Recurrent Colon CancerPhase 1NCT00084643
GTI-2040, Oxaliplatin, and Capecitabine in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer or Other Solid Tumors
A Phase 1 study testing GTI-2040, oxaliplatin and capecitabine in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of capecitabine when given together with GTI-2040 and oxaliplatin in treating patients with locally advanced or metastatic colorectal cancer or other solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IIIC Colon Cancer
- What is being tested?
- GTI-2040, oxaliplatin and capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- May 2004to Apr 2008
- 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 locally advanced or metastatic colorectal cancer that is not amenable to surgical treatment; selected patients with advanced disease in incurable cancers of other types may be considered
- Patients must have histological or cytological proof of malignancy
- Patients must have had at least one standard prior chemotherapy for locally advanced or metastatic disease with no prior oxaliplatin containing regimen; patients who relapse within 12 months of adjuvant therapy are eligible
- Karnofsky performance status of >= 60%
- Absolute neutrophil count > 1500/ul
- Platelets > 100,000/ul
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- Total bilirubin within institutional normal limits
- AST (SGOT)/ALT (SGPT) within 2.5 x institutional normal limits
- Alkaline phosphatase within 2.5x institutional normal limits
- Creatinine within institutional normal limits or a calculated creatinine clearance > 60 ml/min
- Patients should have no greater than grade 1 neuropathy (CTCAE v3.0)
- Ability to understand and the willingness to sign a written IRB approved consent document
- Measurable disease not required
- Previous chemotherapy must have been completed > 21 days before treatment on this study (> 6 weeks for mitomycin-c or nitrosoureas)
- Life expectancy of at least 12 weeks
Who cannot join
- Active or chronic hepatitis B or C
- HIV positive patients receiving antiviral therapy because of possible pharmacokinetic interactions
- Uncontrolled intercurrent illnesses including but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia
- Pregnant or nursing women are excluded due to the potential for teratogenic effects and for potential deleterious effects on the infant; woman of childbearing age and men must practice an effective form of contraception
- Patients with known brain metastasis are excluded due their poor prognosis and due to possible neurologic sequelae that could confound the evaluation of the investigational treatment
- Patients requiring anticoagulation are excluded as polyanions are known to inhibit clotting mechanisms and phosphorothioate oligonucleotide may act in a similar mechanism; patients receiving low dose prophylactic Coumadin (1 mg/day) may be included
- Medical, social, of psychological factors that would interfere with consent and follow-up
- Patients with a diagnosis of pulmonary fibrosis or a pulmonary interstitial process
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study of GTI-2040 in Combination With Oxaliplatin and Capecitabine in Patients With Advanced Metastatic Solid Tumors
This phase I trial is studying the side effects and best dose of capecitabine when given together with GTI-2040 and oxaliplatin in treating patients with locally advanced or metastatic colorectal cancer or other solid tumors. Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. GTI-2040 may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drugs. Giving GTI-2040 together with oxaliplatin and capecitabine may kill more tumor cells
Read the detailed description
PRIMARY OBJECTIVES:
- To establish the maximum tolerated (MTD) of a 21 day cycle of capecitabine given orally twice daily for 14 days in combination with oxaliplatin given intravenously on day 1 and GTI-2040 given as a continuous infusion over 14 days in patients with advanced metastatic solid tumors.
II. To describe the toxicities at each dose level studied.
SECONDARY OBJECTIVES:
- To evaluate the pharmacokinetics of GTI-2040, capecitabine, and oxaliplatin when these are given in combination.
II. To evaluate levels of ribonucleotide reductase -M2 subunit (RR-M2) mRNA levels using TaqMan RT-PCR in peripheral blood mononuclear cells and in tumor samples (when available). TRF support will be required and sought.
III. To quantitate changes in dCTP levels in peripheral blood mononuclear cells during treatment as a surrogate marker of RR inhibition. TRF support will be required and sought.
OUTLINE: This is a multicenter, dose-escalation study of capecitabine.
