Clinical Trials /

Cisplatin With or Without Veliparib in Treating Patients With Recurrent or Metastatic Triple-Negative and/or BRCA Mutation-Associated Breast Cancer With or Without Brain Metastases

NCT02595905

Description:

This randomized phase II trial studies how well cisplatin works with or without veliparib in treating patients with triple-negative breast cancer and/or BRCA mutation-associated breast cancer that has come back or has or has not spread to the brain. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if cisplatin is more effective with or without veliparib in treating patients with triple-negative and/or BRCA mutation-associated breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Cisplatin</span> With or Without <span class="go-doc-concept go-doc-intervention">Veliparib</span> in Treating Patients With Stage IV <span class="go-doc-concept go-doc-keyword">Triple-Negative</span> and/or BRCA <span class="go-doc-concept go-doc-keyword">Mutation</span>-Associated Breast Cancer

Title

  • Brief Title: Cisplatin With or Without Veliparib in Treating Patients With Stage IV Triple-Negative and/or BRCA Mutation-Associated Breast Cancer
  • Official Title: Phase II Randomized Placebo-Controlled Trial of Cisplatin With or Without ABT-888 (Veliparib) in Metastatic Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02595905

    ORG ID: NCI-2015-01912

    NCI ID: NCI-2015-01912

    Trial Conditions

    BRCA1 Mutation Carrier

    BRCA2 Mutation Carrier

    Estrogen Receptor Negative

    HER2/Neu Negative

    Progesterone Receptor Negative

    Stage IV Breast Cancer

    Triple-Negative Breast Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    Cisplatin Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin Arm I (cisplatin and placebo), Arm II (cisplatin and veliparib)
    Veliparib ABT-888, PARP-1 inhibitor ABT-888 Arm II (cisplatin and veliparib)

    Trial Purpose

    This randomized phase II trial studies how well cisplatin works with or without veliparib in
    treating patients with stage IV triple-negative breast cancer and/or breast cancer (BRCA)
    mutation-associated breast cancer. Drugs used in chemotherapy, such as cisplatin, work in
    different ways to stop the growth of tumor cells, either by killing the cells, by stopping
    them from dividing, or by stopping them from spreading. Veliparib may stop the growth of
    tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if
    cisplatin is more effective with or without veliparib in treating patients with
    triple-negative and/or BRCA mutation-associated breast cancer.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To compare the efficacy of cisplatin with or without ABT-888 (veliparib) on
    progression-free survival (PFS) in each of the following groups: patients with germline BRCA
    (gBRCA) mutation-associated breast cancer, patients with germline BRCA wild-type breast
    cancer who have evidence of BRCAness phenotype, and patients with germline BRCA wild-type
    breast cancer who do not have evidence of BRCAness phenotype.

    SECONDARY OBJECTIVES:

    I. For patients with gBRCA mutation associated breast cancer or triple-negative breast
    cancer (TNBC) with or without BRCAness phenotype, compare the efficacy of cisplatin with or
    without ABT-888 on overall survival (OS), response rate, and clinical benefit rate.

    II. Compare the differential benefit of ABT-888 across the three groups using both PFS and
    OS as outcomes.

    III. Compare toxicities of ABT-888 to placebo in each of the three groups separately.

    TERTIARY OBJECTIVES:

    I. To evaluate the impact of homologous recombination deficiency score (independent of other
    BRCAness markers) on response rate (RR) and PFS in patients treated with chemotherapy versus
    chemotherapy plus ABT-888.

    II. To evaluate the overlap among various markers utilized to define the BRCAness phenotype.

    III. To evaluate the impact of prediction analysis of microarray 50 (PAM50) basal signature
    (independent of gBRCA status and other BRCAness markers) on RR and PFS in patients treated
    with chemotherapy versus chemotherapy plus ABT-888.

    IV. To evaluate the impact of BRCA1 mRNA expression (independent of gBRCA status and other
    BRCAness markers) on response rate (RR) and PFS in patients treated with chemotherapy versus
    chemotherapy plus ABT-888.

    OUTLINE: Patients are randomized to 1 of 2 treatment arms.

    ARM I: Patients receive cisplatin intravenously (IV) over 1 hour on day 1 and placebo orally
    (PO) twice daily (BID) on days 1-14. Courses repeat every 21 days in the absence of disease
    progression or unacceptable toxicity.

    ARM II: Patients receive cisplatin IV over 1 hour on day 1 and veliparib PO BID on days
    1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable
    toxicity.

    After completion of study treatment, patients are followed up every 9 weeks for 54 weeks,
    every 18 weeks until progression, and then every 6 months for up to 5 years after
    progression.

