3-AP and Gemcitabine in Treating Patients With Refractory Metastatic Breast Cancer

A Phase II Trial Of Gemcitabine And Triapine In Refractory Metastatic Breast Cancer

Phase II trial to study the effectiveness of combining 3-AP with gemcitabine in treating patients who have refractory metastatic breast cancer. Drugs used in chemotherapy, such as 3-AP and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining 3-AP with gemcitabine may kill more tumor cells

Study Overview

• Status: Terminated
• Conditions: Male Breast Cancer; Stage IV Breast Cancer; Recurrent Breast Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: triapine; Other: pharmacological study; Drug: gemcitabine hydrochloride

Detailed Description

OBJECTIVES: Primary I. Determine antitumor activity of 3-AP (Triapine®) and gemcitabine by measuring tumor size in patients with refractory metastatic breast cancer.

Secondary I. Determine the safety and tolerability of this regimen in these patients. II. Determine the time to disease progression in patients treated with this regimen.

III. Determine the effect of multidrug resistance polymorphisms on pharmacokinetics and toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive 3-AP (Triapine®) IV over 2 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after registration.

PROJECTED ACCRUAL: A total of 30-75 patients will be accrued for this study within 24 months.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed breast cancer

  • Refractory metastatic disease

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Must have received 1, and only 1, prior chemotherapy regimen for metastatic disease
• Patients overexpressing HER2/neu antigen must have received a prior trastuzumab (Herceptin®)-containing regimen
• No known brain metastases

• Hormone receptor status:

  • Not specified
• Male or female
• Performance status - ECOG 0-2
• At least 12 weeks
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine normal
• Creatinine clearance ≥ 60 mL/min
• No uncontrolled congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No severe pulmonary disease requiring oxygen
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No glucose-6-phosphate dehydrogenase (G6PD) deficiency
• No other uncontrolled illness
• No active or ongoing infection
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to 3-AP (Triapine®) or other study agents
• No psychiatric illness or social situation that would preclude study compliance
• No other malignancy within the past 5 years
• See Disease Characteristics
• No concurrent immunotherapy
• No concurrent routine colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])
• See Disease Characteristics
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No prior gemcitabine for metastatic disease
• No other concurrent chemotherapy
• More than 4 weeks since prior hormonal therapy
• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy
• Recovered from prior therapy
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent investigational 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 (triapine, gemcitabine hydrochloride); Patients receive 3-AP (Triapine®) IV over 2 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: triapine; Given IV; Other Names: 3-AP; OCX-191; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: gemcitabine hydrochloride; Given IV; Other Names: Gemzar; gemcitabine; dFdC; difluorodeoxycytidine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed response (complete or partial response)	Ninety five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The distribution of overall survival will be estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 3 years
Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0		Up to 3 years
Time to progression	The distribution of time to progression will be estimated using the method of Kaplan-Meier.	Time from registration to the time of progression, assessed up to 3 years
Changes in tyrosyl radical and cell-cycle arrest on buccal mucosa		Pre-infusion, 2 and 4.5 hours post-infusion
Changes in R2 messenger ribonucleic acid (mRNA) on protein levels before and after treatment with triapine		Pre-infusion, 2 and 4.5 hours post-infusion
MDR polymorphism on tumor tissue		Baseline

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: James Stewart, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): June 1, 2006

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 (Estimate): January 16, 2013
• Last Update Submitted That Met QC Criteria: January 15, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Breast Neoplasms, Male; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: NCI-2012-02632; N01CM62205 (U.S. NIH Grant/Contract); MC0333