Decitabine in Treating Patients With Unresectable Lung or Esophageal Cancer or Malignant Mesothelioma of the Pleura

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00019825

Collaborator

(none)

Locations

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of decitabine in treating patients who have unresectable lung or esophageal cancer or malignant mesothelioma of the pleura.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer Lung Cancer Malignant Mesothelioma Metastatic Cancer	Drug: decitabine	Phase 1

Detailed Description

OBJECTIVES:

Determine the pharmacokinetics, toxicity, and maximum tolerated dose of decitabine in patients with unresectable primary small cell or non-small cell lung cancer, unresectable esophageal cancer, or malignant pleural mesothelioma.
Measure the expression of NY-ESO-1 in tissue samples of these patients before and after receiving this drug.
Assess the serologic response to NY-ESO-1 in these patients before and after receiving this drug.
Measure the expression of p16 tumor suppressor gene in these patients before and after receiving this drug.

OUTLINE: This is a dose-escalation study for each stratification group. Patients are stratified according to number of prior therapies (2 or fewer vs 3 or more).

Patients receive decitabine IV continuously on days 1-3. Treatment repeats every 5 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease after completion of the second course receive 2 additional courses.

Cohorts of 3-6 patients receive escalating doses of decitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined for a particular stratum, additional patients from that stratum are treated at the MTD.

Patients are followed for 1 month.

PROJECTED ACCRUAL: A maximum of 72 patients (36 per stratum) will be accrued for this study.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Phase I Study of Decitabine Mediated Induction of Tumor Antigen and Tumor Suppressor Gene Expression in Lung Cancer Patients

Study Start Date :

Oct 1, 1999

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed unresectable primary small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), unresectable esophageal cancer, malignant pleural mesothelioma, or pleural effusions secondary to extrathoracic malignancies
Disease must be readily accessible to biopsy by endoscopy or percutaneous fine-needle aspiration
Extrathoracic metastatic disease allowed if no evidence of active intracranial or leptomeningeal metastases
Patients treated with prior resection or radiotherapy for intracranial metastatic disease may be eligible provided there is no evidence of active disease on two MRIs (taken one month apart) and patients require no anticonvulsant medications or steroids to control residual symptoms
No limited stage SCLC or operable NSCLC

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

At least 6 months

Hematopoietic:

Platelet count greater than 100,000/mm^3
Hemoglobin greater than 10 g/dL
WBC greater than 3,500/mm^3

Hepatic:

PT normal
Bilirubin less than 1.5 times upper limit of normal

Renal:

Creatinine no greater than 1.6 mg/dL OR
Creatinine clearance greater than 60 mL/min

Cardiovascular:

Any of the following conditions require clearance by a cardiologist:
Prior coronary artery disease
Prior transmural myocardial infarction
Congestive heart failure
Fixed defects on thallium scan with ejection fraction greater than 40%
No unstable angina
No recent deep venous thrombosis requiring anticoagulation

Pulmonary:

FEV1 and DLCO greater than 30% of predicted
pCO_2 less than 50 mm Hg
pO_2 greater than 60 mm Hg on room air
No recent pulmonary embolism requiring anticoagulation

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No active infection
HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 30 days since prior biologic therapy for the malignant tumor

Chemotherapy:

No prior decitabine
At least 30 days since other prior chemotherapy for the malignant tumor

Endocrine therapy:

See Disease Characteristics

Radiotherapy:

See Disease Characteristics
At least 30 days since prior radiotherapy for the malignant tumor (14 days for localized radiotherapy to nontarget lesions) and recovered

Surgery:

See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
2	Center for Cancer Research	Bethesda	Maryland	United States	20892