Oblimersen Plus Doxorubicin and Docetaxel in Treating Patients With Metastatic or Locally Advanced Breast Cancer

NCT ID: NCT00063934

Last Updated: 2019-03-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-05-31
• Study Completion Date: 2008-02-29

Brief Summary

This phase I/II trial is studying the side effects and best dose of oblimersen when given together with doxorubicin and docetaxel and to see how well they work in treating women with metastatic or locally advanced breast cancer. Drugs used in chemotherapy, such as doxorubicin and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of doxorubicin and docetaxel by making the tumor cells more sensitive to the drugs.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the pharmacokinetics of G3139, doxorubicin and docetaxel in breast cancer patients receiving G3139/AT therapy. (Phase I) II. To determine the safety of bcl-2 antisense oligonucleotide G3139 (GenasenseTM) together with docetaxel plus doxorubicin (AT) in patients with metastatic and locally advanced breast cancer (LABC). (Phase I) III. To determine the therapeutic efficacy of neoadjuvant G3139 in combination with AT chemotherapy in patients with LABC. (Phase II) IV. To further evaluate the safety of bcl-2 antisense oligonucleotide G3139 (GenasenseTM) together with docetaxel plus doxorubicin (AT) in patients with locally advanced breast cancer (LABC). (Phase II)

SECONDARY OBJECTIVES:

I. To determine the clinical and imaging response to neoadjuvant G3139/AT in the breast and the axillary lymph nodes. (Phase II) II. To determine the disease-free survival of breast cancer patients treated with neoadjuvant G3139/AT. (Phase II) III. To further define the pharmacokinetics of G3139/AT. (Phase II) IV. To evaluate the role of Bcl-2 expression as a predictor of response to neoadjuvant G3139/AT therapy. (Phase II) V. To obtain serial breast cancer samples from patients treated with G3139. (Phase II)

OUTLINE: This is an open-label, dose-escalation study of oblimersen.

PHASE I (COMPLETED AS OF 8/16/04): Patients receive oblimersen IV continuously on days 1-6 interrupted only to administer doxorubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 6. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 7-13 or pegfilgrastim SC on day 7. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive doxorubicin, docetaxel, G-CSF or pegfilgrastim, and oblimersen at the MTD as in phase I.

Patients with resectable tumors after 6 courses undergo surgical resection.

Patients are followed every 3-6 months for 5 years.

Conditions

Male Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (oblimersen, doxorubicin, docetaxel)

PHASE I (COMPLETED AS OF 8/16/04): Patients receive oblimersen IV continuously on days 1-6 interrupted only to administer doxorubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 6. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 7-13 or pegfilgrastim SC on day 7. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive doxorubicin, docetaxel, G-CSF or pegfilgrastim, and oblimersen at the MTD as in phase I.

Patients with resectable tumors after 6 courses undergo surgical resection.

Group Type: EXPERIMENTAL

oblimersen sodium

Intervention Type: BIOLOGICAL

Given IV

doxorubicin hydrochloride

Intervention Type: DRUG

Given IV

docetaxel

Intervention Type: DRUG

Given IV

filgrastim

Intervention Type: BIOLOGICAL

Given SC

pegfilgrastim

Intervention Type: BIOLOGICAL

Given SC

therapeutic conventional surgery

Intervention Type: PROCEDURE

Undergo surgical resection

pharmacological study

Intervention Type: OTHER

Optional correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Optional correlative studies

