Colorectal CancerPhase 1NCT00449137
Arsenic Trioxide, Fluorouracil, and Leucovorin in Treating Patients With Stage IV Colorectal Cancer That Has Relapsed or Not Responded to Treatment
A Phase 1 study testing Arsenic trioxide, Fluorouracil and Leucovorin calcium in people with Colorectal Cancer, run by University of Miami at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Arsenic trioxide may help fluorouracil and leucovorin work better by making tumor cells more sensitive to the drugs. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Arsenic trioxide, Fluorouracil and Leucovorin calcium
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Dec 2010
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed colorectal cancer
- Stage IV disease (i.e., any T, any N, M1 disease)
- Relapsed or refractory disease
- Disease progressed after ≥ 2 different fluorouracil-containing chemotherapy regimens (e.g., irinotecan hydrochloride or oxaliplatin with or without bevacizumab)
- Bidimensionally measurable disease
- Must have tumor amenable to biopsy and be willing to undergo fine-needle aspiration
- No CNS metastases
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 2 months
- Platelet count > 100,000/mm^3
- WBC ≥ 3,000/mm^3
- Creatinine ≤ 1.5 times upper limit of normal
- Bilirubin ≤ 2 times normal
- SGOT ≤ 5 times normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 4 months after completion of study treatment
- No preexisting peripheral neuropathy ≥ grade 2
- Ejection fraction ≥ 30%
- Baseline QT interval < 500 msec
- No serious underlying medical illness or active infection
- No underlying medical condition that could be aggravated by the treatment
- No life-threatening disease unrelated to colorectal cancer
- No other malignancy within the past 5 years unless currently disease-free and all therapy for the malignancy has been completed
- No preexisting neurological disorder (i.e., seizure disorder) ≥ grade 3
- No cardiac disease, including any of the following:
- Recurrent supraventricular arrhythmia
- Any type of sustained ventricular arrhythmia or conduction block (e.g., grade II or III atrioventricular block or left bundle branch block)
- Uncontrolled ischemic heart disease
- History of nonsustained ventricular tachycardia
- Prolonged PR intervals (i.e., 1st degree heart block)
- No known hypersensitivity to arsenic trioxide or fluorouracil
- No history of allergic reactions attributed to compounds of similar biologic composition to arsenic trioxide or fluorouracil
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from all treatment-related toxicity
- At least 4 weeks since prior chemotherapy or radiotherapy and recovered
- More than 4 weeks since prior investigational drug
- No other concurrent investigational or commercial anticancer agent or therapy
- Concurrent local radiotherapy allowed for symptom relief (e.g., significant onset of pain after enrollment, but before beginning study therapy)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, 33136
About this study
Official title: A Phase I Study of 5-FU (Plus Leucovorin) and Arsenic Trioxide for Patients With Refractory/Relapsed Metastatic Colorectal Carcinoma
RATIONALE: Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Arsenic trioxide may help fluorouracil and leucovorin work better by making tumor cells more sensitive to the drugs. Giving arsenic trioxide together with fluorouracil and leucovorin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide and fluorouracil when given together with leucovorin in treating patients with stage IV colorectal cancer that has relapsed or not responded to treatment.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose and best dose combination of fluorouracil and arsenic trioxide when given together with leucovorin calcium in patients with relapsed or refractory stage IV colorectal cancer.
- Determine if arsenic trioxide down regulates the expression of thymidylate synthase in tumor and in peripheral blood mononuclear cells in these patients.
OUTLINE: This is a dose-escalation study of fluorouracil and arsenic trioxide.
Patients receive arsenic trioxide IV over 1-4 hours on days 1-5, 8, 11, 15, 18, and 22 and fluorouracil IV over 24 hours and leucovorin calcium IV over 24 hours on days 8, 15, and 22. Treatment repeats every 5 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 1-6 patients receive escalating doses of fluorouracil and arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
Patients undergo peripheral blood mononuclear cell (PBMC) collection and fine-needle tumor aspiration periodically to determine the effects of arsenic trioxide on thymidylate synthase expression in the tumor and in PBMCs.
