Carboxyamidotriazole and Paclitaxel in Treating Patients With Advanced Solid Tumors or Refractory Lymphomas

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of carboxyamidotriazole and paclitaxel in treating patients with advanced solid tumors or refractory lymphomas.

OBJECTIVES:

* Determine the maximum tolerated dose of paclitaxel when combined with carboxyamidotriazole in patients with advanced solid tumors or refractory lymphomas.
* Determine the pharmacokinetics and toxicities of this regimen in these patients.
* Identify diseases for which this combination appears active.

OUTLINE: This is a dose escalation study.

Patients receive oral carboxyamidotriazole (CAI) daily with paclitaxel IV over 3 hours on day 8 and every 3 weeks thereafter. Course 1 is 28 days and all other subsequent courses are 21 days. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response receive 2 additional courses of treatment.

Sequential dose escalation of CAI is followed by sequential dose escalation of paclitaxel. Dose escalation in cohorts of 3 to 6 patients each continues 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.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically diagnosed solid tumor (i.e., breast and ovarian epithelial carcinomas) or lymphoma

  * Slides reviewed at the NCI Laboratory of Pathology
* Failure on therapy of proven efficacy for the disease

  * Prior therapy not required for the following metastatic diseases:

    * Melanoma
    * Non-small cell lung cancer
    * Renal cell carcinoma
* No brain metastases

  * Primary brain tumors (such as glioblastoma multiforme) with stable neurologic deficits allowed
* Measurable or evaluable disease required

  * Demonstrated by physical exam or on radiograph within 2 weeks prior to initiation of treatment OR
  * Elevated PSA associated with prostate cancer

    * Other marker-only disease ineligible

PATIENT CHARACTERISTICS:

Age:

* Over 18

Performance status:

* ECOG 0-2

Life expectancy:

* At least 3 months

Hematopoietic:

* WBC at least 3,000/mm\^3
* Platelet count at least 100,000/mm\^3
* Hematocrit at least 27%

Hepatic:

* Liver function tests no greater than 2 times upper limit of normal
* Bilirubin normal
* PT or PTT no greater than 1.25 times upper limit of normal
* Clotting parameters normal
* No concurrent anticoagulants other than 1 mg of warfarin per day for prophylaxis

Renal:

* Creatinine no greater than 1.5 mg/dL OR
* Creatinine clearance at least 45 mL/min
* No kidney obstruction

Cardiovascular:

* No cardiac conduction defect requiring antiarrhythmics
* No evidence of myocardial infarction or other myocardial damage within past 6 months

Other:

* HIV negative
* No concurrent infection
* No guaiac-positive stool test
* No neuropathy greater than grade I (unless associated with fixed-deficit primary brain tumors)
* Not pregnant or nursing
* Fertile patients must use effective contraception during and for 2 months after study

PRIOR CONCURRENT THERAPY:

* Recovery from prior therapy required

Biologic therapy:

* At least 4 weeks since prior biologic therapy

Chemotherapy:

* At least 4 weeks since prior chemotherapy (6 weeks since mitomycin, nitrosoureas, or carboplatin)
* No progression on carboxyamidotriazole or paclitaxel
* At least 6 months between treatment and relapse

Endocrine therapy:

* At least 4 weeks since prior hormonal therapy
* No concurrent corticosteroids except as physiologic replacement

Radiotherapy:

* At least 4 weeks since prior radiotherapy

Surgery:

* Not specified

Other:

* At least 1 week since prior therapeutic antibiotics
* Concurrent prophylactic antibiotics allowed except imidazole antifungals (e.g., ketoconazole, fluconazole)
* No concurrent calcium channel blockers