Edotecarin in Treating Women With Locally Advanced or Metastatic Breast Cancer That Has Not Responded to Chemotherapy

A Phase II Study of Intravenous Edotecarin (PHA-782615) in Patients With Anthracycline- and Taxane-Refractory or Chemoresistant Metastatic Breast Cancer

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

PURPOSE: This phase II trial is studying how well edotecarin works in treating women with locally advanced or metastatic breast cancer that has not responded to previous chemotherapy.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: edotecarin

Detailed Description

OBJECTIVES:

Primary

• Determine the antitumor activity of edotecarin in women with anthracycline- and taxane-refractory or chemoresistant locally advanced or metastatic breast cancer.

Secondary

• Determine the time to tumor response and duration of response in patients treated with this drug.
• Determine the overall survival of patients treated with this drug.
• Determine the clinical benefit of this drug in these patients.
• Determine the safety and tolerability of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is an open-label, multicenter study.

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

Patients are followed every 2 months until disease progression.

PROJECTED ACCRUAL: A total of 31-65 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary adenocarcinoma of the breast

  • Locally advanced or metastatic disease
• Not amenable to surgery or radiotherapy with curative intent

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques OR 10 mm by CT scan
  • Not previously irradiated

• Meets 1 of the following criteria:

  • Previously treated with anthracycline and concurrent or sequential taxane therapy

    • Refractory to the most recent taxane-based chemotherapy, defined as 1 of the following:

      • Progressive disease during therapy or within 4 months of the last dose with or without documented response for advanced disease
      • Progressive disease within 6 months of completing taxane-based chemotherapy as neoadjuvant therapy
  • Resistant to prior chemotherapy, as defined by progressive disease within 6 months of completing prior chemotherapy for advanced disease
• No known brain metastases or carcinomatous meningitis* NOTE: *Baseline CT scan or MRI of the brain required if there is clinical suspicion of CNS metastases
• No spinal cord compression

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 2.5 times ULN (5 times ULN if liver involvement secondary to tumor is present)
• Albumin at least 3.0 g/dL

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• LVEF at least 50% or ULN by echocardiogram or MUGA

• None of the following within the past 6 months:

  • Myocardial infarction
  • Severe or unstable angina
  • Symptomatic congestive heart failure
  • Cerebrovascular accident or transient ischemic attack
  • Deep vein thrombosis or other significant thromboembolic event
• No ongoing cardiac dysrhythmias grade 2 or greater
• No atrial fibrillation of any grade

Pulmonary

• No pulmonary embolism within the past 6 months

Gastrointestinal

• No active inflammatory bowel disease
• No partial or complete bowel obstruction
• No chronic diarrhea

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known HIV positivity
• No active infection
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation or confound study results

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent biological response modifiers
• No concurrent immunotherapy
• No concurrent sargramostim (GM-CSF)
• No other concurrent granulocyte colony-stimulating factors

Chemotherapy

• See Disease Characteristics
• Prior adjuvant chemotherapy allowed
• No prior topoisomerase I inhibitors
• No more than 2 prior chemotherapy regimens for advanced disease
• No prior high-dose chemotherapy that required hematopoietic stem cell rescue
• No other concurrent chemotherapy

Endocrine therapy

• Prior adjuvant hormonal therapy or hormonal therapy for advanced/metastatic disease allowed provided that therapy is discontinued before study entry
• No concurrent hormonal therapy

Radiotherapy

• See Disease Characteristics
• No prior radiotherapy to more than 25% of the bone marrow

• No concurrent radiotherapy during and for 5 days after study treatment

  • Palliative radiotherapy allowed provided no more than 20% of the bone marrow is involved

Surgery

• No coronary/peripheral artery bypass graft within the past 6 months

Other

• Recovered from prior therapy (except alopecia or neurotoxicity)
• At least 4 weeks since any other prior therapy
• More than 4 weeks since prior investigational agents
• No concurrent enrollment on another clinical trial
• No other concurrent approved or investigational anticancer treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Andrew D. Seidman, MD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (ACTUAL): April 1, 2006
• Study Completion (ACTUAL): December 1, 2009

Study Registration Dates

• First Submitted: October 3, 2003
• First Submitted That Met QC Criteria: October 6, 2003
• First Posted (ESTIMATE): October 7, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): December 19, 2013
• Last Update Submitted That Met QC Criteria: December 18, 2013
• Last Verified: December 1, 2009

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
• Other Study ID Numbers: CDR0000329917; MSKCC-03056; PHARMACIA-EDOABC-4439-001