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

Brief Title

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

Official Title

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

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.

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 Phase

Phase 1

Study Type

Interventional

Condition

Esophageal Cancer

Intervention

decitabine

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Start Date

October 1999

Eligibility Criteria

        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

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

David S. Schrump, MD, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT00019825

Organization ID

CDR0000067228

Secondary IDs

NCI-99-C-0129

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

David S. Schrump, MD, Study Chair, NCI - Surgery Branch

Verification Date

July 2004