High-Dose or Low-Dose Vorinostat in Combination With Carboplatin or Paclitaxel in Treating Patients With Advanced Solid Tumors

NCT01281176 | Active Not Recruiting Phase 1 DMC

• 7 other identifiers: NCI-2011-02575CDR0000693736UCCRC-10-652-B10-652-B8844P30CA014599U01CA069852
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized pilot clinical trial studies high-dose or low-dose vorinostat in combination with carboplatin or paclitaxel in treating patients with advanced solid tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving different doses of vorinostat together with carboplatin or paclitaxel may kill more tumor cells.

Conditions

Adult Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Peak concentrations (Cmax) of vorinostat at 400, 1200, and 1600 mg

  0 (pre-treatment), 60, 120, 180, 240, 360 and 480 minutes and 24 hours after vorinostat administration on days 3 and 10 of course 0 and on day 3 of course 1

Secondary Outcomes (2)

• Adverse events of two different escalated intermittent dosing schedules of vorinostat combined with carboplatin as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 4 weeks

• Pharmacodynamic markers of vorinostat activity, including AUC and changes in platelet counts

  0 (pre-treatment), 60, 120, 180, 240, 360 and 480 minutes and 24 hours after vorinostat administration on days 3 and 10 of course 0 and on day 3 of course 1

Study Arms (6)

Arm I (high- and low-dose vorinostat and carboplatin)

EXPERIMENTAL

Patients receive high-dose vorinostat PO QD on days 1-3 and low-dose vorinostat PO QD on days 8-10 (course 0). After 5 days, patients receive high-dose vorinostat PO QD on days 1-3 and carboplatin IV over 30 minutes on day 3 of all subsequent courses.

Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vorinostat

Arm II (high- and low-dose vorinostat and carboplatin)

EXPERIMENTAL

Patients receive high-dose vorinostat and low-dose vorinostat as in Arm I. After 5 days, patients receive lower-dose vorinostat PO QD on days 1-3 and carboplatin IV over 30 minutes on day 3.

Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vorinostat

Arm III (low- and high-dose vorinostat and carboplatin)

EXPERIMENTAL

Patients receive low-dose vorinostat PO QD on days 1-3 and high-dose vorinostat PO QD on days 8-10 (course 0). After 5 days, patients receive vorinostat and carboplatin as in Arm I.

Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vorinostat

Arm IV (low- and high-dose vorinostat and carboplatin)

EXPERIMENTAL

Patients receive low-dose vorinostat and high-dose vorinostat as in Arm III. After 5 days, patients receive vorinostat and carboplatin as in Arm II.

Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vorinostat

Arm V (low- and mid-dose vorinostat and paclitaxel)

EXPERIMENTAL

Patients receive low-dose vorinostat PO QD on days 1-3 and mid-dose vorinostat PO QD on days 8-10 (course 0). After 5 days, patients receive mid-dose vorinostat PO QD on days 1-3 and paclitaxel IV over 3 hours on day 3.

Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study; Drug: Vorinostat

Arm VI (mid- and low-dose vorinostat and paclitaxel)

EXPERIMENTAL

Patients receive mid-dose vorinostat PO QD on days 1-3 and low-dose vorinostat PO QD on days 8-10. After 5 days, patients receive vorinostat and paclitaxel as in Arm V.

Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study; Drug: Vorinostat

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm I (high- and low-dose vorinostat and carboplatin); Arm II (high- and low-dose vorinostat and carboplatin); Arm III (low- and high-dose vorinostat and carboplatin); Arm IV (low- and high-dose vorinostat and carboplatin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (high- and low-dose vorinostat and carboplatin); Arm II (high- and low-dose vorinostat and carboplatin); Arm III (low- and high-dose vorinostat and carboplatin); Arm IV (low- and high-dose vorinostat and carboplatin); Arm V (low- and mid-dose vorinostat and paclitaxel); Arm VI (mid- and low-dose vorinostat and paclitaxel)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm V (low- and mid-dose vorinostat and paclitaxel); Arm VI (mid- and low-dose vorinostat and paclitaxel)

Pharmacological Study OTHER

Correlative studies

Arm I (high- and low-dose vorinostat and carboplatin); Arm II (high- and low-dose vorinostat and carboplatin); Arm III (low- and high-dose vorinostat and carboplatin); Arm IV (low- and high-dose vorinostat and carboplatin); Arm V (low- and mid-dose vorinostat and paclitaxel); Arm VI (mid- and low-dose vorinostat and paclitaxel)

Vorinostat DRUG

Given PO

Also known as: L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Arm I (high- and low-dose vorinostat and carboplatin); Arm II (high- and low-dose vorinostat and carboplatin); Arm III (low- and high-dose vorinostat and carboplatin); Arm IV (low- and high-dose vorinostat and carboplatin); Arm V (low- and mid-dose vorinostat and paclitaxel); Arm VI (mid- and low-dose vorinostat and paclitaxel)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which no superior curative or palliative measures are known
• At least 4 weeks must have passed since prior chemotherapy or radiation therapy; 6 weeks if the last regimen included BCNU or mitomycin C
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy of greater than 3 months
• Leukocytes \> 3,000/mcL
• Absolute neutrophil count \> 1,500/mcL
• Platelets \> 100,000/mcL
• Total bilirubin \< institutional upper limits of normal
• Potassium \< institutional upper limits of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 X institutional upper limit of normal, or \< 5 x ULN if liver metastases are present
• Creatinine within normal institutional limits OR creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• 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 adverse events due to agents administered more than 4 weeks earlier (except alopecia, lymphopenia, hyperglycemia, hypoalbuminemia and elevated serum alkaline phosphatase); all other toxicities should have resolved to grade 1 or less prior to beginning treatment
• Patients may not be receiving any other investigational agents
• Patients with known brain metastases that are untreated or have progressed after definitive therapy should be excluded from this clinical trial; patients with treated brain metastases, who are no longer receiving steroids for at least 14 days, are not receiving enzyme-inducing anti-epileptic drugs, and have no unstable neurologic symptoms may be enrolled at the discretion and joint decision of the principal investigator and treating physician
• Prior or current use of valproic acid, a histone deacetylase (HDAC) inhibitor
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, vorinostat or carboplatin
• Inability to swallow oral medications
• 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
• Women that are pregnant or breastfeeding are excluded from this study; all women of child-bearing potential must have a negative pregnancy test before receiving vorinostat; women of child-bearing potential and men must agree to use adequate contraception for the duration of the study; breastfeeding should be discontinued if the mother is treated with vorinostat; these potential risks may also apply to other agents used in this study; subjects that become pregnant or think they may be pregnant while taking part in this study should notify their treating physician immediately
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Interventions

Carboplatin; Paclitaxel; Taxes; Vorinostat

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Michael L Maitland

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 20, 2011
• First Posted: January 21, 2011
• Study Start: February 9, 2011
• Primary Completion: April 30, 2014
• Study Completion (Estimated): April 17, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)