Vorinostat and Gemcitabine in Treating Patients With Metastatic or Unresectable Solid Tumors

NCT00243100 | Completed Phase 1

• 5 other identifiers: NCI-2009-00091CDR00004454012005-01406865U01CA062461
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of vorinostat and gemcitabine in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy, such as vorinostat and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• Maximally tolerated dose of a combination of SAHA and gemcitabine determined by dose-limiting toxicity as measured by NCI CTCAE v3.0 continuously

  21 days

• Pharmacokinetics of SAHA

  -0.5, 0.5, 1, 2, 2.5, 3, 4, 6 and 8 hours after day 1 dose; -0.5 hours day 2; and -0.5, 0.5, 1, 2, 2.5, 3, 4, 6 and 8 hours day 3

Secondary Outcomes (1)

• Best overall response (complete + partial response rate) as measured radiologically by RECIST

  Up to 6 years

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral vorinostat (SAHA) once daily on days 1-14 and gemcitabine IV over 1-2 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA and gemcitabine 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 minimum of 6 patients are treated at the MTD

Drug: vorinostat; Drug: gemcitabine hydrochloride

Interventions

vorinostat DRUG

Given orally

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

Arm I

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Arm I

Eligibility Criteria

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

You may qualify if:

• ECOG 0-2 OR Karnofsky 60-100%
• AST and ALT =\< 2.5 times ULN
• Bilirubin =\< 1.5 times upper limit of normal (ULN)
• Platelet count \>= 100,000/mm3
• Absolute neutrophil count \>= 1,500/mm3
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Any number and type of prior chemotherapies are allowed including prior use of gemcitabine chemotherapy. A washout phase of at least 2 weeks since use of prior chemotherapy or radiation therapy, 6 weeks if the last regimen included nitrosoureas or mitomycin C, is required.
• Patients must have histologically confirmed epithelial malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Ability to understand and the willingness to sign a written informed consent document.
• Patients must have at least one measurable lesion as per the RECIST Criteria that can be accurately measured in at least one dimension, with minimum lesion size equal to or more than twice the slice thickness of the imaging study used.

You may not qualify if:

• No symptomatic congestive heart failure
• No cardiac arrhythmia
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No history of allergy, significant side effects, or poor tolerance to gemcitabine
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to vorinostat (SAHA)
• At least 2 weeks since prior radiotherapy
• Recovered from prior therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other uncontrolled illness
• More than 2 weeks since prior valproic acid
• No other concurrent investigational drugs
• No other concurrent anticancer therapy
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

Vorinostat; Gemcitabine

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Gauri Varadhachary

  M.D. Anderson Cancer Center

  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: October 20, 2005
• First Posted: October 21, 2005
• Study Start: November 1, 2005
• Primary Completion: August 1, 2011
• Last Updated: December 16, 2013

Record last verified: 2013-12

Locations

US (1)