Irinotecan and Etoposide in Treating Patients With Recurrent, Locally Advanced, or Metastatic Breast Cancer

A Phase II Study: Irinotecan and Etoposide as Treatment for Refractory, Metastatic Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as irinotecan and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving irinotecan together with etoposide works in treating patients with recurrent, locally advanced, or metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Etoposide; Drug: Irinotecan hydrochloride

Detailed Description

OBJECTIVES:

Primary

• To determine the response rate, as assessed by RECIST criteria, in patients with recurrent locally advanced or metastatic breast cancer treated with irinotecan hydrochloride and etoposide after prior exposure to anthracycline, taxane, and capecitabine therapy.

Secondary

• To determine the median time to progression in these patients.
• To determine the response duration and survival in these patients.
• To measure the type and rate of grade 3 or greater toxicity of this treatment regimen in these patients.

OUTLINE: Patients receive irinotecan hydrochloride IV on days 1 and 15 and oral etoposide on days 1-14. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

After completion of study therapy, patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center at University of Arizona Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 120 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of locally advanced or metastatic breast cancer

  • Recurrent, refractory or progressive disease after receiving prior anthracycline, taxane, and capecitabine therapy

    • Prior anthracycline and taxane therapy may have been as neoadjuvant, or adjuvant therapy if disease progression is documented within a year of completing that agent
    • Received prior capecitabine therapy for metastatic or recurrent disease

• Measurable disease

  • Bone metastases requires other disease present that can be measured
• No brain metastases, unless documented to be controlled post-completion of local therapy (surgery and/or radiation therapy) for at least 4 weeks
• No meningeal carcinomatosis
• No malignant effusion as the only site of disease recurrence
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• Performance status of 0-2
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 40 mL/min
• Hemoglobin ≥ 10 g/dL
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin normal or hyperbilirubinemia < grade 1 (unless due to Gilbert syndrome with elevated total but normal levels of conjugated bilirubin)
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other non-breast malignancy, except nonmelanoma skin cancer
• No other serious underlying medical condition, that in the opinion of the treating physician, would make study protocol unreasonably hazardous for the patient or would preclude the patient's ability to comply with the study protocol

PRIOR CONCURRENT THERAPY:

• See Disease Characteristic
• Recovered from all prior chemotherapy or radiotherapy to NCI CTC grade ≤ 1
• Unlimited documented prior chemotherapy regimens allowed
• No prior irinotecan hydrochloride or etoposide
• No Hypericum perforatum (St. John's wort) 14 days prior to, during, or 7 days after completion of study therapy
• At least 7 days since prior and no concurrent phenytoin, carbamazepine, phenobarbital, or any other enzyme-inducing anticonvulsant drug (EIACD)
• No concurrent aprepitant

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: Etoposide and Irinotecan hydrochloride; Irinotecan 100 mg/m2 IV days 1 and 15. Etoposide 50 mg PO x14 days followed by 2 weeks off.	Drug: Etoposide; 50 mg PO x14 days followed by 2 weeks off, 28 day/Cycle; Other Names: Vepesid; Drug: Irinotecan hydrochloride; Irinotecan 100 mg/m2 IV days 1 and 15, 28 day/Cycle; Other Names: Irinotecan hydrochloride trihydrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time to Progression	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	Measured time from the start of treatment to the time the patient is first recorded as having disease progression or dies. If no progression or death while being followed via tumor assessment, censored at last date known alive, assesed up to 13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Still alive for a certain period of time after they were diagnosed with or started treatment	Measured from the start of protocol therapy until the date of death from any cause or will be censored at the date the patient was last known to be alive, assesed up to 13 months

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Robert B. Livingston, MD, University of Arizona

Publications and helpful links

General Publications

• Segar JM, Reed D, Stopeck A, Livingston RB, Chalasani P. A Phase II Study of Irinotecan and Etoposide as Treatment for Refractory Metastatic Breast Cancer. Oncologist. 2019 Dec;24(12):1512-e1267. doi: 10.1634/theoncologist.2019-0516. Epub 2019 Aug 5.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: June 6, 2008
• First Submitted That Met QC Criteria: June 6, 2008
• First Posted (Estimate): June 9, 2008

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: October 15, 2015
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: stage IV breast cancer; stage IIIA breast cancer; recurrent breast cancer; stage IIIB breast cancer; stage IIIC breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Etoposide; Irinotecan
• Other Study ID Numbers: 07-0327-04; P30CA016672 (U.S. NIH Grant/Contract); UARIZ-BIO07046 (Other Identifier: University of Arizona); UARIZ-143 (Other Identifier: University of Arizona); PFIZER-GA59608L (Other Grant/Funding Number: Pfizer); UARIZ-P18089 (Other Identifier: University of Arizona)