Interventions

oblimersen sodium

Given IV

Intervention Type: BIOLOGICAL

doxorubicin hydrochloride

Given IV

Intervention Type: DRUG

docetaxel

Given IV

Intervention Type: DRUG

filgrastim

Given SC

Intervention Type: BIOLOGICAL

pegfilgrastim

Given SC

Intervention Type: BIOLOGICAL

therapeutic conventional surgery

Undergo surgical resection

Intervention Type: PROCEDURE

pharmacological study

Optional correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

Optional correlative studies

Intervention Type: OTHER

Other Intervention Names

augmerosen; G3139; G3139 bcl-2 antisense oligodeoxynucleotide; Genasense; ADM; ADR; Adria; Adriamycin PFS; Adriamycin RDF; RP 56976; Taxotere; TXT; G-CSF; Neupogen; Filgrastim SD-01; GCSF-SD01; Neulasta; SD-01 sustained duration G-CSF; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• PHASE I: Patients must have histologically or cytologically confirmed breast cancer
• PHASE I: To be eligible for the phase I component of this study, patients must have stage IIIB, IIIC or IV breast cancer; these include patients with T4, any N, M0; any T, N3, M0; any T, any N, M1
• PHASE I: Measurable disease is not required for patients participating in the phase I component
• PHASE I: Prior G3139, taxane or anthracycline therapy is not allowed
• PHASE I: Patients may have received up to 3 prior chemotherapy regimens for breast cancer (excluding anthracyclines and taxanes), either as adjuvant/neoadjuvant therapy or for metastatic disease
• PHASE I: Life expectancy of greater than 6 months
• PHASE I: ECOG performance status =< 2 (Karnofsky >= 60%)
• PHASE I: Leukocytes >= 3,000/L
• PHASE I: Absolute neutrophil count >= 1,500/L
• PHASE I: Platelets >= 100,000/L
• PHASE I: Total bilirubin =< 1.5 mg/dl
• PHASE I: ALT(SGPT) =< 2.5 X upper limit of normal
• PHASE I: Creatinine =< 2.0 mg/dl
• PHASE I: Normal cardiac function (LVEF >= 45%) as documented by MUGA scan and/or echocardiogram
• PHASE I: The effects of G3139 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because anthracycline and taxanes used in this trial are known to be teratogenic, 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
• PHASE I: Ability to understand and the willingness to sign a written informed consent document
• PHASE II: Patients must have histologically or cytologically confirmed breast cancer
• PHASE II: Patients must have stage IIIA, IIIB, or IIIC breast cancer; these include patients with T4, any N, M0; any T, N2-3, M0; T3, N1, M0; patients with ipsilateral supraclavicular lymph node metastases (IIIC) are eligible; patients with evidence of distant metastases (stage IV) are not eligible
• PHASE II: Measurable disease is required; disease will be measured prior to initiation of G3139/doxorubicin/docetaxel therapy by physical exam, mammography and ultrasound of the affected areas; pathologic response will be measured at the time of definitive surgery
• PHASE II: Prior G3139 therapy is not allowed
• PHASE II: Prior chemotherapy, hormone therapy, definitive surgery, or radiation therapy for breast cancer are not allowed
• PHASE II: Life expectancy of greater than 6 months
• PHASE II: ECOG performance status =< 2 (Karnofsky >= 60%)
• PHASE II: Leukocytes >= 3,000/L
• PHASE II: Absolute neutrophil count >= 1,500/L
• PHASE II: Platelets >= 100,000/L
• PHASE II: Total bilirubin =< 1.5 mg/dl
• PHASE II: ALT(SGPT) =< 2.5 X upper limit of normal
• PHASE II: Creatinine =< 2.0 mg/dl
• PHASE II: Normal cardiac function (LVEF >= 45%) as documented by MUGA scan and/or echocardiogram
• PHASE II: The effects of G3139 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because anthracycline and taxanes used in this trial are known to be teratogenic, 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
• PHASE II: Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• PHASE I: Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the phase I study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• PHASE I: Patients may not be receiving any other investigational agents
• PHASE I: 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
• PHASE I: Leptomeningeal disease
• PHASE I: Symptomatic lymphangitic pulmonary metastases
• PHASE I: History of allergic reactions attributed to compounds of similar chemical or biologic composition to G3139 or other agents used in the study; patients are excluded if known hypersensitivity to drugs formulated in polysorbate 80 (Tween 80)
• PHASE I: 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
• PHASE I: Patients with neuropathy grade 2 or higher
• PHASE I: Pregnant women are excluded from this study because G3139 is an oligonucleotide agent with 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 G3139, breastfeeding should be discontinued if the mother is treated with G3139; these potential risks may also apply to other agents used in this study, such as doxorubicin and docetaxel
• PHASE II: Patients may not be receiving any other investigational agents
• PHASE II: History of allergic reactions attributed to compounds of similar chemical or biologic composition to G3139 or other agents used in the study; patients are excluded if known hypersensitivity to drugs formulated in polysorbate 80 (Tween 80)
• PHASE II: 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
• PHASE II: Patients with neuropathy grade 2 or higher
• PHASE II: Pregnant women are excluded from this study because G3139 is an oligonucleotide agent with 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 G3139, breastfeeding should be discontinued if the mother is treated with G3139; these potential risks may also apply to other agents used in this study, such as doxorubicin and docetaxel

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francisco Esteva

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

NCI-2012-02885

Identifier Type: REGISTRY

Identifier Source: secondary_id

6023

Identifier Type: -

Identifier Source: secondary_id

DM02-700

Identifier Type: OTHER

Identifier Source: secondary_id

6023

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM17003

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02885

Identifier Type: -

Identifier Source: org_study_id