RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining topotecan and paclitaxel in treating patients who have advanced non-small cell lung cancer or other advanced solid tumors.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific Quality of Life	Drug: paclitaxel  Drug: topotecan	Phase I Phase II

Further Study Details: 

OBJECTIVES: Phase I: I. Determine the maximum tolerated dose (MTD) of oral topotecan combined with a fixed dose of paclitaxel in patients with advanced non-small lung cancer (NSCLC) and other advanced solid tumors. II. Determine the response rate of NSCLC patients treated at the MTD of oral topotecan combined with intravenous paclitaxel. III. Determine the dose limiting toxicities of this drug combination in this patient population. Phase II: IV. Determine the toxicities of this regimen at its MTD in patients with NSCLC. V. Determine time to response, response duration, survival, time to progression, and rate of stable disease of patients with NSCLC treated with this regimen at the MTD. VI. Assess changes in well-being of patients with NSCLC treated with this regimen at the MTD.

PROTOCOL OUTLINE: This is a dose escalation study of topotecan. Patients receive oral topotecan on days 1-5 and paclitaxel IV over 3 hours on day 1. Treatment continues every 21 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities. Once the MTD is determined, additional patients with non-small cell lung cancer are accrued to receive treatment with topotecan and paclitaxel at the recommended phase II dose. Quality of life is assessed in the phase II portion of the study at baseline, before each treatment course, and at the end of the study. Patients are followed at 3 weeks.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for the phase I dose escalation portion of this study. A total of 14-40 additional non-small cell lung cancer patients will be accrued to the phase II portion of this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Phase I: Advanced solid tumors, including non-small cell lung cancer (NSCLC), that have failed conventional therapy or for which no standard effective therapy exists
• May have failed conventional chemotherapy for tumor type; Chemotherapy naive NSCLC allowed
• Measurable or evaluable disease
• Phase II: Stage IIIB or IV NSCLC not amenable to surgery or radiotherapy with curative intent
• No prior chemotherapy allowed
• At least 1 bidimensionally measurable non-CNS indicator lesion defined by diagnostic studies; Measurable disease on CT or MRI scan must have one diameter at least 1 cm and one diameter at least 2 cm; Measurable disease on chest x-ray must have both diameters at least 2 cm; Palpable tumor masses that cannot be evaluated radiologically must have two diameters at least 2 cm; Measurable skin lesion must have at least one diameter at least 1 cm and its presence must be evaluated by a photograph; At least 6 weeks since prior radiotherapy to measurable, progressive disease
• No brain and/or leptomeningeal metastases by CT or MRI brain scan unless asymptomatic on neurologic exam and not receiving corticosteroid therapy to control symptoms

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent immunotherapy
• Chemotherapy: See Disease Characteristics; No other concurrent chemotherapy
• Endocrine therapy: See Disease Characteristics
• Radiotherapy: See Disease Characteristics; At least 4 weeks since palliative radiotherapy and recovered; No prior radiotherapy to greater than 30% of bone marrow reserve; No concurrent radiotherapy
• Surgery: See Disease Characteristics; At least 4 weeks since prior surgery (lesser period acceptable if deemed in best interest of patient)
• Other: No concurrent metoclopramide or cisapride to maintain motility or gastric emptying; At least 30 days or 5 half-lives since other prior investigational drugs for treatment of cancer; No other concurrent investigational medication

--Patient Characteristics--

• Age: 18 and over
• Performance status: WHO 0-2
• Life expectancy: At least 12 weeks
• Hematopoietic: WBC at least 3,000/mm3; Neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin normal; SGOT/SGPT no greater than 1.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present); Alkaline phosphatase no greater than 1.5 times ULN (5 times ULN if liver metastases present)
• Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception for 3 months prior to and during study; Able to take oral medication; No active infection; No other prior or concurrent malignancies except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; No other severe medical problem unrelated to malignancy that would preclude study compliance or expose patient to extreme risk; No condition of the gastrointestinal (GI) tract or otherwise that would affect GI absorption and motility; No history of hypersensitivity reactions to paclitaxel or other drugs formulated in polyoxyethylated castor oil

Study chairs or principal investigators

Robert Alan Figlin,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067543; UCLA-9904034; NCI-G00-1676; SB-104864/250
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  March 7, 2000
ClinicalTrials.gov Identifier:  NCT00004979
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08