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Recurrent Non-small Cell Lung CancerPhase 1NCT00084981

Decitabine and Valproic Acid in Treating Patients With Non-Small Cell Lung Cancer

A Phase 1 study testing decitabine, valproic acid and pharmacological study in people with Recurrent Non-small Cell Lung Cancer and Stage IV Non-small Cell Lung Cancer, 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 decitabine and valproic acid in treating patients with non-small cell lung cancer. Drugs used in chemotherapy, such as decitabine and valproic acid, work in different ways to stop tumor cells from dividing so they stop growing or die. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
decitabine, valproic acid and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
Apr 2004to Feb 2013
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 non-small cell lung cancer
  • Tumor accessible to biopsy by bronchoscopy, through surface biopsy (e.g., skin punch biopsy for skin/subcutaneous metastasis) or through CT scan guidance
  • Not eligible for curative surgery, chemotherapy, radiotherapy, or multimodality treatment options
  • No uncontrolled brain metastases
  • Controlled brain metastases allowed provided patient has no neurologic deterioration when off steroids; has completed prior radiotherapy or other treatments; has fully recovered from prior treatment; and does not require anticonvulsants
  • Performance status - ECOG 0-2
Show all 60Show fewer
  • Performance status - Karnofsky 60-100%
  • More than 12 weeks
  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • WBC > 3,000/mm^3
  • AST and ALT =< 2.5 times upper limit of normal (ULN)
  • Bilirubin =< 1.5 times ULN
  • Creatinine =< 1.5 times ULN
  • Creatinine clearance >= 60 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior allergic reaction to compounds of similar chemical or biological composition to decitabine, valproic acid, or other study agents
  • No other concurrent uncontrolled illness
  • No ongoing or active infection requiring antibiotics
  • No history of seizures requiring anticonvulsants
  • No medical problem that would preclude study participation
  • No psychiatric illness or social situation that would preclude study compliance
  • No other active malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix
  • No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or epoetin alfa)
  • No more than 3 prior chemotherapy regimens
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • Prior definitive radiotherapy to the chest allowed
  • Clinical (radiographic or other) evidence of tumor progression for previously irradiated indicator lesion in the chest
  • More than 2 weeks since prior radiotherapy and recovered
  • No concurrent palliative radiotherapy
  • Prior curative or palliative intent surgery allowed
  • At least 2 weeks since prior surgery and recovered
  • At least 4 weeks since prior photodynamic therapy
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer agents or therapies
  • No other concurrent investigational agents
  • No concurrent administration of any of the following medications:
  • Aspirin
  • Chronic low-dose (=< 81 mg/day) aspirin allowed
  • Felbamate
  • Rifampin
  • Amitriptyline
  • Nortriptyline
  • Carbamazepine
  • Clonazepam
  • Diazepam
  • Ethosuximide
  • Lamotrigine
  • Phenobarbital
  • Barbiturates
  • Primidone
  • Phenytoin
  • Zidovudine
  • No concurrent divalproex sodium
  • Concurrent gabapentin for neuropathic pain allowed

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Non-Small Cell Lung Cancer

This phase I trial is studying the side effects and best dose of decitabine and valproic acid in treating patients with non-small cell lung cancer. Drugs used in chemotherapy, such as decitabine and valproic acid, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the safety and tolerability of decitabine and valproic acid in patients with non-small cell lung cancer.

II. Determine the recommended phase II dose of this regimen in these patients.

SECONDARY OBJECTIVES:

  1. Determine the ability of this regimen to lead to biological changes in tumor and surrogate tissues in these patients, including hypomethylation of target genes known to be methylated in NSCLC (CDKN2, APC, BMP3B, CDH1 and RASSF1A) in biopsy specimens and surrogate tissues (peripheral blood mononuclear cells [PBMC] and plasma/serum DNA); acetylation and methylation changes in histones from tumor and surrogate tissues (PBMC and oral epithelial cells); inhibition of histone deacetylase (HDAC) activity in peripheral blood; pharmacokinetic analysis of Decitabine and Valproic Acid; DNA methyltransferase 1 (DNMT1) protein loss in PBMC and buccal cells; response of hemoglobin F in patients with non-hematologic conditions to DNMT and HDAC inhibition; and preliminary evidence of antitumor activity in non-small cell lung cancer.

OUTLINE: This is a dose-escalation study.

Patients receive decitabine IV over 1 hour on days 1-10 and oral valproic acid three times daily on days 5-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of decitabine and valproic acid 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. After the MTD is determined, an additional 6 patients are treated at that dose.

Being tested
decitabine, valproic acid, pharmacological study, laboratory biomarker analysis
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • decitabineDrug

    Also called 5-aza-dCyd, 5AZA, DAC

    Given IV

  • valproic acidDrug

    Also called Alti-Valproic, Depakene, Novo-Valproic, VA

    Given PO

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00084981
Study groupRoleWhat they receive
Treatment (decitabine, valproic acid)ExperimentalPatients receive decitabine IV over 1 hour on days 1-10 and oral valproic acid three times daily on days 5-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of decitabine and valproic acid until the 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. After the MTD is determined, an additional 6 patients are treated at that dose.
Receives: Drug: decitabine; Drug: valproic acid; 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. MTD, defined as dose in which fewer than 1/3 or 2/6 patients experience DLT

    Measured: 28 days

Timeline

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

  1. First posted11 Jun 2004 (estimated)
  2. Study startApr 2004
  3. Primary completionFeb 2013

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
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00084981
Sponsor's protocol ID
NCI-2012-01451
Other IDs
NCI-2012-01451, NCI-6237, OSU-2003C0087, OSU-0346, CDR0000367115, OSU 0346, 6237, U01CA076576
Status last verified
Sep 2013
First submitted
10 Jun 2004
Last updated
30 Sep 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing decitabine, valproic acid and pharmacological study in people with Recurrent Non-small Cell Lung Cancer and Stage IV Non-small Cell Lung Cancer, 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 60 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 30 Sep 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?

MTD, defined as dose in which fewer than 1/3 or 2/6 patients experience DLT (time frame: 28 days). 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 NCT00084981.

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 30 Sep 2013.

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