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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-00083 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CDR0000439445 | |||
| I 55305 | Other Identifier | Roswell Park Cancer Institute | |
| 6789 | Other Identifier | CTEP |
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This phase I trial is studying the side effects and best dose of suberoylanilide hydroxamic acid when given together with fluorouracil, leucovorin, and oxaliplatin in treating patients with progressive metastatic or unresectable colorectal cancer or solid tumor. Drugs used in chemotherapy, such as suberoylanilide hydroxamic acid, fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Suberoylanilide hydroxamic acid may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of suberoylanilide hydroxamic acid when administered with fluorouracil, leucovorin calcium, and oxaliplatin in patients with progressive metastatic or unresectable colorectal cancer or other solid tumors.
SECONDARY OBJECTIVES:
I. Determine the toxicity of this regimen in these patients. II. Determine the pharmacokinetics of oxaliplatin, fluorouracil, and suberoylanilide hydroxamic acid in these patients.
OUTLINE: This is a dose-escalation study of suberoylanilide hydroxamic acid (SAHA).
Patients receive oral SAHA once or twice daily on days 1-3. Patients also receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 4 followed by fluorouracil IV over 46 hours on days 4-5. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA 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. A total of 10 patients are treated at the MTD.
After completion of study treatment, patients are followed for 4 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (vorinostat, mFOLFOX) | Experimental | Patients receive oral SAHA once or twice daily on days 1-3. Patients also receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 4 followed by fluorouracil IV over 46 hours on days 4-5. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA 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. A total of 10 patients are treated at the MTD. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| oxaliplatin | Drug | Given IV |
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|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose of vorinostat | Graded according to the NCI CTCAE. | 2 weeks |
| Grade 3, 4, or 5 adverse events graded using the NCI CTCAE version 4.0 | Up to 30 days after completion of study treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Response, evaluated using the new international criteria proposed by the RECIST committee | To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by repeat assessments that should be performed 4 weeks or more after the criteria for response are first met. | Up to 4 weeks after completion of study treatment |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marwan Fakih | Roswell Park Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Roswell Park Cancer Institute | Buffalo | New York | 14263 | United States |
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| leucovorin calcium | Drug | Given IV |
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| vorinostat | Drug | Given orally |
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| fluorouracil | Drug | Given IV |
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| Gene expression studies for evidence of up-regulation or down-regulation, obtained from microarray testing and changes in expression patterns of TS |
Carried out with real time quantitative RT-PCR assays. |
| Up to 4 weeks after completion of study treatment |
| Pharmacokinetic analysis for vorinostat and 5-FU | Days 1 and 15 |
| DPD activity | Tabulated by dose level. | Up to 8 days after the first dose of vorinostat (course 1) |
| ID | Term |
|---|---|
| D003110 | Colonic Neoplasms |
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| D000077150 | Oxaliplatin |
| D002955 | Leucovorin |
| D000077337 | Vorinostat |
| D005472 | Fluorouracil |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D000813 | Anilides |
| D000577 | Amides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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