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

Stage IV Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00095888
• Other study ID #: NCI-2012-02632
• Secondary ID: MC0333N01CM62205
• Status: Terminated
• Phase: Phase 2
• First received: November 9, 2004
• Last updated: January 15, 2013
• Start date: October 2004

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 68
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• Male Breast Cancer
• Recurrent Breast Cancer
• Stage IV Breast Cancer

Intervention

Drug:
• triapine
Given IV
• gemcitabine hydrochloride
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0		Up to 3 years	Yes
Secondary	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	No
Secondary	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	No
Secondary	Changes in tyrosyl radical and cell-cycle arrest on buccal mucosa		Pre-infusion, 2 and 4.5 hours post-infusion	No
Secondary	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	No
Secondary	MDR polymorphism on tumor tissue		Baseline	No