    Trial Arms

    Name Type Description Interventions
    Arm I (cisplatin and placebo) Active Comparator Patients receive cisplatin IV over 1 hour on day 1 and placebo PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cisplatin
    Arm II (cisplatin and veliparib) Experimental Patients receive cisplatin IV over 1 hour on day 1 and veliparib PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cisplatin, Veliparib

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have metastatic breast cancer (stage IV disease) and be human epidermal
    growth factor receptor 2 (HER2) non-over expressing per 2013 American Society of
    Clinical Oncology (ASCO)-College of American Pathologists (CAP) HER testing
    guidelines (0 or 1+ by immunohistochemistry [IHC]; and/or HER2 ratio < 2.0 and HER2
    copy number < 4 signals/cell by in-situ hybridization [ISH])

    - Patients must also meet at least one of the following criteria:

    - Triple negative: histologically confirmed primary and/or metastatic site that is
    estrogen receptor (ER)-negative (=< 1%), progesterone receptor (PR)-negative (=<
    1%), and HER2-negative

    - BRCA mutation: previously confirmed deleterious breast cancer 1, early onset
    (BRCA1) or breast cancer 2, early onset (BRCA2) germline mutation (documentation
    required)

    - Patients must have measurable or non-measurable disease; patients must have a
    chest/abdominal computed tomography (CT) scan (or positron emission tomography
    [PET]/CT of diagnostic quality, conventional or spiral) and bone scan prior to
    registration; if the patient is unable to undergo CT with IV contrast due to allergy
    or renal insufficiency, a non-contrast CT may be performed; all scans needed for
    assessment of measurable disease must be performed within 28 days prior to
    registration; non-measurable disease must be assessed within 42 days prior to
    registration; all disease must be assessed and documented on the Baseline Tumor
    Assessment Form

    - Patients must have adequate tissue available

    - Patients must have =< 1 prior cytotoxic regimens for metastatic disease

    - Patients must have completed any prior radiation therapy and hormonal therapy at
    least 14 days prior to registration

    - Patients must not have received prior cisplatin or poly (adenosine diphosphate
    [ADP]-ribose) polymerase (PARP) inhibitors; prior carboplatin in the
    adjuvant/neoadjuvant setting and prior treatment with iniparib is allowed, if
    completed more than 6 months prior to study entry

    - Patients must not have received any chemotherapy within 14 days prior to registration

    - Patients must not have received any immunotherapy, biologic or any investigational
    drug within 28 days prior to registration; patients must not have received
    bevacizumab within 42 days prior to registration

    - Patients may receive bisphosphonates or denosumab concurrently with study treatment
    provided it has been started at least 7 days prior to registration

    - Patients must have recovered to =< grade 2 following a significant adverse event or
    toxicity attributed to previous anti-cancer treatment

    - Patients must have a performance status of 0-2 by Zubrod criteria

    - Peripheral granulocyte count of >= 1,500/mL within 21 days prior to registration

    - Hemoglobin >= 9 g/dL within 21 days prior to registration

    - Platelet count >= 100,000/ mL within 21 days prior to registration

    - Bilirubin =< 1.5 mg/dL (or =< 3.0 mg/dL if due to Gilbert's syndrome or if liver
    metastases are present)

    - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x
    institutional upper limit of normal (IULN) (or =< 5 x IULN if liver metastases are
    present)

    - Patients must have adequate renal function with serum creatinine level =< IULN within
    21 days prior to registration

    - Patients must have serum chemistries (including potassium and magnesium) within 21
    days prior to registration to obtain baseline values

    - Patients must not have a clinically relevant hearing impairment >= grade 2

    - Patients must be able to swallow whole capsules

    - Patients with known brain metastases must have clinically controlled neurologic
    symptoms, defined as surgical excision and/or radiation therapy followed by 14 days
    of stable neurologic function prior to registration

    - Patients must not have any incidence of or uncontrolled medical illness (e.g. active
    cardiac symptoms, active systemic infection, etc.) that would limit the patient's
    ability to participate in the protocol

    - Patients must not have baseline peripheral neuropathy that exceeds grade 1

    - Patients must have a complete history and physical examination within 28 days prior
    to registration

    - Patients must not be pregnant or nursing; men and women of reproductive potential
    must have agreed to use an effective contraceptive method; a woman is considered to
    be of reproductive potential" if she has had menses at any time in the preceding 12
    consecutive months; in addition to routine contraceptive methods, "effective
    contraception" also includes heterosexual celibacy and surgery intended to prevent
    pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
    bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
    previously celibate patient chooses to become heterosexually active during the time
    period for use of contraceptive measures outlined in the protocol, he/she is
    responsible for beginning contraceptive measures

    - No other prior malignancy is allowed except for the following: adequately treated
    basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
    stage I or II cancer from which the patient is currently in complete remission, or
    any other cancer from which the patient has been disease free for five years

    - Patients must agree to have specimens submitted for germline deoxyribonucleic acid
    (DNA) sequencing and other correlative studies

    - Patients must be informed of the investigational nature of this study and must sign
    and give written informed consent in accordance with institutional and federal
    guidelines

    - As part of the Oncology Patient Enrollment Network (OPEN) registration process the
    treating institution's identity is provided in order to ensure that the current
    (within 365 days) date of institutional review board approval for this study had been
    entered in the system

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression-free survival, defined as radiologic progression of disease by Response Evaluation Criteria in Solid Tumors or unequivocal progression of non-measurable disease in the opinion of the treating physician

    Secondary Outcome Measures

    Clinical benefit rate

    Overall survival

    Response rate (measurable disease only)

    Trial Keywords