Brostallicin and Cisplatin in Treating Patients With Metastatic Breast Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Triple-negative Breast Cancer

Treatments: Drug: brostallicin; Drug: cisplatin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01091454

CDR0000665441 (Registry Identifier)

NCCTG-N0937

NCI-2011-02016 (Registry Identifier)

N0937

Details and patient eligibility

About

This phase II trial studies how well brostallicin and cisplatin work in treating patients with breast cancer that has spread to other parts of the body (metastatic) and does not have estrogen receptors, progesterone receptors, or large amounts of human epidermal growth factor receptor 2 (HER2) on its cells (triple-negative). Drugs used in chemotherapy, such as brostallicin and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from spreading.

Full description

PRIMARY OBJECTIVES:

I. To identify any clinical efficacy of brostallicin and cisplatin in the treatment of breast cancer patients having a triple negative (estrogen receptor [ER]/progesterone receptor [PR]/HER2 negative) phenotype, as measured by progression-free survival (PFS) at 3 months.

SECONDARY OBJECTIVES:

I. To describe the confirmed tumor response rate of patients with measurable disease receiving brostallicin and cisplatin.

II. To describe the duration of response in patients with measurable disease receiving brostallicin and cisplatin.

III. To describe the 6-month progression-free survival of patients receiving brostallicin and cisplatin.

IV. To describe the overall survival (OS) of patients receiving brostallicin and cisplatin.

V. To evaluate the adverse event profile of the study regimen (adverse events graded using the Cancer Therapy Evaluation Program [CTEP] Active Version of the Common Terminology Criteria for Adverse Events [CTCAE]).

OUTLINE:

Patients receive cisplatin intravenously (IV) over 2 hours on day 1 and brostallicin IV over 10 minutes on day 2. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months until disease progression and then every 6 months for up to 5 years.

Enrollment: 48 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the breast with clinical evidence of metastatic disease
• Triple negative breast cancer defined as HER2-(according to current American Society of Clinical Oncology [ASCO] College of American Pathologists [CAP] guidelines), ER- (defined as =< 1% by IHC) and PgR- (defined as =< 1% by IHC)
• 0 to 4 prior chemotherapy regimens in the metastatic setting
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• Hemoglobin >= 10.0 g/dL
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelet count >= 100,000/mL
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Serum creatinine =< 1.5 mg/dL
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN or SGOT (AST) and SGPT (ALT) =< 5 x ULN if elevations are due to liver metastases
• Alkaline phosphatase =< 2.5 x ULN or alkaline phosphatase =< 5 x ULN if elevations are due to liver metastases
• Electrocardiogram (EKG) completed =< 15 days prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
• Life expectancy > 3 months
• Has written informed consent
• Willingness to return to NCCTG enrolling institution for treatment and follow-up
• Patient willing to provide blood samples for research purposes

Exclusion Criteria

• HER2 positive (3+ by IHC or fluorescence in situ hybridization [FISH] amplified) breast cancer by ASCO/CAP guidelines

• Estrogen receptor (ER) and/or progesterone receptor (PR/PgR) positive breast cancer (defined as > 1% of either receptor by IHC)

• Any of the following

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception (as determined by the treating physician) while on this study and for 30 days after end of treatment with the study drugs

• Stage III or IV invasive non-breast malignancy in =< 5 years prior to registration

• Pre-existing peripheral neuropathy of grade >= 2 (using the CTEP active version of the CTCAE)

• Major surgery =< 4 weeks prior to registration

• Chemotherapy or immunologic therapy =< 3 weeks prior to registration

• Radiotherapy =< 2 weeks prior to registration, except if to a non-target lesion only

  * NOTES:

  • Prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed
  • If patient receives single dose radiation for palliation or radiation to non-target lesion, they may immediately proceed to registration without waiting 2 weeks
  • Acute adverse events from radiation must have resolved to =< grade 1 (according to the CTEP active version of the CTCAE)

• Evidence of active brain metastasis including leptomeningeal involvement

  * NOTE: Central nervous system (CNS) metastasis controlled by prior surgery and/or radiotherapy is allowed; to be considered controlled, there must be at least 2 months of no symptoms or evidence of progression prior to study entry and corticosteroid therapy given to control brain edema must have been discontinued

• History of allergy or hypersensitivity to the drugs used in this study (or their excipients) including platinum compounds (cisplatin, carboplatin)

• Active, unresolved infection

• Uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations or co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or would interfere significantly with the proper assessment of safety of the prescribed regimens or would limit compliance with study requirements or would make it undesirable for patient to participate in the trial

• Clinically significant cardiovascular or cerebrovascular disease, including any history of the following =< 6 months prior to registration:

  • Myocardial infarction
  • Unstable angina
  • New York Heart Association (NYHA) class II or greater congestive heart failure
  • Uncontrolled or clinically significant cardiac arrhythmia (patients with controlled atrial fibrillation are eligible)

• Currently receiving treatment in a different clinical study in which investigational procedures are performed or investigational therapies are administered

  * NOTE: Patient may not enroll in such clinical trials while participating in this study; exception may be granted for trials related to symptom management (cancer control) which do not employ hormonal treatments or treatments that may block the path of the targeted agents used in this trial

• Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive with an acquired immune deficiency syndrome (AIDS)-defining illness; HIV positive patients with cluster of differentiation (CD)4 count within institutional normal range and no history of an AIDS-defining illness are eligible

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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48 participants in 1 patient group

Treatment (cisplatin and brostallicin)

Experimental group

Description:

Patients receive cisplatin IV over 2 hours on day 1 and brostallicin IV over 10 minutes on day 2. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: brostallicin

Drug: cisplatin