Ixabepilone in Treating Patients With Recurrent or Persistent Endometrial Cancer

A Phase II Evaluation of Ixabepilone (BMS-247550) [NCI-Supplied Agent, NSC #710428]) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well ixabepilone works in treating patients with recurrent or persistent endometrial cancer.

Study Overview

• Status: Completed
• Conditions: Recurrent Endometrial Carcinoma; Endometrial Adenocarcinoma; Stage IV Endometrial Carcinoma
• Intervention / Treatment: Drug: ixabepilone

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the response rate in patients with recurrent or persistent endometrial adenocarcinoma treated with ixabepilone.

II. Determine the nature and degree of toxicity of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 19-51 patients will be accrued for this study within 2.5 years.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Gynecologic Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed endometrial adenocarcinoma

  • Recurrent or persistent disease

    • Histologic confirmation of the original primary tumor is required

  • Not amenable to management with any of the following:

    • Surgery
    • Radiotherapy
    • Higher priority or standard chemotherapy

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., palpation, plain x-ray, CT scan, or MRI) OR ≥ 10 mm by spiral CT scan

• At least 1 target lesion

  • Tumors within a previously irradiated field are designated as non-target lesions
  • Disease in an irradiated field as the only site of measurable disease is acceptable as a target lesion only if there has been clear progression of the lesion at least 90 days after completion of radiotherapy
• Received 1, and only 1, prior chemotherapy regimen (e.g., high-dose therapy, consolidation, or extended therapy administered after surgery or non-surgical assessment) for management of endometrial adenocarcinoma
• Ineligible for a higher priority Gynecologic Oncology Group (GOG) protocol (e.g., any active GOG phase III study for the same patient population)
• Performance status - GOG 0-2
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST (aspartate aminotransferase) ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN
• Sensory or motor neuropathy ≤ grade 1
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection requiring antibiotics
• No other invasive malignancies within the past 5 years except non-melanoma skin cancer
• At least 3 weeks since prior biologic or immunologic agents directed at the malignant tumor
• One prior non-cytotoxic* (biologic or cytostatic) regimen for management of recurrent or persistent disease allowed
• See Disease Characteristics
• Prior paclitaxel or docetaxel allowed
• Recovered from prior chemotherapy
• No more than 1 prior cytotoxic chemotherapy regimen (either single or combination drug therapy)
• No prior ixabepilone

• At least 1 week since prior hormonal therapy directed at the malignant tumor

  • Continuation of hormone replacement therapy allowed
• See Disease Characteristics
• Recovered from prior radiotherapy
• Recovered from prior surgery
• At least 3 weeks since other prior therapy directed at the malignant tumor
• No prior cancer treatment that contraindicates study therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (ixabepilone); Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: ixabepilone; Given IV; Other Names: BMS-247550; epothilone B lactam; Ixempra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response	RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.	Every other cycle for first 6 months; then every six months thereafter until completion of study treatment; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease
Frequency and Severity of Observed Adverse Effects Associated With Protocol Therapy (CTCAE Version 3)		Every cycle until completion of study treatment up to 30 days after stopping study treatment (average length of data collection = 4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.	From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.
Overall Survival	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.	From study entry to death or last contact, up to 5 years of follow-up.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Gynecologic Oncology Group

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: November 9, 2004
• First Submitted That Met QC Criteria: November 8, 2004
• First Posted (Estimate): November 9, 2004

Study Record Updates

• Last Update Posted (Actual): July 24, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Disease Attributes; Carcinoma; Recurrence; Endometrial Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Epothilones; Epothilone B
• Other Study ID Numbers: NCI-2012-02628 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA027469 (U.S. NIH Grant/Contract); CDR0000391849; GOG-0129P (Other Identifier: CTEP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No