Treating Patients With Advanced Solid Tumors, Breast Cancer or Recurrent Ovarian Cancer (BMS-247550)

• ClinicalTrials.gov Identifier: NCT00005807
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: October 9, 2018
• Sponsor: Albert Einstein College of Medicine
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Albert Einstein College of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Ovarian Cancer; Unspecified Adult Solid Tumor, Protocol Specific	Drug: BMS-247550	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Scientific Exploratory Study of Epothilone B Analog in Patients With Solid Tumors and Gynecological Malignancies
• Actual Study Start Date: July 2000
• Actual Primary Completion Date: August 2004
• Actual Study Completion Date: August 2004

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treated Participants; dose escalation treatment	Drug: BMS-247550; anticancer agent for the treatment of patients with malignant tumors.; Other Name: epothilone derivative

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New York

Albert Einstein Clinical Cancer Center

Bronx, New York, United States, 10461

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States, 10016

Sponsors and Collaborators

Albert Einstein College of Medicine

National Cancer Institute (NCI)

Investigators

• Study Chair: Franco M. Muggia, MD; NYU Langone Health
• Principal Investigator: Sridhar Mani, MD; Albert Einstein College of Medicine

More Information

Publications of Results:

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.

• Responsible Party: Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT00005807
• Other Study ID Numbers: CDR0000067800; AECM-9911378; NCI-98; NYU-0006
• First Posted: January 27, 2003
• Last Update Posted: October 9, 2018
• Last Verified: October 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Albert Einstein College of Medicine:

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

Additional relevant MeSH terms:

Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Epothilones; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents