Clinical trial NCT00019019: Carboxyamidotriazole and Paclitaxel in Treating Patients With Advanced Solid Tumors or Refractory Lymphomas
Official title: A PHASE I STUDY OF THE COMBINATION OF CAI AND PACLITAXEL IN ADULT PATIENTS WITH REFRACTORY CANCERS OR LYMPHOMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Breast Cancer
Kidney Cancer
Lung Cancer
Lymphoma
Melanoma (Skin)
Ovarian Cancer
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
stage IV breast cancer
stage IIIA breast cancer
recurrent breast cancer
stage IIIB breast cancer
recurrent non-small cell lung cancer
recurrent adult Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
stage III renal cell cancer
stage IV renal cell cancer
recurrent renal cell cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
recurrent adult brain tumor
small intestine lymphoma
adult brain stem glioma
adult craniopharyngioma
adult medulloblastoma
adult meningioma
adult glioblastoma
stage III melanoma
stage IV melanoma
recurrent melanoma
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IIIC breast cancer
stage IV non-small cell lung cancer
unspecified adult solid tumor, protocol specific
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
adult anaplastic astrocytoma
adult myxopapillary ependymoma
adult anaplastic ependymoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult central nervous system germ cell tumor
primary central nervous system non-Hodgkin lymphoma
adult pilocytic astrocytoma
adult subependymoma
adult ependymoblastoma
adult pineocytoma
adult pineoblastoma
adult meningeal hemangiopericytoma
intraocular lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
adult choroid plexus tumor
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
adult grade III meningioma
adult oligodendroglioma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Bethesda
country: United States
facility: NCI - Medical Oncology Clinical Research Unit
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Virginia Kwitkowski, MS, RN, CS, CRNP
role: STUDY_CHAIR
References:
citation: Kohn EC, Reed E, Sarosy GA, Minasian L, Bauer KS, Bostick-Bruton F, Kulpa V, Fuse E, Tompkins A, Noone M, Goldspiel B, Pluda J, Figg WD, Liotta LA. A phase I trial of carboxyamido-triazole and paclitaxel for relapsed solid tumors: potential efficacy of the combination and demonstration of pharmacokinetic interaction. Clin Cancer Res. 2001 Jun;7(6):1600-9.