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Cisplatin With or Without Veliparib in Treating Patients With Stage IV Triple-Negative and/or BRCA Mutation-Associated Breast Cancer

This study is currently recruiting participants.
Verified November 2017 by National Cancer Institute (NCI)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02595905
First Posted: November 4, 2015
Last Update Posted: November 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
November 3, 2015
November 4, 2015
November 29, 2017
July 7, 2016
October 31, 2021   (Final data collection date for primary outcome measure)
PFS [ Time Frame: Time from registration (randomization) to progression or death due to any cause, assessed up to 5 years ]
3 separate analyses will be performed: comparing veliparib to no veliparib in the BRCA mutation-carriers, BRCA mutation-negative BRCAness-like group, and BRCA mutation-negative non-BRCA-like group. A stratified log-rank test will be used to compare PFS between the two arms in an intention to treat (ITT) analysis where stratification is by line of therapy. For the brain metastases cohort, a stratified log-rank test will be used to compare PFS between the two arms in an ITT analysis where stratification is by modified breast-graded prognostic assessment (GPA) and prior systemic therapies.
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 [ Time Frame: Time from registration (randomization) to progression or death due to any cause, assessed up to 5 years ]
3 separate analyses will be performed: comparing veliparib to no veliparib in the BRCA mutation-carriers, BRCA mutation-negative BRCAness-like group, and BRCA mutation-negative non-BRCA-like group. A stratified log-rank test will be used to compare PFS between the two arms in an intention to treat analysis where stratification is line by line.
Complete list of historical versions of study NCT02595905 on ClinicalTrials.gov Archive Site
  • Clinical benefit rate [ Time Frame: Up to 5 years ]
    Clinical benefit will be assessed in all patients and will include those with complete or partial response and those with stable disease for 6 months. The primary analyses will be conducted using these binary responses using Fisher's exact test and logistic regression.
  • Overall survival [ Time Frame: Time from registration to death due to any cause, assessed up to a minimum of 5 years ]
    4 separate analyses will be performed: comparing veliparib to no veliparib in the BRCA mutation-carriers, BRCA mutation-negative BRCAness-like group, and BRCA mutation-negative non-BRCA-like group. A stratified log-rank test will be used to compare PFS between the two arms in an ITT analysis where stratification is line by line. For the brain metastases cohort, a stratified log-rank test will be used to compare OS between the two arms in an ITT analysis where stratification is by modified breast-GPA and prior systemic therapies.
  • Response rate (measurable disease only) [ Time Frame: Up to 5 years ]
    Patients who achieve complete or partial response will be classified as having a response. The primary analyses will be conducted using these binary responses using Fisher's exact test and logistic regression.
  • Clinical benefit rate [ Time Frame: Up to 5 years ]
    Clinical benefit will be assessed in all patients and will include those with complete or partial response and those with stable disease for 6 months. The primary analyses will be conducted using these binary responses using Fisher's exact test and logistic regression.
  • Overall survival [ Time Frame: Time from registration to death due to any cause, assessed up to a minimum of 5 years ]
    3 separate analyses will be performed: comparing veliparib to no veliparib in the BRCA mutation-carriers, BRCA mutation-negative BRCAness-like group, and BRCA mutation-negative non-BRCA-like group. A stratified log-rank test will be used to compare PFS between the two arms in an intention to treat analysis where stratification is line by line.
  • Response rate (measurable disease only) [ Time Frame: Up to 5 years ]
    Patients who achieve complete or partial response will be classified as having a response. The primary analyses will be conducted using these binary responses using Fisher's exact test and logistic regression.
Not Provided
Not Provided
 
Cisplatin With or Without Veliparib in Treating Patients With Stage IV Triple-Negative and/or BRCA Mutation-Associated Breast Cancer
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
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.

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.

II. To compare the efficacy of cisplatin with or without ABT-888 on PFS in patients with triple negative and/or gBRCA mutation-associated breast cancer and brain metastases. (Brain metastases cohort)

SECONDARY OBJECTIVES:

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

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

III. For patients in the brain metastases cohort, to compare the efficacy of cisplatin with or without ABT-888 on OS.

IV. For patients in the brain metastases cohort, to compare the efficacy of cisplatin with or without ABT-888 on intracranial and extracranial response rates (intracranial by Response Assessment Neuro-Oncology Criteria [RANO] and extracranial by Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]).

