RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy consisting of paclitaxel plus carboplatin given with amifostine and filgrastim in treating patients with recurrent or metastatic cancer.

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma	Drug: amifostine  Drug: carboplatin  Drug: filgrastim  Drug: paclitaxel	Phase I

Further Study Details: 

OBJECTIVES: I. Establish the maximum tolerated dose of a paclitaxel and carboplatin combination modulated by amifostine and filgrastim (G-CSF) in patients with recurrent or metastatic cancer.

II. Define the dose limiting toxicity of this combination in these patients.

III. Observe any antitumor responses in patients treated with this combination.

PROTOCOL OUTLINE: This is a dose escalation study of paclitaxel.

Patients receive a 10 minute infusion of amifostine followed by paclitaxel given intravenously over 3 hours followed by carboplatin given over 30 minutes. Filgrastim (G-CSF) is given subcutaneously daily for up to 10 days by self administration starting the following day. Treatment repeats every 28 days for at least 3 courses unless disease progression or unacceptable toxicity occurs. Patients who develop dose-limiting toxicity (DLT) on a given course receive one dose level lower on the next and subsequent courses. Patients with stable disease may continue treatment for as long as benefit is shown.

In the absence of DLT in the first 3 patients treated, subsequent cohorts of 3 patients each receive escalating doses of paclitaxel on the same schedule. If DLT occurs in 1 of 3 patients at a given dose level, then 3 additional patients are added at that dose. If DLT occurs in 1 additional patient, this dose is the maximum tolerated dose (MTD); if DLT occurs in more than 2 patients, then 3 additional patients are added at the previous dose. If DLT occurs in no more than 2 of 6 patients, this dose is considered the MTD. At any dose, 3 cases of DLT leads to discontinuation of recruitment at that dose.

PROJECTED ACCRUAL: Approximately 24 patients will be accrued for this study within 18 months.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven recurrent or metastatic malignant disease not amenable to curative surgery, radiotherapy, conventional chemotherapy, or investigational therapy of higher priority; Priority given to patients with lung cancer or cancers with tumors easily available for biopsy
• No CNS disease unless stable post radiation

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent immune stimulating agents
• Chemotherapy: At least 3 weeks since chemotherapy (6 weeks since nitrosourea or mitomycin) and recovered; No prior paclitaxel or carboplatin; No concurrent chemotherapy
• Endocrine therapy: No concurrent hormone therapy
• Radiotherapy: At least 3 weeks since radiotherapy to major bone marrow bearing areas and recovered; Concurrent radiotherapy allowed for vital indications or pain relief
• Surgery: At least 3 weeks since surgery

--Patient Characteristics--

• Age: Not specified
• Performance status: ECOG 0-2
• Life expectancy: At least 3 months
• Hematopoietic: WBC at least 4,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 mg/dL
• Renal: Creatinine no greater than 1.5 mg/dL; Creatinine clearance at least 50 mL/min
• Cardiovascular: Systolic blood pressure at least 90 mm Hg; No severe heart decompensation; No clinically significant cardiac arrhythmia on EKG; No inability to tolerate bradycardia
• Other: No active, uncontrolled infection; No nonmalignant systemic disease; Not pregnant or nursing; Effective contraception required of fertile patients

New York
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States

Study chairs or principal investigators

Gary N. Schwartz,  Study Chair,  Roswell Park Cancer Institute   

Study ID Numbers:  CDR0000066227; RPCI-DS-97-14; NCI-G98-1410
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003294
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08