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Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00331955

Vorinostat and Doxorubicin in Treating Patients With Metastatic or Locally Advanced Solid Tumors

A Phase 1 study testing doxorubicin hydrochloride, vorinostat and pharmacological study in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial is studying the side effects and best dose of vorinostat when given together with doxorubicin in treating patients with metastatic or locally advanced solid tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
doxorubicin hydrochloride, vorinostat and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
Mar 2006to Jun 2012
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Histologically or cytologically confirmed solid tumor malignancies for which no curative therapy exists
  • Measurable or evaluable disease with tumor that is accessible to biopsy as determined by CT scan or ultrasound
  • Skin, lymph nodes, or chest wall lesions are allowed provided measurements are confirmed by 2 independent health care professionals
  • No uncontrolled CNS metastases
  • Patients with stable CNS metastases (either surgically resected, treated with gamma knife, or stable for 3 months after whole-brain radiotherapy and documented by MRI within the past 4 weeks) are eligible
  • Willing to undergo pre- and post-vorinostat tumor biopsies
Show all 34Show fewer
  • Life expectancy ≥ 3 months
  • ECOG performance status 0-2
  • WBC > 3,000/mm^3
  • Absolute neutrophil count > 1,500/mm^3
  • Hemoglobin > 9.0 g/dL
  • Platelet count > 100,000/mm^3 (transfusion independent)
  • Creatinine ≤ 2.0 mg/mL
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 1.5 times ULN
  • LVEF > 50%
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • Negative pregnancy test
  • Not pregnant or nursing
  • No significant active infection (e.g., pneumonia, cellulitis, or wound abscess)
  • No history of cardiac failure
  • No history of long QT syndrome (QTc > 470 msec)
  • No history of ventricular tachycardia or fibrillation
  • No history of seizures
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat or other agents used in the study
  • More than 3 weeks since prior chemotherapy or radiotherapy (2 weeks for weekly regimens)
  • More than 2 weeks since prior valproic acid or any other histone deacetylase inhibitors
  • No prior anthracycline exposure
  • No other concurrent chemotherapy
  • No concurrent hormonal therapy except for maintenance therapy with luteinizing-hormone releasing-hormone agonists
  • No concurrent antiarrhythmics
  • No concurrent steroids to control brain metastasis
  • No concurrent colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) during the first course of study treatment
  • No other concurrent investigational agents for primary disease

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: Phase I Trial of Vorinostat (NSC-701852, Suberoylanilide Hydroxamic Acid) and Doxorubicin (NSC-123127, Adriamycin)

This phase I trial is studying the side effects and best dose of vorinostat when given together with doxorubicin in treating patients with metastatic or locally 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 doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may help doxorubicin work better by making tumor cells more sensitive to the drug.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the safety and tolerability of vorinostat (SAHA) and doxorubicin hydrochloride in patients with metastatic or locally advanced solid tumors.

II. Determine the maximum tolerated dose of vorinostat when administered with doxorubicin hydrochloride in patients treated with this regimen.

SECONDARY OBJECTIVES:

  1. Determine the response rate (complete response [CR] and partial response [PR]) and clinical benefits rate (CR, PR, and stable disease > 12 weeks) in patients treated with this regimen.

II. Determine the pharmacokinetics and pharmacodynamics of vorinostat and doxorubicin hydrochloride and their interaction.

III. Determine the effects of vorinostat on histone acetylation in peripheral blood mononuclear cells and tumors.

IV. Determine the effects of vorinostat on DNA damage induced by doxorubicin hydrochloride as a function of topoisomerase II expression.

  1. Determine the effects of vorinostat on genes and proteins crucial for the maintenance of chromatin structure.

OUTLINE: This is a non-randomized, open-label, dose-escalation study of vorinostat.

Patients receive oral vorinostat twice daily for 5 doses on days 1-3, 8-10, and 15-17 and doxorubicin hydrochloride IV on days 3, 10, and 17. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 6 courses of treatment may continue to receive vorinostat alone in the absence of disease progression.

Cohorts of 3-6 patients receive escalating doses of vorinostat 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. Up to15 patients are treated at the MTD. Mandatory biopsies are required in these patients. Patients undergo blood collection and tumor biopsies periodically during the study for pharmacologic, pharmacokinetic, pharmacodynamic, and biomarker correlative studies.

After completion of study treatment, patients are followed for at least 30 days.

PROJECTED ACCRUAL: A total of 40 patients will be accrued to this study.

Being tested
doxorubicin hydrochloride, vorinostat, pharmacological study, laboratory biomarker analysis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

  • vorinostatDrug

    Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

    Given orally

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00331955
Study groupRoleWhat they receive
Treatment (vorinostat, doxorubicin hydrochloride)ExperimentalPatients receive oral vorinostat twice daily for 5 doses on days 1-3, 8-10, and 15-17 and doxorubicin hydrochloride IV on days 3, 10, and 17. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 6 courses of treatment may continue to receive vorinostat alone in the absence of disease progression.
Receives: Drug: doxorubicin hydrochloride; Drug: vorinostat; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability as assessed by NCI CTCAE v3.0

    Measured: Up to 30 days after completion of treatment

  2. Maximum tolerated dose (MTD) of vorinostat as assessed by NCI CTCAE v3.0

    Measured: 28 days

Secondary outcomes (4)

  1. Effects of vorinostat on histone acetylation

    Measured: At baseline and at day 3 prior

  2. Correlation of dose and response with biological markers for histone acetylation, Topo II expression, assays for comet moments and expression patterns of chromatin structural proteins dose

    Our initial analysis of efficacy will be descriptive and exploratory with the goal of discerning trends in various response endpoints and correlation with biological markers.

    Measured: Up to 30 days after completion of study treatment

  3. Response rate (CR and PR) and clinical benefits rate (CR, PR, and stable disease) according to RECIST

    Our initial analysis of efficacy will be descriptive and exploratory with the goal of discerning trends in various response endpoints and correlation with biological markers.

    Measured: Up to 30 days after completion of study treatment

  4. Duration of response (overall response, complete response, and stable disease)

    Using Cox regression with dose as an independent variable.

    Measured: Up to 30 days after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2006 (estimated)
  2. Study startMar 2006
  3. Primary completionJun 2012

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00331955
Sponsor's protocol ID
NCI-2012-02695
Other IDs
MCC 14193, CDR0000471997, NCI-6970, MCC-IRB-103476, R21CA112913
Status last verified
Jul 2013
First submitted
30 May 2006
Last updated
2 Jul 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing doxorubicin hydrochloride, vorinostat and pharmacological study in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) 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 34 inclusion and 0 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 2 Jul 2013. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety and tolerability as assessed by NCI CTCAE v3.0 (time frame: Up to 30 days after completion of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00331955.

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 2 Jul 2013.

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