After completion of study treatment, patients are followed periodically for 3 years.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
- Conditions
- Colorectal Cancer
- Being tested
- Arsenic trioxide, Fluorouracil, Leucovorin calcium, Plasma levels of elemental arsenic, Peripheral Blood Mononuclear Cells (PBMC) for mRNA analysis
- Keywords
- recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arsenic trioxideDrug
Also called ATO
ATO will be administered at dose levels determined by the dose escalation scheme (section 4.2). Intra-venous (IV) infusion of ATO (mg/kg body weight) over 1-4 hours will be administered for 5 consecutive days (day 1 to day 5) during the first week, twice a week on weeks 2 and 3 (days 8, 11, 15, and 18), and only one day (day 22) of week 4. Treatment will continue for a maximum of 8 cycles, provided that the patient tolerates treatment and there is evidence of clinical benefit.
FluorouracilDrug
Also called 5-Fu
Escalate 5-FU, starting at dose 1600 mg/m2. On day 8, 15, and 22 the assigned dose of 5 FU plus 500 mg/m2 of leucovorin will be administered over 24 hours intravenous infusion following the administration of arsenic trioxide. Treatment will continue for a maximum of 8 cycles, provided that the patient tolerates treatment and there is evidence of clinical benefit.
On day 8, 15, and 22 the assigned dose of 5 FU plus 500 mg/m2 of leucovorin will be administered over 24 hours intravenous infusion following the administration of arsenic trioxide. Treatment will continue for a maximum of 8 cycles, provided that the patient tolerates treatment and there is evidence of clinical benefit.
Plasma levels of elemental arsenicOther
Pre-Treatment and and one hour post ATO on days 1, 5, 8, 11,15, 18, and 22
Peripheral Blood Mononuclear Cells (PBMC) for mRNA analysisGenetic
Peripheral blood samples (PAXgene Blood RNA tube, Qiagen, USA) will be obtained up to 2 weeks prior to start of treatment (same day as the first FNA) and one hour post ATO on days 1, 5, 8, 11,15, 18, and 22. Along with FNA an additional blood sample will be obtained on day 23 of every odd treatment cycle.
Tumor Biopsy (Fine-Needle Aspiration)Procedure or surgery
Also called FNA
Pre-Treatment, Day 23 of Cycles 1, 3, 5, 7
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Not described Receives: Drug: Arsenic trioxide; Drug: Fluorouracil; Drug: Leucovorin calcium; Other: Plasma levels of elemental arsenic; Genetic: Peripheral Blood Mononuclear Cells (PBMC) for mRNA analysis; Procedure: Tumor Biopsy (Fine-Needle Aspiration) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
The objective of this phase I study is to determine a phase II dose of combination of 5-FU and ATO that can be safely used for the treatment of 5-FU resistant colon cancer. Following the dose escalation/de-escalation procedure described in section 4.2, the recommended phase II dose of the combination 5-FU with ATO will be established as the maximum tolerated dose (MTD), defined as the highest dose level combination at which <=1 out of 6 patients experiencing DLT.
Measured: At study completion
Thymidylate synthase expression
We will characterize TS levels in study patients at baseline and at subsequent times following initiation of treatment by descriptive statistics (minimum, maximum, average, standard deviation)
Measured: Baseline, Subsequent times
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2007 (estimated)
- Study startJun 2005
- Primary completionFeb 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by University of MiamiThe 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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bach Ardalan, MD, Study chair, University of Miami Sylvester Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00449137
- Sponsor's protocol ID
- 20050801
- Other IDs
- SCCC-2004162
- Status last verified
- Dec 2016
- First submitted
- 15 Mar 2007
- Last updated
- 15 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of 5-FU (Plus Leucovorin) and Arsenic Trioxide for Patients With Refractory/Relapsed Metastatic Colorectal Carcinoma
- ClinicalTrials.gov ID
- NCT00449137
- Acronym / sponsor ID
- 20050801
- Conditions
- Colorectal Cancer
- Keywords
- recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- Jun 2005
- Primary completion
- Feb 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 19 Mar 2007 (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.
RATIONALE: Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Arsenic trioxide may help fluorouracil and leucovorin work better by making tumor cells more sensitive to the drugs. Giving arsenic trioxide together with fluorouracil and leucovorin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide and fluorouracil when given together with leucovorin in treating patients with stage IV colorectal cancer that has relapsed or not responded to treatment.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose and best dose combination of fluorouracil and arsenic trioxide when given together with leucovorin calcium in patients with relapsed or refractory stage IV colorectal cancer.
