Evidence map›Paper›PMID 26996385›Full record

Trial reportInvestigational new drugs2016

Randomized phase II trial of cyclophosphamide and the oral poly (ADP-ribose) polymerase inhibitor veliparib in patients with recurrent, advanced triple-negative breast cancer.

Shivaani Kummar, James L Wade, Amit M Oza, Daniel Sullivan, Alice P Chen, David R Gandara, Jiuping Ji, Robert J Kinders, Lihua Wang, Deborah Allen and 3 more

Abstract readClinical Trial, Phase IIComparative StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Investigational new drugs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 8 pooled it
3.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 8 syntheses or guidelines pooled it, 74 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 8 institutions in 2 countries.

Shivaani KummarNational Cancer Institute, National Institutes of Health, 31 Center Drive, Room 3A44, Bethesda, MD, 20814, USA.
James L WadeThe University of Chicago Medical Center, Chicago, IL, USA.
Amit M OzaPrincess Margaret Hospital, University of Toronto, Toronto, ON, Canada.
Daniel SullivanH. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Alice P ChenNational Cancer Institute, National Institutes of Health, 31 Center Drive, Room 3A44, Bethesda, MD, 20814, USA.
David R GandaraUniversity of California Davis Cancer Center, Davis, CA, USA.
Jiuping JiLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Robert J KindersLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Lihua WangLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Deborah AllenNational Cancer Institute, National Institutes of Health, 31 Center Drive, Room 3A44, Bethesda, MD, 20814, USA.
Geraldine O'Sullivan CoyneNational Cancer Institute, National Institutes of Health, 31 Center Drive, Room 3A44, Bethesda, MD, 20814, USA.
Seth M SteinbergNational Cancer Institute, National Institutes of Health, 31 Center Drive, Room 3A44, Bethesda, MD, 20814, USA.
James H DoroshowNational Cancer Institute, National Institutes of Health, 31 Center Drive, Room 3A44, Bethesda, MD, 20814, USA. doroshoj@mail.nih.gov.
National Cancer Institute · USNational Institutes of Health · USFrederick National Laboratory for Cancer Research · USLeidos (United States) · USMoffitt Cancer Center · USUniversity of California, Davis · USUniversity of Chicago Medical Center · USUniversity of Toronto · CA

Funding

Phase 01 Clinical TrialsZIABC011078 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DOROSHOW, JAMES · 2009 to 2025
$9.0M
Phase 01 Clinical TrialsZ01BC011078 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DOROSHOW, JAMES · 2008 to 2008
$96k
CCR NIH HHS HHSN261200800001CIntramural NIH HHS Z01 BC011078NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

Background In tumors carrying BRCA mutations, DNA damage caused by standard cytotoxic chemotherapy can be potentiated by poly [ADP-ribose] polymerase (PARP) inhibitors, leading to increased cell death through synthetic lethality. Individuals carrying mutations in BRCA have an increased incidence of triple negative breast cancer (TNBC). In order to assess the role of PARP inhibition in the treatment of TNBC, we conducted a randomized phase II trial of the combination of veliparib, a small molecule PARP inhibitor, with the cytotoxic agent cyclophosphamide versus cyclophosphamide alone in patients with refractory TNBC. Methods Adult patients with TNBC were randomized to receive oral cyclophosphamide 50 mg once daily with or without oral veliparib at 60 mg daily in 21-day cycles. Patients on the cyclophosphamide arm could crossover to the combination arm at disease progression. Results Forty-five patients were enrolled; 18 received cyclophosphamide alone and 21 received the combination as their initial treatment regimen. Lymphopenia was the most common grade 3/4 toxicity noted in both arms. One patient in the cyclophosphamide alone arm, and 2 in the combination arm had objective responses. Response rates and median progression free survival did not significantly differ between both treatment arms. Conclusion The addition of veliparib to cyclophosphamide, at the dose and schedule evaluated, did not improve the response rate over cyclophosphamide treatment alone in patients with heavily pre-treated triple-negative breast cancer.

Indexed as

Administration, OralAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesCross-Over StudiesCyclophosphamideDisease-Free SurvivalFemaleHumansMiddle AgedNeoplasm Recurrence, LocalPoly(ADP-ribose) Polymerase InhibitorsTreatment OutcomeTriple Negative Breast NeoplasmsBenzimidazolesCyclophosphamidePoly(ADP-ribose) Polymerase InhibitorsveliparibBRCADNA damage repairHR defectMetronomic cyclophosphamidePARP inhibition

Identifiers

PMID26996385
PMCPMC4860030
OpenAlexW2309983655

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.