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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00068588
First received: September 10, 2003
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Male Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Biological: GTI-2040
Drug: capecitabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of GTI-2040 (NSC 722929) in Combination With Capecitabine in Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate of a combination of GTI-2040 and capecitabine [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Maximum tolerated dose determined by dose-limiting toxicities [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Duration of time from start of treatment to time of progression, assessed up to 6 years ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: October 2003
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (GTI-2040, capecitabine)
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.
Biological: GTI-2040
Given IV
Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00068588

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Helen Chew Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00068588     History of Changes
Other Study ID Numbers: NCI-2012-02827, PHII-46, N01CM62209, CDR0000327757
Study First Received: September 10, 2003
Last Updated: January 25, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Fluorouracil
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 29, 2014