Evidence map›Paper›PMID 25589624›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2015

Randomized Trial of Oral Cyclophosphamide and Veliparib in High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers, or BRCA-Mutant Ovarian Cancer.

Shivaani Kummar, Amit M Oza, Gini F Fleming, Daniel M Sullivan, David R Gandara, Michael J Naughton, Miguel A Villalona-Calero, Robert J Morgan, Peter M Szabo, Ahrim Youn and 13 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01306032 (Phase II Randomized Trial of ABT-888 in Combination With Metronomic Oral Cyclophosphamide in Refractory BRCA-Positive Ovarian, Primary Peritoneal, Ovarian High-Grade Serous Carcinoma, Fallopian Tube Cancer, or Triple-Negative Breast Cancer), which is not on this map. Cited by 62 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 10 pooled it
–field-weighted citation impact
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.

NCT01306032 phase2completednot on this map

Phase II Randomized Trial of ABT-888 in Combination With Metronomic Oral Cyclophosphamide in Refractory BRCA-Positive Ovarian, Primary Peritoneal, Ovarian High-Grade Serous Carcinoma, Fallopian Tube Cancer, or Triple-Negative Breast Cancer

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2011 to 2016Enrolled124ConditionsOvarian Cancer, Primary Peritoneal Cancer, Serous Carcinoma Cancer, Triple-Negative Breast CancerArmsABT-888, Cyclophosphamide
3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 10 syntheses or guidelines pooled it.

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  11. Article
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  16. Recent Insights into PARP and Immuno-Checkpoint Inhibitors in Epithelial Ovarian Cancer.International journal of environmental research and public health · 2022
    Review
  17. Review
  18. Article
  19. Towards Personalized Management of Ovarian Cancer.Cancer management and research · 2022
    Review
  20. Review

2 more citing papers are in PubMed but not listed here.

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

23 authors.

Shivaani KummarNational Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Amit M OzaPrincess Margaret Hospital, University of Toronto, Ontario, Canada.
Gini F FlemingThe University of Chicago Medical Center, Chicago, Illinois.
Daniel M SullivanH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
David R GandaraUniversity of California Davis Cancer Center, Davis, California.
Michael J NaughtonWashington University School of Medicine, St. Louis, Missouri.
Miguel A Villalona-CaleroThe Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, Ohio.
Robert J MorganCity of Hope Comprehensive Cancer Center, Duarte, California.
Peter M SzaboNational Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Ahrim YounNational Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Alice P ChenNational Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Jiuping JiLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Deborah E AllenNational Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Chih-Jian LihLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Michele G MehaffeyLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
William D WalshLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Paul M McGregorLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Seth M SteinbergNational Cancer Institute, National Institutes of Health, Bethesda, Maryland.
P Mickey WilliamsLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Robert J KindersLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Barbara A ConleyNational Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Richard M SimonNational Cancer Institute, National Institutes of Health, Bethesda, Maryland.
James H DoroshowNational Cancer Institute, National Institutes of Health, Bethesda, Maryland. doroshoj@mail.nih.gov.

Funding

Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
Phase 01 Clinical TrialsZIABC011078 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DOROSHOW, JAMES · 2009 to 2025
$9.0M
Integrative Molecular Epidemiology WorkshopR25CA174664 · NCI · AMERICAN ASSOCIATION FOR CANCER RESEARCH · PI Shelley S Tworoger · 2013 to 2026
$2.8M
Phase 01 Clinical TrialsZ01BC011078 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DOROSHOW, JAMES · 2008 to 2008
$96k
CCR NIH HHS HHSN261200800001CIntramural NIH HHS Z01 BC011078NCATS NIH HHS UL1 TR000430NCI NIH HHS HHSN261200800001ENCI NIH HHS N01-CM-2011-00032NCI NIH HHS N01-CM-2011-00038NCI NIH HHS N01-CM-2011-00071NCI NIH HHS N01-CM-2011-00099NCI NIH HHS N01-CM-2011-00100NCI NIH HHS R25 CA174664
6 · The paper itself

Abstract

purposeVeliparib, a PARP inhibitor, demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase I trial. To define the relative contribution of PARP inhibition to the observed clinical activity, we conducted a randomized phase II trial to determine the response rate of veliparib in combination with cyclophosphamide compared with cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or in patients with pretreated primary peritoneal, fallopian tube, or high-grade serous ovarian cancers (HGSOC). EXPERIMENTAL

designAdult patients were randomized to receive cyclophosphamide alone (50 mg orally once daily) or with veliparib (60 mg orally once daily) in 21-day cycles. Crossover to the combination was allowed at disease progression.

resultsSeventy-five patients were enrolled and 72 were evaluable for response; 38 received cyclophosphamide alone and 37 the combination as their initial treatment regimen. Treatment was well tolerated. One complete response was observed in each arm, with three partial responses (PR) in the combination arm and six PRs in the cyclophosphamide alone arm. Genetic sequence and expression analyses were performed for 211 genes involved in DNA repair; none of the detected genetic alterations were significantly associated with treatment benefit.

conclusionThis is the first trial that evaluated single-agent, low-dose cyclophosphamide in HGSOC, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well tolerated and clinical activity was observed; the addition of veliparib at 60 mg daily did not improve either the response rate or the median progression-free survival.

Indexed as

Administration, OralAdultAgedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesCyclophosphamideCystadenocarcinoma, SerousDisease-Free SurvivalFallopian Tube NeoplasmsFemaleGenes, BRCA1Genes, BRCA2HumansMiddle AgedOvarian NeoplasmsAntineoplastic AgentsBenzimidazolesCyclophosphamideveliparib

Identifiers

PMID25589624
PMCPMC4383665

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Registered trials

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.