Patients receive GTI-2040 IV continuously on days 1-14, oral capecitabine twice daily on days 2-15, and oxaliplatin IV over 2 hours on day 2 of the first course. In all subsequent courses, capecitabine is administered on days 1-14, oxaliplatin is administered on day 1, and GTI-2040 is administered as in course 1. Courses repeat every 21 days in the absence of disease progression and unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of capecitabine 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.
- Conditions
- Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IIIC Colon Cancer, Stage IIIC Rectal Cancer, Stage IVA Colon Cancer, Stage IVA Rectal Cancer
- Being tested
- GTI-2040, oxaliplatin, capecitabine, pharmacological study, laboratory biomarker analysis
- Medical subject headings
- Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GTI-2040Biological
Given IV
oxaliplatinDrug
Also called 1-OHP, Dacotin, Dacplat, Eloxatin
Given IV
capecitabineDrug
Also called CAPE, Ro 09-1978/000, Xeloda
Given orally
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (GTI-2040, capecitabine, oxaliplatin) | Experimental | Patients receive GTI-2040 IV continuously on days 1-14, oral capecitabine twice daily on days 2-15, and oxaliplatin IV over 2 hours on day 2 of the first course. In all subsequent courses, capecitabine is administered on days 1-14, oxaliplatin is administered on day 1, and GTI-2040 is administered as in course 1. Courses repeat every 21 days in the absence of disease progression and unacceptable toxicity. Receives: Biological: GTI-2040; Drug: oxaliplatin; Drug: capecitabine; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of the combination of GTI-2040, oxaliplatin and capecitabine based on the incidence of dose-limiting toxicity (DLT) as assessed by CTCAE version 3.0
Adverse events will be summarized by grade, attribution, and organ system. Hematological and clinical chemistry laboratory results will be included in the adverse event summary.
Measured: 21 days
Secondary outcomes (3)
Objective response (confirmed PR and CR) according to RECIST
Calculated with exact binomial 95% confidence interval.
Measured: At 6 weeks
Pharmacokinetics
Peak and integrated blood levels will be summarized by dose level, and displayed in scatterplots with RR-M2 mRNA levels and changes.
Measured: At baseline, and at 7 and 14 days after the start of infusion
Change in biochemical and molecular correlates
Molecular correlates will be analyzed descriptively in relation to clinical outcome. The association with progression-free survival or overall survival will be assessed by dichotomizing the measures of gene expression at the median (or by previously-established cut-points) and constructing Kaplan-Meier plots.
Measured: From baseline to up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2004 (estimated)
- Study startMay 2004
- Primary completionApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Colon CancerStudies 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Stephen Shibata, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00084643
- Sponsor's protocol ID
- NCI-2012-03077
- Other IDs
- PHI-41, U01CA062505, CDR0000365466
- Status last verified
- Jan 2013
- First submitted
- 10 Jun 2004
- Last updated
- 27 Mar 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of GTI-2040 in Combination With Oxaliplatin and Capecitabine in Patients With Advanced Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT00084643
- Acronym / sponsor ID
- NCI-2012-03077
- Conditions
- Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IIIC Colon Cancer, Stage IIIC Rectal Cancer, Stage IVA Colon Cancer, Stage IVA Rectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 2004
- Primary completion
- Apr 2008 (actual)
- First posted
- 11 Jun 2004 (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 trial is studying the side effects and best dose of capecitabine when given together with GTI-2040 and oxaliplatin in treating patients with locally advanced or metastatic colorectal cancer or other solid tumors. Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. GTI-2040 may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drugs. Giving GTI-2040 together with oxaliplatin and capecitabine may kill more tumor cells
Detailed description
PRIMARY OBJECTIVES:
- To establish the maximum tolerated (MTD) of a 21 day cycle of capecitabine given orally twice daily for 14 days in combination with oxaliplatin given intravenously on day 1 and GTI-2040 given as a continuous infusion over 14 days in patients with advanced metastatic solid tumors.
II. To describe the toxicities at each dose level studied.
SECONDARY OBJECTIVES:
- To evaluate the pharmacokinetics of GTI-2040, capecitabine, and oxaliplatin when these are given in combination.
