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

NCT ID: NCT00019825

Last Updated: 2015-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-10-31

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.

Conditions

Esophageal Cancer; Lung Cancer; Malignant Mesothelioma; Metastatic Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

decitabine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

David S. Schrump, MD

Role: STUDY_CHAIR

NCI - Surgery Branch

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Center for Cancer Research

Bethesda, Maryland, United States

Countries

United States

References

Weiser TS, Guo ZS, Ohnmacht GA, Parkhurst ML, Tong-On P, Marincola FM, Fischette MR, Yu X, Chen GA, Hong JA, Stewart JH, Nguyen DM, Rosenberg SA, Schrump DS. Sequential 5-Aza-2 deoxycytidine-depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO-1. J Immunother. 2001 Mar-Apr;24(2):151-61. doi: 10.1097/00002371-200103000-00010.

Reference Type: BACKGROUND

PMID: 11265773 (View on PubMed)

Weiser TS, Ohnmacht GA, Guo ZS, Fischette MR, Chen GA, Hong JA, Nguyen DM, Schrump DS. Induction of MAGE-3 expression in lung and esophageal cancer cells. Ann Thorac Surg. 2001 Jan;71(1):295-301; discussion 301-2. doi: 10.1016/s0003-4975(00)02421-8.

Reference Type: BACKGROUND

PMID: 11216765 (View on PubMed)

Other Identifiers

NCI-99-C-0129

Identifier Type: -

Identifier Source: secondary_id

NCI-T99-0012

Identifier Type: -

Identifier Source: secondary_id

CDR0000067228

Identifier Type: -

Identifier Source: org_study_id

NCT00001824

Identifier Type: -

Identifier Source: nct_alias