- Determine if arsenic trioxide down regulates the expression of thymidylate synthase in tumor and in peripheral blood mononuclear cells in these patients.
OUTLINE: This is a dose-escalation study of fluorouracil and arsenic trioxide.
Patients receive arsenic trioxide IV over 1-4 hours on days 1-5, 8, 11, 15, 18, and 22 and fluorouracil IV over 24 hours and leucovorin calcium IV over 24 hours on days 8, 15, and 22. Treatment repeats every 5 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 1-6 patients receive escalating doses of fluorouracil and arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
Patients undergo peripheral blood mononuclear cell (PBMC) collection and fine-needle tumor aspiration periodically to determine the effects of arsenic trioxide on thymidylate synthase expression in the tumor and in PBMCs.
After completion of study treatment, patients are followed periodically for 3 years.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: Arsenic trioxide, Drug: Fluorouracil, Drug: Leucovorin calcium, Other: Plasma levels of elemental arsenic, Genetic: Peripheral Blood Mononuclear Cells (PBMC) for mRNA analysis, Procedure: Tumor Biopsy (Fine-Needle Aspiration) |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Arsenic trioxideAlso: ATOATO will be administered at dose levels determined by the dose escalation scheme (section 4.2). Intra-venous (IV) infusion of ATO (mg/kg body weight) over 1-4 hours will be administered for 5 consecutive days (day 1 to day 5) during the first week, twice a week on weeks 2 and 3 (days 8, 11, 15, and 18), and only one day (day 22) of week 4. Treatment will continue for a maximum of 8 cycles, provided that the patient tolerates treatment and there is evidence of clinical benefit. | Drug | Single Arm |
| FluorouracilAlso: 5-FuEscalate 5-FU, starting at dose 1600 mg/m2. On day 8, 15, and 22 the assigned dose of 5 FU plus 500 mg/m2 of leucovorin will be administered over 24 hours intravenous infusion following the administration of arsenic trioxide. Treatment will continue for a maximum of 8 cycles, provided that the patient tolerates treatment and there is evidence of clinical benefit. | Drug | Single Arm |
| Leucovorin calciumOn day 8, 15, and 22 the assigned dose of 5 FU plus 500 mg/m2 of leucovorin will be administered over 24 hours intravenous infusion following the administration of arsenic trioxide. Treatment will continue for a maximum of 8 cycles, provided that the patient tolerates treatment and there is evidence of clinical benefit. | Drug | Single Arm |
| Plasma levels of elemental arsenicPre-Treatment and and one hour post ATO on days 1, 5, 8, 11,15, 18, and 22 | Other | Single Arm |
| Peripheral Blood Mononuclear Cells (PBMC) for mRNA analysisPeripheral blood samples (PAXgene Blood RNA tube, Qiagen, USA) will be obtained up to 2 weeks prior to start of treatment (same day as the first FNA) and one hour post ATO on days 1, 5, 8, 11,15, 18, and 22. Along with FNA an additional blood sample will be obtained on day 23 of every odd treatment cycle. | Genetic | Single Arm |
| Tumor Biopsy (Fine-Needle Aspiration)Also: FNAPre-Treatment, Day 23 of Cycles 1, 3, 5, 7 | Procedure or surgery | Single Arm |
Primary outcome
Maximum tolerated dose
Time frame: At study completion
The objective of this phase I study is to determine a phase II dose of combination of 5-FU and ATO that can be safely used for the treatment of 5-FU resistant colon cancer. Following the dose escalation/de-escalation procedure described in section 4.2, the recommended phase II dose of the combination 5-FU with ATO will be established as the maximum tolerated dose (MTD), defined as the highest dose level combination at which <=1 out of 6 patients experiencing DLT.
Thymidylate synthase expression
Time frame: Baseline, Subsequent times
We will characterize TS levels in study patients at baseline and at subsequent times following initiation of treatment by descriptive statistics (minimum, maximum, average, standard deviation)
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 15 Dec 2016.
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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.
Bach Ardalan, MD study chair
University of Miami Sylvester Comprehensive 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 Arsenic trioxide, Fluorouracil and Leucovorin calcium in people with Colorectal Cancer, run by University of Miami 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?
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 15 Dec 2016. 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?
Maximum tolerated dose (time frame: At study completion). The study lists 2 primary outcomes in all. 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 15 Dec 2016.