will be performed for other PK parameters.
Measured: Up to 48 hours
Repair of oxaliplatin-DNA monoadducts in PBMCs
Will be characterized using descriptive statistics (graphical summaries, mean, SD, box plots).
Measured: Up to 48 hours
Messenger ribonucleic acid (mRNA) expression levels of ERCC1
Descriptive statistics, such as graphical summaries, mean, SD, box plots will be used for responders and non-responders.
Measured: Up to 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2014 (estimated)
- Study startMay 2015
- Primary completionMay 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IV Breast CancerStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Chong-Xian Pan, Principal investigator, UC Davis Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02077998
- Sponsor's protocol ID
- UCDCC#237
- Other IDs
- 457404, UCDCC#237, P30CA093373, NCI-2013-01747
- Status last verified
- Jan 2018
- First submitted
- 28 Feb 2014
- Last updated
- 9 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Diagnostic Feasibility Trial of a [14C]Oxaliplatin Microdosing Assay for Prediction of Chemoresistance to Oxaliplatin Chemotherapy
- ClinicalTrials.gov ID
- NCT02077998
- Acronym / sponsor ID
- UCDCC#237
- Conditions
- Stage IV Breast Cancer
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2015
- Primary completion
- May 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 4 Mar 2014 (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 0/II trial studies the effect of carbon C 14 oxaliplatin in tumor tissue and blood and the side effects and how well oxaliplatin works in treating patients with metastatic breast cancer. DNA analysis of tumor tissue and blood samples from patients receiving carbon C 14 oxaliplatin may help doctors predict how well patients will respond to treatment with oxaliplatin. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
Detailed description
PRIMARY OBJECTIVES:
- To detect the levels of oxaliplatin-deoxyribonucleic acid (DNA) adducts induced by oxaliplatin microdosing in tumor tissue and peripheral blood mononuclear cells (PBMC), and correlate the results with patient response to oxaliplatin-based chemotherapy.
SECONDARY OBJECTIVES:
- Evaluate the efficacy of single agent oxaliplatin treatment (130mg/m^2, 2 hr intravenously [IV] day 1; every 3 weeks) in pre-treated, metastatic breast cancer patients.
II. Evaluate the toxicity of oxaliplatin microdose and chemotherapy treatment in this patient population.
III. Determine the pharmacokinetic (PK) parameters of oxaliplatin microdosing and correlate with the PK parameters of therapeutic oxaliplatin.
IV. Determine whether the pharmacokinetics of oxaliplatin microdosing affects oxaliplatin-induced DNA damage and, therefore, patient response to chemotherapy.
- Detect repair of DNA adducts in PBMC and correlate with patient response to oxaliplatin-based chemotherapy.
VI. Correlate the adduct and patient response data to DNA repair genes, such as excision repair cross-complementing (ERCC)1 levels as measured by reverse transcriptase-polymerase chain reaction (RT-PCR).
OUTLINE:
PHASE 0: Patients receive carbon C 14 oxaliplatin IV over 2 minutes on day 1.
