Immune System Diseases

All Conditions

Neoplasms

Digestive System Diseases

Hypersensitivity

Adenocarcinoma

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Bone Density Conservation Agents

Vitamins

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Calcium

Calcium, Dietary

Folinic Acid

Patients receive carbon C 14 oxaliplatin microdose IV over 120 minutes. Beginning not more than 4 weeks after the initial carbon C 14 oxaliplatin microdose administration, patients receive FOLFOX6 comprised of leucovorin calcium IV, fluorouracil IV over 2 hours (over 46-48 hours via ambulatory infusion pump on days 1 and 2), and oxaliplatin (contain carbon C 14 microdose course I only) IV over 2 hours on day 1.

Carbon C 14 Oxaliplatin

Edward Kim

This pilot clinical trial studies how well carbon C 14 oxaliplatin microdosing assay works in predicting exposure and sensitivity to oxaliplatin-based chemotherapy in patients with colorectal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Carbon C 14 is a radioactive form of carbon, exists in nature and in the body at a low level. Microdose carbon C 14 oxaliplatin diagnostic assay may help doctors understand how well patients respond to treatment and develop individualize oxaliplatin dosing in patients with colorectal cancer.

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of \[14C\] (carbon C 14) oxaliplatin microdose as a clinical assay to predict oxaliplatin exposure.

SECONDARY OBJECTIVES:

I. To estimate the degree to which a \[14C\]oxaliplatin microdose predicts the observed pharmacokinetics of standard dose oxaliplatin.

II. To validate that intrapatient variation of exposure to a \[14C\]oxaliplatin microdose is less than 5%.

III. To detect the levels of oxaliplatin-deoxyribonucleic acid (DNA) adducts induced by oxaliplatin microdosing in peripheral blood mononuclear cells (PBMCs), and correlate the results with patient response and progression free survival on oxaliplatin-based chemotherapy.

IV. To develop preliminary safety data of \[14C\]oxaliplatin microdosing for future studies.

OUTLINE:

Patients receive carbon C 14 oxaliplatin microdose intravenously (IV) over 120 minutes. Beginning not more than 4 weeks after the initial carbon C 14 oxaliplatin microdose administration, patients receive FOLFOX comprised of leucovorin calcium IV, fluorouracil IV over 2 hours (over 46-48 hours via ambulatory infusion pump on days 1 and 2), and oxaliplatin (contain carbon C 14 microdose course I only) IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Oxaliplatin Microdosing Assay in Predicting Exposure and Sensitivity to Oxaliplatin-Based Chemotherapy

Pilot Study of a Carbon 14 Oxaliplatin Microdosing Assay to Predict Exposure and Sensitivity to Oxaliplatin-Based Chemotherapy in Advanced Colorectal Cancer

Correlate area under curve from phase 0 microdosing with area under curve for therapeutic dose of oxaliplatin

Will characterize the repair of DNA adducts in PBMC, using descriptive statistics.

Assess toxicity to both microdoses of carbon C 14 oxaliplatin. Toxicities potentially related to carbon C 14 oxaliplatin will be assessed from initiation of the study to at least 14 days after the administration of the FOLFOX-integrated microdose or until full recover of toxicity (whichever is longer). Safety will be assessed through summaries of adverse events and laboratory evaluations.

Response was determined according to RECIST criteria as either partial response (PR) or one almost complete response (CR) or progressive disease (PD).

National Cancer Institute (NCI)

Principal Investigator

Incidence of Adverse Events According to the Common Terminology Criteria for Adverse Events Version 4

Patients receive carbon C 14 oxaliplatin microdose IV over 120 minutes. Beginning not more than 4 weeks after the initial carbon C 14 oxaliplatin microdose administration, patients receive FOLFOX6 comprised of leucovorin calcium IV, fluorouracil IV over 2 hours (over 46-48 hours via ambulatory infusion pump on days 1 and 2), and oxaliplatin (contain carbon C 14 microdose course I only) IV over 2 hours on day 1.

Carbon C 14 Oxaliplatin: Intravenous infusion

Oxaliplatin: Intravenous infusion

Carbon C 14 Oxaliplatin and Oxaliplatin

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Analyst

Feasibility of 14C Oxaliplatin Microdose as a Clinical Assay to Predict Oxaliplatin Exposure

Tumor measurements were not collected to assess this outcome measure.

Duration of Disease Control (DDC) According to RECIST 1.1

Anorexia

Arthralgia

Dehydration

Diarrhea

Endocrine disorders - Other - Cold sensitivity

Fatigue

Hyperkalemia

Lymphocyte count decreased

Nausea

Neutrophil count decreased

Pain in extremity

Peripheral sensory neuropathy

Vomiting

White blood cell decreased

Number of Participants With Adverse Events According to CTCAE Version 4

Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

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.

carbon C 14 oxaliplatin

oxaliplatin

laboratory biomarker analysis

Chong-Xian Pan

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.

PRIMARY OBJECTIVES:

I. 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:

I. 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.

V. 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.

Oxaliplatin in Treating Patients With Metastatic Breast Cancer

A Diagnostic Feasibility Trial of a [14C]Oxaliplatin Microdosing Assay for Prediction of Chemoresistance to Oxaliplatin Chemotherapy

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.

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.

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.

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.

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.

Will be characterized using descriptive statistics (graphical summaries, mean, SD, box plots).

Descriptive statistics, such as graphical summaries, mean, SD, box plots will be used for responders and non-responders.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Oxaliplatin Microdosing Assay in Predicting Exposure and Sensitivity to Oxaliplatin-Based Chemotherapy	NCT02569723	Colon Adenocarc...	Carbon C 14 Oxa... Oxaliplatin	18 Years -	University of California, Davis
Oxaliplatin in Treating Patients With Metastatic Breast Cancer	NCT02077998	Stage IV Breast...	carbon C 14 oxa... oxaliplatin laboratory biom...	18 Years -	University of California, Davis
Oxaliplatin Microdosing Assay in Predicting Exposure and Sensitivity to Oxaliplatin-Based Chemotherapy	NCT02569723	Colon Adenocarc...	Carbon C 14 Oxa... Oxaliplatin	18 Years -	University of California, Davis
Oxaliplatin Microdosing Assay in Predicting Exposure and Sensitivity to Oxaliplatin-Based Chemotherapy	NCT02569723	Colon Adenocarc...	Carbon C 14 Oxa... Oxaliplatin	18 Years -	University of California, Davis
Oxaliplatin in Treating Patients With Metastatic Breast Cancer	NCT02077998	Stage IV Breast...	carbon C 14 oxa... oxaliplatin laboratory biom...	18 Years -	University of California, Davis

Spots Global Cancer Trial Database for carbon c 14 oxaliplatin