Colorectal CancerPhase 1NCT00336141
Vorinostat and IV Fluorouracil/Leucovorin (5FU/LV) in Patients With Metastatic Colorectal Cancer
A Phase 1 study testing Suberoylanilide hydroxamic acid in people with Colorectal Cancer, run by University of Southern California at 1 site in United States.
Trial summary
This protocol will investigate the use of vorinostat (suberoylanilide hydroxamic acid - SAHA) in combination with infusional 5-FU and leucovorin for the treatment of metastatic colorectal cancer patients who have failed standard 5FU regimens. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Suberoylanilide hydroxamic acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Apr 2009
- 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 histologically or cytologically confirmed advanced/metastatic colorectal cancer.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than 20 mm with conventional techniques or as > 10 mm with spiral CT scan.
- Patients must have received prior therapy (in any setting) with 5-FU, CPT-11, and oxaliplatin. Patients may have received prior erbitux and bevacizumab, but it is not required.
- Patients must have received at least one prior chemotherapy regimen for advanced disease.
- Tumor must be accessible for core biopsy at the beginning of treatment and patients have a high intratumoral TS expression level prior to the beginning of treatment.
- Age > 18 years. Because no dosing or AE data are currently available on the use of vorinostat in patients greater than 18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
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- Life expectancy of > 12 weeks.
- ECOG performance status 0-2 (Karnofsky > 50%; see Appendix A).
- Patients must have normal organ and marrow function as defined below:
- leukocytes > 3,000/µL
- absolute neutrophil count > 1,500/µL
- platelets > 100,000/µL
- hemoglobin > 9 mg/dL
- total bilirubin within 1.5 x normal institutional limits
- AST (SGOT)/ALT (SGPT) greater than or equal to 2.5 X institutional upper limit of normal
- creatinine greater than or equal to 1.5 X institutional upper limit of normal OR
- creatinine clearance > 60 mL/min/1.73 m2
- Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of vorinostat will be determined following review by the principal investigator. (A list of medications and substances known or with the potential to interact with selected CYP450 isoenzymes is provided in Appendix B.)
- Ability to understand and the willingness to sign a written informed consent document.
- INR is ≤ 1.5 times the upper limit of normal (ULN) unless receiving therapeutic anticoagulation
- Patient is highly unlikely to conceive as indicated by at least one "yes" answer to the following questions:
- Patient is a male and agrees to use an adequate method of contraception for the duration of the study, and for 30 days after the last dose of study medication.
- Patient is a surgically sterilized female.
- Patient is a postmenopausal female ≥ 45 years of age with > 2 years since last menses.
- Patient is a non-sterilized premenopausal female and agrees to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study and for 30 days after the last dose of study medication.
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from AEs due to agents administered more than 4 weeks earlier.
- Patients may not have received any other investigational agents within 28 days of study entry.
- Patients may not receive other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study.
- Patients with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat. These compounds include sodium butyrate, trichostatin A (TSA), trapoxin (TPX), MS-27-275 and depsipeptide.
- 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.
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- Pregnant women are excluded from this study because vorinostat is a HDAC inhibitor agent with an unknown potential for teratogenesis. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued before the mother is treated with study therapy.
- Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with vorinostat. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
- Patient is on any systemic steroids that have not been stabilized to the equivalent of ≤ 10 mg/day prednisone during the 4 weeks prior to the start of the study drugs.
- Patient has had an acute infection requiring intravenous antibiotic, antiviral, or antifungal medications within 2 weeks prior to the start of study drugs.
- Patient has an active hepatitis B or hepatitis C infection.
- Patient has a history of GI surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs.
- Patient has had prescription or non-prescription drugs or other products known to influence CYP3A4 that cannot be discontinued prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication. Refer to Appendix B for a list of commonly used moderate and potent CYP3A4 modifiers and their required washout periods.
- Patient has had prior cancer treatment with an HDAC inhibitor (e.g., Depsipeptide, MS 275, LAQ-824, PXD-101, and valproic acid). Patients who have received such agents for other indications, e.g., epilepsy, may enroll in the trial after a 30 day washout period.
Trial locations and contacts
1 site in 1 country.
United States1 site
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
About this study
Official title: Phase I/II Clinical Trial With Vorinostat and Infusional 5-FU/LV in Patients With Metastatic Colorectal Cancer Who Failed 5-FU-Based Chemotherapy
This protocol will investigate the use of vorinostat (suberoylanilide hydroxamic acid - SAHA) in combination with infusional 5-FU and leucovorin for the treatment of metastatic colorectal cancer patients who have failed standard 5FU regimens.
- Conditions
- Colorectal Cancer
- Being tested
- Suberoylanilide hydroxamic acid
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Suberoylanilide hydroxamic acidDrug
400 mg QD (every day) for five days, followed by 9 days of no vorinostat
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat | Experimental | Not described Receives: Drug: Suberoylanilide hydroxamic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity
Measured: Weekly
Secondary outcomes (1)
Response
Measured: Every 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2006 (estimated)
- Study startJun 2006
- Primary completionApr 2009
- Study completionApr 2009
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 Southern CaliforniaThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00336141
- Sponsor's protocol ID
- 3C-05-3
- Status last verified
- May 2014
- First submitted
- 9 Jun 2006
- Last updated
- 21 May 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Clinical Trial With Vorinostat and Infusional 5-FU/LV in Patients With Metastatic Colorectal Cancer Who Failed 5-FU-Based Chemotherapy
- ClinicalTrials.gov ID
- NCT00336141
- Acronym / sponsor ID
- 3C-05-3
- Conditions
- Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jun 2006
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 13 Jun 2006 (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 protocol will investigate the use of vorinostat (suberoylanilide hydroxamic acid - SAHA) in combination with infusional 5-FU and leucovorin for the treatment of metastatic colorectal cancer patients who have failed standard 5FU regimens.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat | Experimental | Drug: Suberoylanilide hydroxamic acid |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patients must have histologically or cytologically confirmed advanced/metastatic colorectal cancer.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than 20 mm with conventional techniques or as > 10 mm with spiral CT scan.
- Patients must have received prior therapy (in any setting) with 5-FU, CPT-11, and oxaliplatin. Patients may have received prior erbitux and bevacizumab, but it is not required.
- Patients must have received at least one prior chemotherapy regimen for advanced disease.
- Tumor must be accessible for core biopsy at the beginning of treatment and patients have a high intratumoral TS expression level prior to the beginning of treatment.
Key exclusion criteria (14 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from AEs due to agents administered more than 4 weeks earlier.
- Patients may not have received any other investigational agents within 28 days of study entry.
- Patients may not receive other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study.
- Patients with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat. These compounds include sodium butyrate, trichostatin A (TSA), trapoxin (TPX), MS-27-275 and depsipeptide.
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 |
|---|---|---|
| Suberoylanilide hydroxamic acid400 mg QD (every day) for five days, followed by 9 days of no vorinostat | Drug | Vorinostat |
Primary outcome
Toxicity
Time frame: Weekly
1 secondary outcome
Response
Time frame: Every 2 months
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 21 May 2014.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Suberoylanilide hydroxamic acid in people with Colorectal Cancer, run by University of Southern California 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 25 inclusion and 14 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 21 May 2014. 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?
Toxicity (time frame: Weekly). 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 21 May 2014.