NCT02595905|CompletedPhase 2Results

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

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, With or Without Brain Metastases

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2015-01912S1416U10CA180888

Study Type

interventional

Target

344

Locations

2 countries

Sites

810

Timeline

RegisteredNov 2015

StartedSep 2016

CompletionMar 2025

Brief Summary

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 (recurrent) or has or has not spread to the brain (brain metastases). 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. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as veliparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

344

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Sep 2016

Longer than P75 for phase_2

Geographic Reach

2 countries

810 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

8.5 years study duration

First Submitted

Initial submission to the registry

November 3, 2015

Completed

1 day until next milestone

First Posted

Study publicly available on registry

November 4, 2015

Completed

11 months until next milestone

Study Start

First participant enrolled

September 15, 2016

Completed

8.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2025

Completed

3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 21, 2025

Completed

1 year until next milestone

Results Posted

Study results publicly available

April 8, 2026

Completed

Last Updated

April 8, 2026

Status Verified

February 1, 2026

Enrollment Period

8.3 years

First QC Date

November 3, 2015

Results QC Date

December 29, 2025

Last Update Submit

March 23, 2026

Conditions

Metastatic BRCA Hereditary Breast Carcinoma Metastatic Breast Carcinoma Metastatic Malignant Neoplasm in the Brain Metastatic Triple-Negative Breast Carcinoma Recurrent Breast Carcinoma Stage IV Breast Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

Progression-free Survival (PFS)
Veliparib will be compared 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. 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 is defined as radiologic progression of disease by RECIST criteria or unequivocal progression of nonmeasurable disease in the opinion of the treating physician. Progression in the brain metastases cohort is defined as the first detection of radiologic progression of intracranial, extracranial or both intracranial and extracranial disease.
Time from registration (randomization) to progression or death due to any cause, assessed up to 5 years

Secondary Outcomes (3)

Overall Survival (OS)
Time from registration to death due to any cause, assessed up to a minimum of 5 years
Response Rate (Measurable Disease Only)
Up to 5 years
Clinical Benefit Rate
Up to 5 years

Study Arms (2)

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. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: CisplatinOther: Laboratory Biomarker AnalysisOther: Placebo Administration

Arm II (cisplatin and veliparib)

EXPERIMENTAL

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

Drug: CisplatinOther: Laboratory Biomarker AnalysisDrug: Veliparib

Interventions

CisplatinDRUG

Given IV

Also known as: 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)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (cisplatin and placebo)Arm II (cisplatin and veliparib)

Placebo AdministrationOTHER

Given PO

Arm I (cisplatin and placebo)

VeliparibDRUG

Given PO

Also known as: ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

Arm II (cisplatin and veliparib)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Patients must have metastatic and/or recurrent (distant or locoregionally recurrent) breast cancer and be 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 \[ISH\])
Local Regional Recurrence
In the breast (after preserving therapy)
In the chest wall (after mastectomy)
In the ipsilateral/parasternal/infra-or supraclavicular lymph nodes
In the skin of the chest wall (not breast)
In the reconstructed breast
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/pelvis computed tomography (CT) scan (or positron emission tomography \[PET\]/CT of diagnostic quality, conventional or spiral) 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 be women or men ≥ 18 years of age
Patients must have adequate tissue available and must agree to have specimens submitted for germline BRCA deoxyribonucleic acid (DNA) sequencing and other correlative studies
NOTE: Blood for BRCA mutation testing is to be collected and submitted after registration but before treatment
Patients must have had =\< 1 prior cytotoxic regimen for metastatic disease (unless enrolling in the Progressive Brain Metastases Cohort); note that endocrine and immunotherapies do not count as cytotoxic regimens
+26 more criteria

You may not qualify if:

Patients must not have received prior cisplatin or poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitors; prior carboplatin in the adjuvant/neoadjuvant setting is allowed, if completed more than 12 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 must not have a clinically relevant hearing impairment \>= grade 2
Patients must not have treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS) or features suggestive of AML/MDS
Patients must not have had prior allogeneic bone marrow transplant or double umbilical cord blood transplantation
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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (810)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC