GTI-2040 and Capecitabine in Treating Patients With Metastatic Breast Cancer

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Male Breast Cancer

Recurrent Breast Cancer

Stage IV Breast Cancer

Treatments

Biological: GTI-2040

Drug: capecitabine

Study type

Interventional

Funder types

NIH

Identifiers

NCT00068588

CDR0000327757 (Registry Identifier)

N01CM62209 (U.S. NIH Grant/Contract)

NCI-2012-02827

PHII-46

Details and patient eligibility

About

This phase II trial is studying how well giving GTI-2040 together with capecitabine works in treating patients with metastatic breast cancer. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. GTI-2040 may help capecitabine kill more tumor cells by making them more sensitive to the drug

Full description

PRIMARY OBJECTIVES:

I. To evaluate the response rate and response duration to combination therapy with GTI-2040 and capecitabine in the treatment of metastatic breast cancer.

II. To safely evaluate the toxicity of this drug combination and schedule in this patient population by first using a lower dose followed by escalation.

III. To determine pharmacokinetic data on plasma levels of GTI-2040 in this patient population.

IV. To investigate potential molecular markers of ribonucleotide reductase inhibition and fluoropyrimidine metabolism in this patient population treated with the combination of GTI-2040 and capecitabine.

OUTLINE: This is a multicenter study.

Patients receive GTI-2040 IV continuously on days 1-15 of the first course and days 1-14 of all subsequent courses. Patients also receive oral capecitabine twice daily on days 2-15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Enrollment

24 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients must have histologically or cytologically confirmed metastatic adenocarcinoma of the breast
Patients must have measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
Patients must have progressed on at least one but no more than two prior chemotherapy regimens for metastatic disease; patients must not have received prior capecitabine or 5-fluorouracil; patients with hormone-sensitive tumors should have received hormone treatment and any prior number of hormonal agents will be allowed; patients with tumors that overexpress HER-2/neu (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization) should have received herceptin, either in the adjuvant or metastatic setting, unless there is a contraindication to herceptin therapy; all prior therapies must have been completed 4 weeks before treatment
Life expectancy of greater than 3 months
ECOG performance status =< 2 (Karnofsky >= 50%)
Leukocytes >= 3,000/μL
Absolute neutrophil count >= 1,500/μL
Platelets >= 100,000/μL
Total bilirubin within normal institutional limits
AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min
Patients must have completed radiation treatment > 4 weeks prior to study entry; previously radiated area(s) must not be the only site of disease
All major surgical procedures must be completed > 4 weeks prior to study entry; placement of vascular access device or tissue biopsy will not be considered major surgery
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Ability to understand and the willingness to sign a written informed consent document
Patients must agree to the placement of a central venous catheter in order to receive the continuous infusion treatment

Exclusion criteria

Patients with only non-measurable disease, defined as all other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions, which include the following:
- bone lesions
- leptomeningeal disease
- ascites
- pleural/pericardial effusion
- inflammatory breast disease
- lymphangitis cutis/pulmonis
- abdominal masses that are not confirmed and followed by imaging techniques
- cystic lesions
Patients who have had chemotherapy, hormone therapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Patients may not be receiving any other investigational agents; patients may not have received prior GTI-2040
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
History of allergic reactions attributed to compounds of similar chemical or biologic composition to GTI-2040 or to capecitabine or 5-fluorouracil
Patients requiring anticoagulant therapy; low-dose anticoagulant (warfarin 1 mg per day) for the primary prophylaxis of venous catheter-associated thrombosis is permitted
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant women are excluded from this study because GTI-2040 and capecitabine have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GTI-2040 and capecitabine, breastfeeding should be discontinued if the mother is treated
Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with GTI-2040 or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated