Clinical trial NCT00005807: Treating Patients With Advanced Solid Tumors, Breast Cancer or Recurrent Ovarian Cancer
Official title: A Phase I Scientific Exploratory Study of Epothilone B Analog in Patients With Solid Tumors and Gynecological Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Ovarian Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: stage IV breast cancer
stage IIIA breast cancer
recurrent breast cancer
stage IIIB breast cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
unspecified adult solid tumor, protocol specific
ovarian stromal cancer
stage III ovarian germ cell tumor
stage IV ovarian germ cell tumor
recurrent ovarian germ cell tumor
borderline ovarian surface epithelial-stromal tumor
ovarian sarcoma
male breast cancer
Lead sponsor: Albert Einstein College of Medicine
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of BMS-247550 in treating patients who have metastatic, recurrent, or locally advanced, ovarian cancer, breast cancer, or metastatic or unresectable solid tumors.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose, recommended phase II dose, and associated toxic effects of BMS-247550 in patients with advanced solid tumors.
* Determine the pharmacokinetic and pharmacodynamic relationship of this treatment regimen in these patients.
* Assess the extent of microtubule bundle and mitotic aster formation and cell cycle kinetics in peripheral blood mononuclear cells in these patients treated with this regimen.
* Determine any evidence of antitumor activity of this treatment regimen in these patients.
* Evaluate the relationship between tumor response and the occurrence of mutation in the class 1 isotype of B-tubulin and B-tubulin isotype distribution in patients with advanced or recurrent solid tumors, ovarian cancer, or breast cancer treated with this regimen.
* Investigate Multi-Drug Resistance Gene (MDR1), Multidrug Resistance-associated Protein (MRP) Gene, and canalicular multispecific organic anion transporter 1(cMOAT) messenger ribonucleic acid (mRNA) and protein expression as prognosticators of tumor response in these patients treated with this regimen.
* Determine the relationship between stathmin expression and phosphorylation status as a function of response in these patients treated with this regimen.
* Correlate the expression of proapoptotic (p53, bax, bad, and bid) and antiapoptotic (survivin, inhibitors of apoptotic proteins, bcl-2, and bcl-x) proteins in tumor samples and/or ascites with response and clinical outcome in these patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study.

* Part I: Patients with advanced solid tumors receive BMS-247550 IV over 1 hour every 3 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of BMS-247550 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 toxicity.

* Part II: Patients with ovarian, breast, or other cancer receive BMS-247550 as in the part I portion of the study at the MTD. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed at 2 months.

PROJECTED ACCRUAL: Approximately 42-66 patients will be accrued for this study within 12-16 months.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed metastatic or unresectable solid malignancy for which no standard or curative therapies exist or are no longer effective
* Metastatic, recurrent, or locally advanced breast, ovarian, or other cancer
* Hemoglobin at least 9.0 g/dL
* WBC at least 3,000/mm3
* Absolute neutrophil count at least 1,500/mm3
* Platelet count at least 100,000/mm3
* Bilirubin normal
* AST/ALT no greater than 3 times upper limit of normal
* Gilbert's syndrome allowed
* Creatinine no greater than 2 mg/dL

Exclusion Criteria:

* symptomatic congestive heart failure
* unstable angina pectoris
* cardiac arrhythmia
* grade 2 or greater clinical neuropathy
* prior allergy or hypersensitivity reaction (grade 2 or greater) to prior paclitaxel or other therapy containing Cremophor EL
* allergy or intolerance to steroids, diphenhydramine, cimetidine, or ranitidine
* uncontrolled concurrent illness
* active infection
* pregnant or nursing
* other concurrent anticancer therapies or commercial agents
* other concurrent investigational agents
* other concurrent highly active antiretroviral therapy for HIV-positive patients

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Albert Einstein Clinical Cancer Center
state: New York
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
Study officials:
affiliation: NYU Langone Health
name: Franco M. Muggia, MD
role: STUDY_CHAIR
affiliation: Albert Einstein College of Medicine
name: Sridhar Mani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McDaid HM, Mani S, Shen HJ, Muggia F, Sonnichsen D, Horwitz SB. Validation of the pharmacodynamics of BMS-247550, an analogue of epothilone B, during a phase I clinical study. Clin Cancer Res. 2002 Jul;8(7):2035-43.