Suberoylanilide Hydroxamic Acid, Fluorouracil, Leucovorin, and Oxaliplatin in Treating Patients With Progressive Metastatic or Unresectable Colorectal Cancer or Other Solid Tumors

NCT00138177 | Completed Phase 1

• 4 other identifiers: NCI-2009-00083CDR0000439445I 553056789
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (4)

• Response, evaluated using the new international criteria proposed by the RECIST committee

  Up to 4 weeks after completion of study treatment

• Gene expression studies for evidence of up-regulation or down-regulation, obtained from microarray testing and changes in expression patterns of TS

  Up to 4 weeks after completion of study treatment

• Pharmacokinetic analysis for vorinostat and 5-FU

  Days 1 and 15

• DPD activity

  Up to 8 days after the first dose of vorinostat (course 1)

Study Arms (1)

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.

Drug: oxaliplatin; Drug: leucovorin calcium; Drug: vorinostat; Drug: fluorouracil

Interventions

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP

Treatment (vorinostat, mFOLFOX)

leucovorin calcium DRUG

Given IV

Also known as: CF, CFR, LV

Treatment (vorinostat, mFOLFOX)

vorinostat DRUG

Given orally

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Treatment (vorinostat, mFOLFOX)

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Treatment (vorinostat, mFOLFOX)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed colorectal cancer
• Metastatic or unresectable disease OR diagnosis of solid tumor
• No known brain metastases
• ECOG 0-1 OR Karnofsky 70-100%
• Life expectancy \> 12 weeks
• Absolute neutrophil count ≥ 1,500/mm\^3
• WBC ≥ 3,000/mm\^3
• Platelet count ≥ 100,000/mm\^3
• Bilirubin normal
• AST and ALT ≤ 3 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Oxaliplatin; Leucovorin; Vorinostat; Fluorouracil

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Marwan Fakih

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2005
• First Posted: August 30, 2005
• Study Start: July 1, 2005
• Primary Completion: August 1, 2011
• Last Updated: September 30, 2013

Record last verified: 2013-09

Locations

US (1)