V. To compare toxicities of ABT-888 to placebo in each of the four 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 combined impact of PAM50 basal subtype and BRCAness phenotype on RR and PFS in patients treated with chemotherapy versus chemotherapy plus ABT-888.

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

V. Application of somatic BRCAness phenotype markers on metastatic tumor tissue to identify patients likely to benefit from platinum-based therapy and 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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • BRCA1 Mutation Carrier
  • BRCA2 Mutation Carrier
  • Breast Carcinoma Metastatic in the Brain
  • Estrogen Receptor Negative
  • HER2/Neu Negative
  • Progesterone Receptor Negative
  • Stage IV Breast Cancer AJCC v6 and v7
  • Triple-Negative Breast Carcinoma
  • Drug: Cisplatin
    Given IV
    Other Names:
    • 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
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Placebo
    Given PO
    Other Names:
    • placebo therapy
    • PLCB
    • sham therapy
  • Drug: Veliparib
    Given PO
    Other Names:
    • ABT-888
    • PARP-1 inhibitor ABT-888
  • Active Comparator: Arm I (cisplatin and placebo)
    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.
    Interventions:
    • Drug: Cisplatin
    • Other: Laboratory Biomarker Analysis
    • Other: Placebo
  • Experimental: Arm II (cisplatin and veliparib)
    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.
    Interventions:
    • Drug: Cisplatin
    • Other: Laboratory Biomarker Analysis
    • Drug: Veliparib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
235
Not Provided
October 31, 2021   (Final data collection date for primary outcome measure)

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 or suspected deleterious BRCA1 or BRCA2 germline mutation if the classification being used is the 5-tier classification; documentation of germline test results are 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, must agree to have specimens submitted for germline deoxyribonucleic acid (DNA) sequencing and other correlative studies
  • Patients must have had =< 1 prior cytotoxic regimen 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 except neurotoxicity which must be =< grade 1
  • Patients must have a performance status of 0-2 by Zubrod criteria
  • Absolute neutrophil count (ANC) 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 a history of uncontrolled seizure disorder; including focal or generalized seizure may not have had a seizure within one year prior to registration
  • Patients with known brain metastases must either meet the additional criteria and enroll as part of the brain metastases cohort, or else 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 with previously treated progressive brain metastases are not eligible for the standard cohort, but may be considered for the brain metastases cohort
  • 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 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
  • BRAIN METASTASES COHORT

    • In addition to all of the previous eligibility criteria, patients with progressive brain metastases who do not satisfy the conditions to enroll in the standard cohort (neurologic stability for 14 days following surgery and/or radiation therapy) must also meet the following criteria to enroll as part of the brain metastases cohort:

      • Patients with progressive brain metastases must have a baseline brain magnetic resonance imaging (MRI) within 28 days prior to registration; brain metastases must be progressive and >= 10 mm in longest dimension on radiographic imaging AFTER prior intracranial radiation (IR) therapy (i.e., whol brain radiation therapy [WBRT], stereotactic radiosurgery [SRS], gamma knife [GK] or local equivalent); patients must not have evidence of diffuse leptomeningeal disease on brain MRI or by previously documented cerebrospinal fluid (CSF) cytology; discrete dural metastases are permitted; there must be no evidence of hemorrhage or impending herniation on baseline brain imaging; patients with contraindication to gadolinium-enhanced MRI imaging are not eligible
      • Patients must be on a stable or decreasing dose of steroids for >= 7 days prior to registration
      • If patient had an open brain biopsy, at least 28 days must have elapsed between biopsy and registration
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Puerto Rico,   United States
 
 
NCT02595905
NCI-2015-01912
NCI-2015-01912 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1416
S1416 ( Other Identifier: SWOG )
S1416 ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Eve Rodler Southwest Oncology Group
National Cancer Institute (NCI)
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP