Adenocarcinoma of the ColonPhase 2NCT00942266
Vorinostat, Fluorouracil, and Leucovorin Calcium in Treating Patients With Metastatic Colorectal Cancer That Has Not Responded to Previous Treatment
A Phase 2 study testing fluorouracil, leucovorin calcium and vorinostat in people with Adenocarcinoma of the Colon and Adenocarcinoma of the Rectum, run by Roswell Park Cancer Institute at 1 site in United States.
Trial summary
RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer
- What is being tested?
- fluorouracil, leucovorin calcium and vorinostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2009to Dec 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 colorectal adenocarcinoma that is metastatic and which has failed standard treatment or for which no standard treatment is available
- Patients should have fluoropyrimidine-refractory disease; radiographic evidence of progression within 4 weeks from the last dose of a fluoropyrimidine-based regimen (at least 6 weeks of fluoropyrimidine-based treatment)
- Patients should have received and progressed on (or proved to be intolerant to) oxaliplatin and irinotecan; progression within 6 months from oxaliplatin-based therapy or irinotecan-based therapy is acceptable for eligibility
- Patients with KRAS wild-type or unknown KRAS status tumors should have progressed on or within 6 months from last cetuximab or panitumumab-based therapy; no prior cetuximab therapy is required for KRAS mutant tumors
- ECOG performance status =< 2
- Life expectancy >= 12 weeks
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- Ability to understand and the willingness to sign a written informed consent document
- Ability to swallow pills
- Absolute neutrophil count >= 1,500/uL
- Platelets >= 100,000/uL
- Total bilirubin =< institutional upper limit of normal
- AST(SGOT)/ALT(SGPT) =< 3 x institutional upper limit of normal in the absence of metastatic disease to the liver and =< 5 x institutional upper limit of normal in the setting of metastatic disease to the liver
- Creatinine =< 1.5 x institutional upper limit of normal
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- Males undergoing study treatment should also agree to adequate measures of contraception (partner contraception and use of condoms or abstinence, or vasectomy)
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from significant adverse events due to agents administered more than 3 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other agents used in study
- Greater than Grade 2 neuropathy as defined by CTCAE version 3.0
- 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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- Baseline EKG with QTc prolongation that is grade 2 or higher by CTCAE version 3.0
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with vorinostat
- Patients should not have taken valproic acid or other histone deacetylase inhibitors, for at least 4 weeks prior to enrollment
- Patients with known HIV infection or known active viral hepatitis
- Prior treatment with vorinostat
- Other non-study medications known to increase the QTc interval
Trial locations and contacts
1 site in 1 country.
United States1 site
Roswell Park Cancer Institute
Buffalo, New York, 14263
About this study
Official title: A Randomized Phase II Study of Two Dose-Levels of Vorinostat in Combination With 5-FU and Leucovorin in Patients With Refractory Metastatic Colorectal Cancer
RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which dose of vorinostat is more effective when given together with combination chemotherapy in treating patients with metastatic colorectal cancer. PURPOSE: This randomized phase II trial is studying the best dose of vorinostat to see how well it works when given together with fluorouracil and leucovorin calcium in treating patients with metastatic colorectal cancer that has not responded to previous treatment.
Read the detailed description
PRIMARY OBJECTIVES: I. Describe the 2-months progression free rate on vorinostat 800mg/day x 3 in combination with 5-FU/L V every 2 weeks. (Arm I) II. Describe the 2-months progression free rate on vorinostat 1400mg/day x 3 in combination with 5-FU/L V every 2 weeks. (Arm II) SECONDARY OBJECTIVES: I. Describe the response rate on Arm 1 and Arm 2 of the study. II. Estimate the median progression free survival on both arms of the study. III. Describe the overall survival on Arm 1 and Arm 2 of the study. IV. Describe the toxicities on Arm 1 and Arm 2 of the study. V. Describe vorinostat pharmacokinetics on Arm 1 and Arm 2 of the study. VI. Describe 5-FU steady state pharmacokinetics on Arm 1 and Arm 2 of the study. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive low-dose oral vorinostat once daily on days 1-3, leucovorin calcium IV over 2 hours on day 2, and fluorouracil IV over 46 hours on days 2 and 3. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive high-dose oral vorinostat once daily on days 1-3 and leucovorin calcium and fluorouracil as in arm I. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up for 30 days and then every 3 months.
- Conditions
- Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer
- Being tested
- fluorouracil, leucovorin calcium, vorinostat, pharmacological study
- 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.
fluorouracilDrug
Also called 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil
Given IV
Also called calcium folinate, CF, CFR, citrovorum factor
Given IV
vorinostatDrug
Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Given orally
Also called pharmacological studies
Correlative study
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive low-dose oral vorinostat once daily on days 1-3, leucovorin calcium IV over 2 hours on day 2, and fluorouracil IV over 46 hours on days 2 and 3. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: fluorouracil; Drug: leucovorin calcium; Drug: vorinostat; Other: pharmacological study |
| Arm II | Experimental | Patients receive high-dose oral vorinostat once daily on days 1-3 and leucovorin calcium and fluorouracil as in arm I. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: fluorouracil; Drug: leucovorin calcium; Drug: vorinostat; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Control Rate (Stable Disease or Objective Response)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:
Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: At 2 months
Secondary outcomes (6)
Median Progression-free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Every 8 weeks, up to 100 weeks.
Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:
Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Every 8 weeks; up to 100 weeks.
Toxicity
Number of participants with an adverse event.
Please refer to the adverse event reporting for more detail.