II. To evaluate levels of ribonucleotide reductase -M2 subunit (RR-M2) mRNA levels using TaqMan RT-PCR in peripheral blood mononuclear cells and in tumor samples (when available). TRF support will be required and sought.
III. To quantitate changes in dCTP levels in peripheral blood mononuclear cells during treatment as a surrogate marker of RR inhibition. TRF support will be required and sought.
OUTLINE: This is a multicenter, dose-escalation study of capecitabine.
Patients receive GTI-2040 IV continuously on days 1-14, oral capecitabine twice daily on days 2-15, and oxaliplatin IV over 2 hours on day 2 of the first course. In all subsequent courses, capecitabine is administered on days 1-14, oxaliplatin is administered on day 1, and GTI-2040 is administered as in course 1. Courses repeat every 21 days in the absence of disease progression and unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of capecitabine 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (GTI-2040, capecitabine, oxaliplatin) | Experimental | Biological: GTI-2040, Drug: oxaliplatin, Drug: capecitabine, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive GTI-2040 IV continuously on days 1-14, oral capecitabine twice daily on days 2-15, and oxaliplatin IV over 2 hours on day 2 of the first course. In all subsequent courses, capecitabine is administered on days 1-14, oxaliplatin is administered on day 1, and GTI-2040 is administered as in course 1. Courses repeat every 21 days in the absence of disease progression and unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have locally advanced or metastatic colorectal cancer that is not amenable to surgical treatment; selected patients with advanced disease in incurable cancers of other types may be considered
- Patients must have histological or cytological proof of malignancy
- Patients must have had at least one standard prior chemotherapy for locally advanced or metastatic disease with no prior oxaliplatin containing regimen; patients who relapse within 12 months of adjuvant therapy are eligible
- Karnofsky performance status of >= 60%
- Absolute neutrophil count > 1500/ul
Key exclusion criteria (8 listed)
- Active or chronic hepatitis B or C
- HIV positive patients receiving antiviral therapy because of possible pharmacokinetic interactions
- Uncontrolled intercurrent illnesses including but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia
- Pregnant or nursing women are excluded due to the potential for teratogenic effects and for potential deleterious effects on the infant; woman of childbearing age and men must practice an effective form of contraception
- Patients with known brain metastasis are excluded due their poor prognosis and due to possible neurologic sequelae that could confound the evaluation of the investigational treatment
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 |
|---|---|---|
| GTI-2040Given IV | Biological | Treatment (GTI-2040, capecitabine, oxaliplatin) |
| oxaliplatinAlso: 1-OHP, Dacotin, Dacplat, EloxatinGiven IV | Drug | Treatment (GTI-2040, capecitabine, oxaliplatin) |
| capecitabineAlso: CAPE, Ro 09-1978/000, XelodaGiven orally | Drug | Treatment (GTI-2040, capecitabine, oxaliplatin) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (GTI-2040, capecitabine, oxaliplatin) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (GTI-2040, capecitabine, oxaliplatin) |
Primary outcome
MTD of the combination of GTI-2040, oxaliplatin and capecitabine based on the incidence of dose-limiting toxicity (DLT) as assessed by CTCAE version 3.0
Time frame: 21 days
Adverse events will be summarized by grade, attribution, and organ system. Hematological and clinical chemistry laboratory results will be included in the adverse event summary.
3 secondary outcomes
Objective response (confirmed PR and CR) according to RECIST
Time frame: At 6 weeks
Pharmacokinetics
Time frame: At baseline, and at 7 and 14 days after the start of infusion
Change in biochemical and molecular correlates
Time frame: From baseline to up to 4 years
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 27 Mar 2013.
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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.
Stephen Shibata principal investigator
City of Hope Medical 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 GTI-2040, oxaliplatin and capecitabine in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, 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 15 inclusion and 8 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 27 Mar 2013. 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 of the combination of GTI-2040, oxaliplatin and capecitabine based on the incidence of dose-limiting toxicity (DLT) as assessed by CTCAE version 3.0 (time frame: 21 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 27 Mar 2013.