Evidence map›Paper›PMID 34620496›Full record

Trial reportGynecologic oncology2021

Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer.

Payal D Shah, Stephanie L Wethington, Cheyenne Pagan, Nawar Latif, Janos Tanyi, Lainie P Martin, Mark Morgan, Robert A Burger, Ashley Haggerty, Haley Zarrin and 12 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Gynecologic oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03462342 (Combination ATR and PARP Inhibitor), which is not on this map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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.

NCT03462342 phase2completednot on this map

Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD 6738 and Olaparib in Recurrent Ovarian Cancer

TypeinterventionalSponsorUniversity of PennsylvaniaRan2018 to 2025Enrolled123ConditionsHigh Grade Serous CarcinomaArmsOlaparib Pill, AZD6738
3 · Its place in the literature

Who cites it

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.

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34 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

22 authors at 4 institutions in 2 countries.

Payal D ShahBasser Center for BRCA, Perelman School of Medicine at the University of Pennsylvania, United States of America; Division of Medical Oncology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Stephanie L WethingtonThe Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medicine, United States of America.
Cheyenne PaganDivision of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Nawar LatifDivision of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Janos TanyiDivision of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Lainie P MartinDivision of Medical Oncology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Mark MorganDivision of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Robert A BurgerDivision of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Ashley HaggertyDivision of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Haley ZarrinDivision of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Diego RodriguezDivision of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Susan DomchekBasser Center for BRCA, Perelman School of Medicine at the University of Pennsylvania, United States of America; Division of Medical Oncology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Ronny DrapkinBasser Center for BRCA, Perelman School of Medicine at the University of Pennsylvania, United States of America; Division of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Ie-Ming ShihThe Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medicine, United States of America.
Simon A SmithAstraZeneca, R&D Oncology, Cambridge, UK.
Emma DeanAstraZeneca, R&D Oncology, Cambridge, UK.
Stéphanie GaillardThe Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medicine, United States of America.
Deborah ArmstrongThe Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medicine, United States of America.
Drew A TorigianDepartment of Radiology, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Wei-Ting HwangDivision of Biostatistics, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Robert GiuntoliDivision of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America.
Fiona SimpkinsDivision of Gynecology Oncology, Department of Obstetrics & Gynecology, Perelman School of Medicine at the University of Pennsylvania, United States of America. Electronic address: Fiona.Simpkins@pennmedicine.upenn.edu.
University of Pennsylvania · USJohns Hopkins University · USAstraZeneca (United Kingdom) · GBJohns Hopkins Medicine · US

Funding

SPORE in Ovarian CancerP50CA228991 · NCI · JOHNS HOPKINS UNIVERSITY · PI Ronny I DRAPKIN, IE-MING SHIH · 2018 to 2026
$20.5M
A novel more effective genotoxic therapy for ovarian cancerR37CA215436 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SIMPKINS, FIONA · 2018 to 2024
$2.6M
NCI NIH HHS P50 CA228991NCI NIH HHS R37 CA215436
6 · The paper itself

Abstract

objectivePlatinum-resistant, high-grade serous ovarian cancer (HGSOC) has limited treatment options. Preclinical data suggest that poly(ADP-ribose) polymerase inhibitors (PARPi) and ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) are synergistic. CAPRI (NCT03462342) is an investigator-initiated study of olaparib plus ceralasertib in recurrent HGSOC. Herein, we present results from the platinum-resistant cohort.

methodsA Simon 2-stage design was utilized. Platinum-resistant HGSOC patients received ceralasertib 160 mg orally daily, days 1-7 and olaparib 300 mg orally twice daily, days 1-28 of a 28-day cycle until toxicity or progression. Primary endpoints were toxicity and efficacy including objective response rate (ORR) by RECIST. Secondary endpoint was progression-free survival (PFS). The null hypothesis (≤5% ORR) would be rejected if there were ≥ 1 responses in 12 patients.

resultsFourteen PARPi-naïve patients were evaluable for toxicity; 12 were evaluable for response. Three had BRCA1 mutations (1 germline, 2 somatic). Adverse events possibly related to treatment were primarily grade (G) 1/2. G3 toxicities included nausea (14.3%), fatigue (7.1%), anorexia (7.1%), and anemia (7.1%). No objective responses occurred. Best response was stable disease in 9 patients and progressive disease in three. Five patients had a ≥ 20% to <30% reduction in disease burden, including 3 with BRCA1 mutations. Three of 11 patients (27%; 2 with BRCA1 mutations) evaluable by Gynecologic Cancer Intergroup criteria had >50% CA-125 decline, including 2 with CA-125 normalization. Median PFS was 4.2 months overall (90% CI:3.5-8.2) and 8.2 months (3.6 months-not determined) for patients with BRCA1 mutations.

conclusionsOlaparib plus ceralasertib is well-tolerated. No objective responses occurred, though a signal of activity was seen particularly in disease associated with BRCA1. Further evaluation of this combination should include alternate dosing strategies in genomically-selected populations.

Indexed as

Administration, OralAgedAntineoplastic Combined Chemotherapy ProtocolsAtaxia Telangiectasia Mutated ProteinsBRCA1 ProteinDrug Administration ScheduleDrug Resistance, NeoplasmFemaleHumansIndolesMagnetic Resonance ImagingMiddle AgedMorpholinesNeoplasm Recurrence, LocalOvarian NeoplasmsOvaryAtaxia Telangiectasia Mutated ProteinsATR protein, humanBRCA1 ProteinBRCA1 protein, humanceralasertibIndolesMorpholinesolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsProtein Kinase InhibitorsPyrimidinesSulfonamidesATRCeralasertibOlaparibOvarian cancerPARPPlatinum-resistant

Identifiers

PMID34620496
PMCPMC9614917
OpenAlexW3203516197

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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.