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

• Sponsor: Edward Kim (Other)
• Overall Status: Completed
• CT.gov ID: NCT02569723
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 53.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colon Adenocarcinoma	Drug: Carbon C 14 Oxaliplatin; Drug: Oxaliplatin	N/A

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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

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

3. 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.

4. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of a Carbon 14 Oxaliplatin Microdosing Assay to Predict Exposure and Sensitivity to Oxaliplatin-Based Chemotherapy in Advanced Colorectal Cancer
• Actual Study Start Date: Oct 16, 2015
• Actual Primary Completion Date: Apr 20, 2018
• Actual Study Completion Date: Apr 4, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: carbon C 14 oxaliplatin and oxaliplatin 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.

Drug: Carbon C 14 Oxaliplatin; Intravenous infusion; Other Names: [14C] Oxaliplatin ; Drug: Oxaliplatin; Intravenous infusion; Other Names: Eloxatin

Outcome Measures

Primary Outcome Measures

1. Feasibility of 14C Oxaliplatin Microdose as a Clinical Assay to Predict Oxaliplatin Exposure [0-5 minutes predose, 5, 15, and 30 minutes, and at 1, 2, 4, 8, and 24 hours after carbon C 14 oxaliplatin microdose]

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

Secondary Outcome Measures

1. Duration of Disease Control (DDC) According to RECIST 1.1 [Up to 2 years]

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

2. Number of Participants With Adverse Events According to CTCAE Version 4 [Approximately 2 months]

   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.

3. Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [Up to 2 years]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced or metastatic colon or rectal adenocarcinoma

• Intent to treat the patient with a leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy regimen containing fluorouracil (5-FU), leucovorin, and oxaliplatin according to clinical standard practice; the intent should be to dose oxaliplatin at 85 mg/m^2 on an every 2 week basis

• Treatment with any additional Food and Drug Administration (FDA)-approved biologic agent (i.e. bevacizumab, cetuximab, or panitumumab) is allowed according to standard practice

• 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

• Any number of prior therapies other than oxaliplatin is allowed

• Zubrod performance status equal to or less than 2 (Karnofsky equal to or greater than 50%)

• Life expectancy of at least 3 months

• Absolute neutrophil count greater than or equal to 1,500/microL

• Platelets greater than or equal to 100,000/microL

• Total bilirubin less than 3 x institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase) less than or equal to 5 x ULN

• Creatinine less than 1.5 x ULN

• 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

Exclusion Criteria:

• Prior treatment with oxaliplatin

• Patients must not receive concomitant radiation

• 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 any platinum agent

• Participants who have more than grade 1 peripheral neuropathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817

Sponsors and Collaborators

• Edward Kim
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Edward Kim, University of California, Davis

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 14, 2017
• Informed Consent Form - Nov 15, 2017

More Information

Publications

None provided.

• Responsible Party: Edward Kim, Principal Investigator, University of California, Davis
• ClinicalTrials.gov Identifier: NCT02569723
• Other Study ID Numbers: 736253; UCDCC#255; P30CA093373; UCDCC#255
• First Posted: Oct 7, 2015
• Last Update Posted: Mar 30, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Adenocarcinoma; Oxaliplatin

Study Results

Participant Flow

Arm/Group Title	Carbon C 14 Oxaliplatin and Oxaliplatin
Arm/Group Description	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
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Carbon C 14 Oxaliplatin and Oxaliplatin
Arm/Group Description	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
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 33.3%
>=65 years	4 66.7%
Sex: Female, Male (Count of Participants)
Female	4 66.7%
Male	2 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 33.3%
Not Hispanic or Latino	4 66.7%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Feasibility of 14C Oxaliplatin Microdose as a Clinical Assay to Predict Oxaliplatin Exposure
Description	Correlate area under curve from phase 0 microdosing with area under curve for therapeutic dose of oxaliplatin
Time Frame	0-5 minutes predose, 5, 15, and 30 minutes, and at 1, 2, 4, 8, and 24 hours after carbon C 14 oxaliplatin microdose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carbon C 14 Oxaliplatin and Oxaliplatin
Arm/Group Description	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
Measure Participants	6
Number [R squared]	0.63

2. Secondary Outcome

Title	Duration of Disease Control (DDC) According to RECIST 1.1
Description	Will characterize the repair of DNA adducts in PBMC, using descriptive statistics.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Tumor measurements were not collected to assess this outcome measure.

Arm/Group Title	Carbon C 14 Oxaliplatin and Oxaliplatin
Arm/Group Description	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
Measure Participants	0

3. Secondary Outcome

Title	Number of Participants With Adverse Events According to CTCAE Version 4
Description	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.
Time Frame	Approximately 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carbon C 14 Oxaliplatin and Oxaliplatin
Arm/Group Description	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
Measure Participants	6
Anorexia	1 16.7%
Arthralgia	1 16.7%
Dehydration	1 16.7%
Diarrhea	2 33.3%
Endocrine disorders - Other - Cold sensitivity	1 16.7%
Fatigue	3 50%
Hyperkalemia	1 16.7%
Lymphocyte count decreased	2 33.3%
Nausea	3 50%
Neutrophil count decreased	1 16.7%
Pain in extremity	1 16.7%
Peripheral sensory neuropathy	1 16.7%
Vomiting	1 16.7%
White blood cell decreased	1 16.7%

4. Secondary Outcome

Title	Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Description	Response was determined according to RECIST criteria as either partial response (PR) or one almost complete response (CR) or progressive disease (PD).
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Tumor measurements were not collected to assess this outcome measure.

Arm/Group Title	Carbon C 14 Oxaliplatin and Oxaliplatin
Arm/Group Description	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
Measure Participants	0

Adverse Events

Time Frame	Up to 2 years
Adverse Event Reporting Description	Incidence of Adverse Events According to the Common Terminology Criteria for Adverse Events Version 4
Arm/Group Title	Carbon C 14 Oxaliplatin and Oxaliplatin
Arm/Group Description	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
All Cause Mortality
	Carbon C 14 Oxaliplatin and Oxaliplatin
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Serious Adverse Events
	Carbon C 14 Oxaliplatin and Oxaliplatin
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Carbon C 14 Oxaliplatin and Oxaliplatin
	Affected / at Risk (%)	# Events
Total	3/6 (50%)
Endocrine disorders
Endocrine disorders - Other - Cold sensitivity	1/6 (16.7%)
Gastrointestinal disorders
Diarrhea	2/6 (33.3%)
Nausea	3/6 (50%)
Vomiting	1/6 (16.7%)
General disorders
Fatigue	3/6 (50%)
Investigations
Lymphocyte count decreased	2/6 (33.3%)
Neutrophil count decreased	1/6 (16.7%)
White blood cell decreased	1/6 (16.7%)
Metabolism and nutrition disorders
Anorexia	1/6 (16.7%)
Dehydration	1/6 (16.7%)
Hyperkalemia	1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/6 (16.7%)
Pain in extremity	1/6 (16.7%)
Nervous system disorders
Peripheral sensory neuropathy	1/6 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.