Measured: Daily
Overall Survival
Measured: Every 12 weeks
Vorinostat Pharmacokinetics
Blood samples (5 ml of blood each) will be collected in red-top vacutainers (no anticoagulant) at 0 (pre- vorinostat), 0.5, 1, 2, 3, 4, 6, and 8 hours after the vorinostat dose on the first day of 5-FU infusion on cycle 1 (day 2 of cycle 1). Mean area under the curve is presented with 95% CI.
Measured: day 2 (cycle 1)
Fluorouracil Steady-state Pharmacokinetics
Blood samples will be collected for determination of plasma 5-FU steady state concentration at 6 hours after start of 5-FU continuous infusion. The mean per treatment arm are presented.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2009 (estimated)
- Study startJul 2009
- Primary completionMay 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adenocarcinoma of the ColonStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Wen Wee MA, MD, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00942266
- Sponsor's protocol ID
- I 142808
- Other IDs
- NCI-2009-01523
- Status last verified
- May 2014
- First submitted
- 17 Jul 2009
- Last updated
- 23 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Two Dose-Levels of Vorinostat in Combination With 5-FU and Leucovorin in Patients With Refractory Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00942266
- Acronym / sponsor ID
- I 142808
- Conditions
- Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jul 2009
- Primary completion
- May 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 20 Jul 2009 (estimated)
- Results
- Posted 23 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which dose of vorinostat is more effective when given together with combination chemotherapy in treating patients with metastatic colorectal cancer. PURPOSE: This randomized phase II trial is studying the best dose of vorinostat to see how well it works when given together with fluorouracil and leucovorin calcium in treating patients with metastatic colorectal cancer that has not responded to previous treatment.
Detailed description
PRIMARY OBJECTIVES: I. Describe the 2-months progression free rate on vorinostat 800mg/day x 3 in combination with 5-FU/L V every 2 weeks. (Arm I) II. Describe the 2-months progression free rate on vorinostat 1400mg/day x 3 in combination with 5-FU/L V every 2 weeks. (Arm II) SECONDARY OBJECTIVES: I. Describe the response rate on Arm 1 and Arm 2 of the study. II. Estimate the median progression free survival on both arms of the study. III. Describe the overall survival on Arm 1 and Arm 2 of the study. IV. Describe the toxicities on Arm 1 and Arm 2 of the study. V. Describe vorinostat pharmacokinetics on Arm 1 and Arm 2 of the study. VI. Describe 5-FU steady state pharmacokinetics on Arm 1 and Arm 2 of the study. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive low-dose oral vorinostat once daily on days 1-3, leucovorin calcium IV over 2 hours on day 2, and fluorouracil IV over 46 hours on days 2 and 3. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive high-dose oral vorinostat once daily on days 1-3 and leucovorin calcium and fluorouracil as in arm I. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up for 30 days and then every 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: fluorouracil, Drug: leucovorin calcium, Drug: vorinostat, Other: pharmacological studyPatients receive low-dose oral vorinostat once daily on days 1-3, leucovorin calcium IV over 2 hours on day 2, and fluorouracil IV over 46 hours on days 2 and 3. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. |
| Arm II | Experimental | Drug: fluorouracil, Drug: leucovorin calcium, Drug: vorinostat, Other: pharmacological studyPatients receive high-dose oral vorinostat once daily on days 1-3 and leucovorin calcium and fluorouracil as in arm I. Courses repeat every 2 weeks in the absence of disease progression or 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 histologically or cytologically confirmed colorectal adenocarcinoma that is metastatic and which has failed standard treatment or for which no standard treatment is available
- Patients should have fluoropyrimidine-refractory disease; radiographic evidence of progression within 4 weeks from the last dose of a fluoropyrimidine-based regimen (at least 6 weeks of fluoropyrimidine-based treatment)
- Patients should have received and progressed on (or proved to be intolerant to) oxaliplatin and irinotecan; progression within 6 months from oxaliplatin-based therapy or irinotecan-based therapy is acceptable for eligibility
- Patients with KRAS wild-type or unknown KRAS status tumors should have progressed on or within 6 months from last cetuximab or panitumumab-based therapy; no prior cetuximab therapy is required for KRAS mutant tumors
- ECOG performance status =< 2
Key exclusion criteria (12 listed)
- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from significant adverse events due to agents administered more than 3 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other agents used in study
- Greater than Grade 2 neuropathy as defined by CTCAE version 3.0
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 |
|---|---|---|
| fluorouracilAlso: 5-fluorouracil, 5-Fluracil, 5-FU, AdrucilGiven IV | Drug | Arm I, Arm II |
| leucovorin calciumAlso: calcium folinate, CF, CFR, citrovorum factorGiven IV | Drug | Arm I, Arm II |
| vorinostatAlso: L-001079038, SAHA, suberoylanilide hydroxamic acid, ZolinzaGiven orally | Drug | Arm I, Arm II |
| pharmacological studyAlso: pharmacological studiesCorrelative study | Other | Arm I, Arm II |
Primary outcome
Disease Control Rate (Stable Disease or Objective Response)
Time frame: At 2 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
6 secondary outcomes
Median Progression-free Survival
Time frame: Every 8 weeks, up to 100 weeks.
Response Rate
Time frame: Every 8 weeks; up to 100 weeks.
Toxicity
Time frame: Daily
Overall Survival
Time frame: Every 12 weeks
Vorinostat Pharmacokinetics
Time frame: day 2 (cycle 1)
Fluorouracil Steady-state Pharmacokinetics
Time frame: Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Wen Wee MA, MD principal investigator
Roswell Park Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing fluorouracil, leucovorin calcium and vorinostat in people with Adenocarcinoma of the Colon and Adenocarcinoma of the Rectum, run by Roswell Park Cancer Institute 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 12 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 23 Jun 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Disease Control Rate (Stable Disease or Objective Response) (time frame: At 2 months). 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 23 Jun 2014.