RATIONALE: Drugs used in chemotherapy use different ways to stop tumors from dividing so they stop growing or die. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of amifostine plus combination chemotherapy in treating patients with advanced cancer.

Condition	Treatment or Intervention	Phase
Cancer	Drug: amifostine  Drug: carboplatin  Drug: cyclophosphamide  Drug: sargramostim	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the effects of priming on the granulocyte and thrombocyte nadirs produced by high dose cyclophosphamide and carboplatin in patients with advanced malignancies.

II. Determine the effects of amifostine on the granulocyte and thrombocyte nadirs produced by this same regimen when administered with sargramostim primed progenitor cells.

III. Determine the maximum tolerated dose of cyclophosphamide and carboplatin that can be administered with sargramostim primed progenitor cells.

PROTOCOL OUTLINE: This is a dose escalation study.

Patients receive intravenous amifostine over 10 minutes on day 0, followed by intravenous cyclophosphamide and carboplatin consecutively over 5-15 minutes. Sargramostim is administered subcutaneously on days -7 to -2 and again beginning on day 1 until absolute neutrophil count is appropriate. Course is repeated every 28 days until disease progression or unacceptable toxic effects are observed. Nonresponding patients discontinue treatment after 2 courses. Patients are treated for a maximum of 6 courses.

Groups of 3-6 patients receive escalating doses of cyclophosphamide and carboplatin until the maximum tolerated dose (MTD) is determined. If dose limiting toxicity (DLT) occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the next lower dose is declared the MTD.

PROJECTED ACCRUAL: Approximately 24-30 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven advanced malignancies that are sensitive to cyclophosphamide/carboplatin therapy OR refractory to standard therapy, including, but not limited to:

Ovarian epithelial cancer; Colorectal cancer; Breast cancer; Sarcoma; Non-small cell lung cancer; Malignant melanoma; Upper gastrointestinal cancers; Small cell lung cancer

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent immunotherapy
• Chemotherapy: At least 3 weeks since prior chemotherapy and recovered; No more than 1 prior chemotherapy regimen for advanced or recurrent malignancies (not including adjuvant chemotherapy); No prior nitrosoureas or intravenous mitomycin; No concurrent cytotoxic chemotherapy.
• Endocrine therapy: At least 1 week since prior hormone therapy and recovered; Concurrent corticosteroid therapy allowed.
• Radiotherapy: At least 3 weeks since prior radiotherapy and recovered; Radiotherapy allowed to no more than 1 site in the thoracic or lumbar spine or pelvis; Concurrent radiotherapy to a symptomatic lesion allowed after the first course of study treatment.
• Surgery: At least 3 weeks since prior surgery and recovered (excluding recent biopsy or placement of an intravenous access device.

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2; SWOG 0-2
• Life expectancy: At least 3 months
• Hematopoietic: WBC at least 3,500/mm3; Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 8.5 g/dL.
• Hepatic: Bilirubin no greater than 1.5 mg/dL
• Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min OR Iothalamate clearance at least 60 mL/min.
• Cardiovascular: No significant coronary artery disease (angina of New York Heart Association class 3 or greater).
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No psychosis.

Ohio
      Cleveland Clinic Cancer Center, Cleveland,  Ohio,  44195,  United States

Study chairs or principal investigators

G. Thomas Budd,  Study Chair,  Cleveland Clinic Foundation Hospital   

Study ID Numbers:  CDR0000066347; CCF-IRB-1907; NCI-V98-1424; IMMUNEX-001.G9701
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004036
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08