PHASE II: Patients receive oxaliplatin IV over 2 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for up to 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Diagnostic (carbon C 14 oxaliplatin and oxaliplatin) | Experimental | Radiation: carbon C 14 oxaliplatin, Drug: oxaliplatin, Other: laboratory biomarker analysisPHASE 0: Patients receive carbon C 14 oxaliplatin IV over 2 minutes on day 1. PHASE II: Patients receive oxaliplatin IV over 2 hours on day 1. Courses repeat every 3 weeks 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)
- Participants must have metastatic breast cancer that can be biopsied or resected around 48 hours after dosing with one microdose of [14C]oxaliplatin (carbon C 14 oxaliplatin)
- Prior radiation or surgery is allowed, but should be finished at least 2 weeks prior to study enrollment; if a participant has prior radiation therapy, at least one measurable lesion outside of the radiation field should be available for the evaluation of response to chemotherapy
- Patients with metastatic breast cancer for which no standard therapy exists will be recruited for this study; more specifically, for patients with hormone receptor positive/human epidermal growth factor receptor 2 (Her2) negative disease, this includes previous therapy with tamoxifen or an aromatase inhibitor and one line of chemotherapy in the metastatic setting; for patients with Her2 positive disease, this includes 2 lines of Her2 directed therapy in the metastatic setting; and for patients with triple negative disease, this includes one line of chemotherapy in the metastatic setting; once we have identified the dose of [14C]oxaliplatin, we will only recruit triple negative breast cancer patients that progressed after one line of chemotherapy in the metastatic setting
- Any number of prior therapies other than oxaliplatin is allowed
- Eastern Cooperative Oncology Group (ECOG) performance status equal to or less than 2 (Karnofsky equal to or greater than 50%)
Key exclusion criteria (5 listed)
- Patients must not receive concomitant radiation with chemotherapy if they do not have any measurable lesions outside of the radiation field
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Participants who are pregnant or nursing
- Participants who are allergic to platinum agent
- Participants who have more than grade 1 peripheral neuropathy
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 |
|---|---|---|
| carbon C 14 oxaliplatinAlso: [14C] oxaliplatinGiven IV | Radiation | Diagnostic (carbon C 14 oxaliplatin and oxaliplatin) |
| oxaliplatinAlso: 1-OHP, Dacotin, Dacplat, EloxatinGiven IV | Drug | Diagnostic (carbon C 14 oxaliplatin and oxaliplatin) |
| laboratory biomarker analysisCorrelative studies | Other | Diagnostic (carbon C 14 oxaliplatin and oxaliplatin) |
Primary outcome
Threshold at which oxaliplatin-DNA adducts predict response to therapy
Time frame: Up to 6 months post-treatment
The concentration of oxaliplatin-DNA adducts induced will be characterized using descriptive statistics (graphical summaries, mean, standard deviation [SD], box plots) in PBMC and tumor for responders and non-responders to chemotherapy. The mean level of oxaliplatin-DNA adducts will be compared in responders to chemotherapy to that of non-responders using a 2-sample t-test at the 0.05 level (2-sided). The Youden index will be used to estimate and compute a 95% confidence interval for the optimal cut-point in oxaliplatin-DNA adduct levels to differentiate between responders and non-responders.
8 secondary outcomes
Response rate assessed using Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Up to 6 months post-treatment
Progression-free survival
Time frame: From the date of enrollment to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or date of death due to any cause, whichever occurs first, assessed up to 6 months post-treatment
Overall survival
Time frame: From the first treatment to death or to the last treatment follow-up, assessed up to 6 months post-treatment
Overall toxicity from both the carbon C 14 oxaliplatin microdose and the full dose oxaliplatin chemotherapy evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: Up to 30 days post-treatment
PK parameters including maximum concentration (Cmax), half-life (t1/2), and area under the curve (AUC) from both micro- and therapeutic- dosing in the same patients
Time frame: Pre-dose; 5, 15, and 30 minutes; and 2, 4, 8, 24, and 48 hours
Levels of oxaliplatin-DNA adducts in tumor and PBMC
Time frame: Up to 48 hours
Repair of oxaliplatin-DNA monoadducts in PBMCs
Time frame: Up to 48 hours
Messenger ribonucleic acid (mRNA) expression levels of ERCC1
Time frame: Up to 48 hours
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 9 Jan 2018.
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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.
Chong-Xian Pan principal investigator
UC Davis Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing carbon C 14 oxaliplatin, oxaliplatin and laboratory biomarker analysis in people with Stage IV Breast Cancer, run by University of California, Davis 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 5 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 9 Jan 2018. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Threshold at which oxaliplatin-DNA adducts predict response to therapy (time frame: Up to 6 months post-treatment). 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 9 Jan 2018.