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

PURPOSE: Phase II trial to study the effectiveness of alanosine in treating patients who have soft tissue sarcoma, sarcoma of the bone, mesothelioma, non-small cell lung cancer, or pancreatic cancer.

Condition	Treatment or Intervention	Phase
Gastrointestinal Cancer musculoskeletal cancer Osteosarcoma thorax and respiratory cancer	Drug: alanosine  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the response rates in patients with methylthioadenosine phosphorylase (MTAP)-deficient cancer when treated with alanosine.
• Determine the time to response and duration of response in patients treated with this drug.
• Determine the progression-free survival of patients treated with this drug.
• Determine the pharmacodynamic activity of this drug in these patients, based on special imaging to measure tumor adenosine triphosphate depletion.
• Determine the pharmacokinetic activity of this drug in these patients.
• Determine the safety and tolerability of this drug in these patients.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

Patients receive alanosine IV continuously on days 1-5. Treatment repeats every 21 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 28 days.

PROJECTED ACCRUAL: A total of 50-145 patients (10-29 per tumor type) will be accrued for this study.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignancy of any of the following types:
• Soft-tissue sarcoma
• High grade
• Chemotherapy naïve or progressive or metastatic after no more than 2 prior cytotoxic treatment regimens (not including adjuvant therapy)
• Sarcoma of the bone (including osteosarcoma* and chondrosarcoma)
• High grade
• Progressive or recurrent after no more than 2 prior cytotoxic treatment regimens
• No newly diagnosed or chemotherapy naïve disease NOTE: *Prior treatment with cisplatin and doxorubicin required
• Mesothelioma
• Unresectable
• Chemotherapy naïve or progressive after no more than 1 prior cytotoxic chemotherapy regimen
• Not amenable to curative treatment with surgery
• Evidence of gross unresectability includes, but is not limited to, direct extension into the chest wall, mediastinal or hilar lymphadenopathy, pulmonary or cardiac function that is inadequate to tolerate resection, and sarcomatoid or mixed histology
• Non-small cell lung cancer
• Stage III with malignant pleural or pericardial effusion, stage IV, or progressive after no more than 2 prior cytotoxic chemotherapy regimens
• No newly diagnosed or chemotherapy naïve disease
• Pancreatic cancer
• Stage IV adenocarcinoma after no more than 1 prior cytotoxic treatment regimen
• No newly diagnosed or chemotherapy naïve disease
• No Ewing's sarcoma of the soft tissue or bone
• Documented absence of methylthioadenosine phosphorylase on fixed tumor specimens
• Measurable disease
• For all tumor types, at least 1 lesion measurable by MRI or CT scan
• Chest x-ray allowed only for clearly defined lesions surrounded by aerated lung
• Soft tissue component of bone disease considered measurable provided it can be measured by MRI or CT scan
• Must be outside of a previously irradiated area
• No uncontrolled CNS metastases of primary tumor under study
• Patients with brain metastases are eligible only if the brain metastases have been treated with prior radiotherapy and/or surgery, are neurologically stable with no progressing symptoms, and are off steroids and anticonvulsants

PATIENT CHARACTERISTICS: Age

• 18 and over (13 and over for osteosarcoma only)

Performance status

• WHO 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN
• AST and ALT no greater than 2.5 times ULN (5 times ULN if liver metastases are present)

Renal

• Creatinine no greater than 1.5 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 4 weeks after study treatment
• No premalignant bony lesions (e.g., Paget's disease)
• No other concurrent active malignancy except completely excised nonmelanoma skin cancer or carcinoma in situ of the cervix or bladder
• No serious infection
• No medical or psychiatric condition that would preclude the achievement of the study objectives

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• More than 42 days since prior nitrosoureas or mitomycin

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• At least 28 days since prior brain radiotherapy
• More than 28 days since prior radiotherapy to more than 50% of the bone marrow

Surgery

• See Disease Characteristics
• At least 28 days since prior thoracic or other major surgery

Other

• Recovered from prior therapy
• More than 28 days since prior cytotoxic agents
• More than 28 days since prior anticancer investigational agents
• No other concurrent anti-tumor treatment

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States
California
      Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States
      Wilshire Oncology Medical Group, Incorporated - La Verne, La Verne,  California,  91750,  United States
Florida
      Lynn Regional Cancer Center West, Boca Raton,  Florida,  33428,  United States
Illinois
      Midwest Cancer Research Group, Incorporated, Skokie,  Illinois,  60077,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      St. Vincent's Comprehensive Cancer Center - Manhattan, New York,  New York,  10011,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6838,  United States
Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030,  United States
      U.S. Oncology, Incorporated, Houston,  Texas,  77060,  United States

Study chairs or principal investigators

Paul A. Meyers, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000304677; MSKCC-03029; SALMEDIX-SDX-102-01; NCT00062283
Record last reviewed:  March 2005
Last Updated:  March 10, 2005
Record first received:  June 5, 2003
ClinicalTrials.gov Identifier:  NCT00062283
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08