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Male Breast CancerPhase 1/2NCT00063934

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

A Phase 1/2 study testing oblimersen sodium, doxorubicin hydrochloride and docetaxel in people with Male Breast Cancer and Stage IIIA Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
oblimersen sodium, doxorubicin hydrochloride and docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
May 2003to Feb 2008
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase 1/2 Study of Bcl-2 Antisense Oligonucleotide G3139 in Combination With Doxorubicin and Docetaxel in Metastatic and Locally Advanced Breast Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Medical subject headings
Breast Neoplasms, Male, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • oblimersen sodiumBiological

    Also called augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense

    Given IV

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

  • docetaxelDrug

    Also called RP 56976, Taxotere, TXT

    Given IV

  • filgrastimBiological

    Also called G-CSF, Neupogen

    Given SC

  • pegfilgrastimBiological

    Also called Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF

    Given SC

  • therapeutic conventional surgeryProcedure or surgery

    Undergo surgical resection

  • pharmacological studyOther

    Also called pharmacological studies

    Optional correlative studies

  • laboratory biomarker analysisOther

    Optional correlative studies

Study groups in NCT00063934
Study groupRoleWhat they receive
Treatment (oblimersen, doxorubicin, docetaxel)ExperimentalPHASE 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.
Receives: Biological: oblimersen sodium; Drug: doxorubicin hydrochloride; Drug: docetaxel; Biological: filgrastim; Biological: pegfilgrastim; Procedure: therapeutic conventional surgery; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participant With Toxicities

    Measured: From baseline until the date of first documented toxicity or date of death from any cause, whichever came first, assessed every three weeks up to 2 years and 5 months

  2. Number of Participants With Pathologic Complete Response (pCR)

    Pathologic complete responses (pCR), defined as no evidence of residual invasive tumor, including no residual tumor in the axillary lymph nodes, measured by microscopic evaluation of tissue specimen at time of definitive surgery (after 6 courses of neoadjuvant therapy). Neoadjuvant (preoperative) therapy administered on the first five days of every 3-week cycle. Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]

    Measured: At time of definitive surgery (after 6 courses of neoadjuvant therapy in 3 week cycles), approximately 18 weeks

Secondary outcomes (2)

  1. Clinical Imaging Responses

    Evaluation target lesions (clinical response) by physical exam/ultrasound measurements of primary tumor and axillary lymph nodes after 3-6 courses: Complete Response: Disappearance of all target lesions; Partial Response: >30% decrease in sum longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease: >20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1>new lesions; Stable Disease: Neither sufficient shrinkage for PR nor increase for PD, reference smallest sum LD since treatment started.

    Measured: After 3 and 6 courses of 21 day treatments (up to 18 weeks)

  2. Bcl-2 Expression in Breast Cancer Tissue

    Number of participant with Bcl-2 Expression in breast cancer tissue by protein and mRNA expression before treatment and at 3-5 days after oblimersen treatment.

    Measured: before treatment and at 3-5 days after oblimersen treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jul 2003 (estimated)
  2. Study startMay 2003
  3. Primary completionFeb 2008
  4. Study completionFeb 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00063934
Sponsor's protocol ID
NCI-2012-02885
Other IDs
NCI-2012-02885, 6023, DM02-700, 6023, P30CA016672, N01CM17003
Status last verified
Feb 2019
First submitted
8 Jul 2003
Last updated
5 Mar 2019

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing oblimersen sodium, doxorubicin hydrochloride and docetaxel in people with Male Breast Cancer and Stage IIIA Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participant With Toxicities (time frame: From baseline until the date of first documented toxicity or date of death from any cause, whichever came first, assessed every three weeks up to 2 years and 5 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00063934.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2019.

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