Evidence map›Paper›PMID 38135713›Full record

Trial reportBritish journal of cancer2024

NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma.

Michael Cecchini, James M Cleary, Yu Shyr, Joseph Chao, Nataliya Uboha, May Cho, Anthony Shields, Shubham Pant, Laura Goff, Kristen Spencer and 13 more

Open access · hybridAbstract readClinical Trial, Phase IIClinical Trial, Phase I
In one paragraph

Trial report in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.8field-weighted citation impact, top 12% 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

9 citing papers in PubMed, 8 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

23 authors at 11 institutions in 1 country.

Michael CecchiniDepartment of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, 06510, USA. Michael.cecchini@yale.edu.ORCID 0000-0003-3504-0128
James M ClearyDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Yu ShyrDepartment of Biostatistics, Vanderbilt University, Nashville, TN, 37203, USA.
Joseph ChaoDepartment of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA, 91010, USA.
Nataliya UbohaDepartment of Medicine, University of Wisconsin, Madison, WI, 53792, USA.
May ChoDepartment of Medicine, University of California Irvine, Irvine, CA, 92868, USA.
Anthony ShieldsKarmanos Cancer Institute, Wayne State University, Detroit, MI, 48201, USA.
Shubham PantDepartment of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, 77030, USA.
Laura GoffDepartment of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, 37203, USA.
Kristen SpencerDepartment of Medicine, Perlmutter Cancer Center of NYU Langone Health and NYU Grossman School of Medicine, New York, NY, 10016, USA.
Edward KimDepartment of Internal Medicine, University of California Davis, Davis, CA, 95817, USA.ORCID 0000-0002-8660-7465
Stacey SteinDepartment of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, 06510, USA.
Jeremy S KortmanskyDepartment of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, 06510, USA.
Sandra CanosaDepartment of Pathology, Yale University School of Medicine, New Haven, CT, 06510, USA.
Jeffrey SklarDepartment of Pathology, Yale University School of Medicine, New Haven, CT, 06510, USA.
Elizabeth M SwisherDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, 98195, USA.
Marc RadkeDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, 98195, USA.
Percy IvyCancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, 20892, USA.
Scott BoernerDepartment of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, 06510, USA.
Diane E DureckiDepartment of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, 06510, USA.
Chih-Yuan HsuDepartment of Biostatistics, Vanderbilt University, Nashville, TN, 37203, USA.
Patricia LoRussoDepartment of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, 06510, USA.
Jill LacyDepartment of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, 06510, USA.
Yale University · USVanderbilt University · USUniversity of Washington · USCity of Hope · USDana-Farber Cancer Institute · USNational Cancer Institute · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, Davis · USUniversity of California, Irvine · USUniversity of Wisconsin–Madison · USWayne State University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9M
XPO1 inhibitors Selinexor and Eltanexor in Combination with Venetoclax and Decitabine (ASTX727) in AMLUM1CA186709 · NCI · DANA-FARBER CANCER INST · PI KEITH T FLAHERTY, DONALD W. KUFE · 2014 to 2026
$25.9M
ViKTriY-PC Consortium Phase II SupplementUM1CA186689 · NCI · YALE UNIVERSITY · PI Patricia M. LoRusso · 2014 to 2026
$22.2M
Phase I Molecular and Clinical Pharmacodynamic Trials ETCTNUM1CA186717 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI A. Dimitrios Colevas, Alexey V. Danilov · 2014 to 2026
$19.8M
Immunomodulatory Effects of Targeting DNA Repair with Novel Temozolomide Combinations in Colorectal CancerK08CA255465 · NCI · YALE UNIVERSITY · PI CECCHINI, MICHAEL · 2021 to 2025
$1.3M
NCATS NIH HHS UL1 TR001863NCI NIH HHS K08 CA255465NCI NIH HHS P30 CA093373NCI NIH HHS UM1 CA186689NCI NIH HHS UM1 CA186709NCI NIH HHS UM1 CA186717
6 · The paper itself

Abstract

backgroundOur preclinical work revealed tumour hypoxia induces homologous recombination deficiency (HRD), increasing sensitivity to Poly (ADP-ribose) polymerase inhibitors. We aimed to induce tumour hypoxia with ramucirumab thereby sensitising tumours to olaparib. PATIENTS AND

methodsThis multi-institution single-arm Phase 1/2 trial enrolled patients with metastatic gastroesophageal adenocarcinoma refractory to ≥1 systemic treatment. In dose escalation, olaparib was evaluated at escalating dose levels with ramucirumab 8 mg/kg day 1 in 14-day cycles. The primary endpoint of Phase 1 was the recommended Phase 2 dose (RP2D), and in Phase 2 the primary endpoint was the overall response rate (ORR).

resultsFifty-one patients received ramucirumab and olaparib. The RP2D was olaparib 300 mg twice daily with ramucirumab 8 mg/kg. In evaluable patients at the RP2D the ORR was 6/43 (14%) (95% CI 4.7-25.6). The median progression-free survival (PFS) was 2.8 months (95% CI 2.3-4.2) and median overall survival (OS) was 7.3 months (95% CI 5.7-13.0). Non-statistically significant improvements in PFS and OS were observed for patients with tumours with mutations in HRD genes.

conclusionsOlaparib and ramucirumab is well-tolerated with efficacy that exceeds historical controls with ramucirumab single agent for gastric cancer in a heavily pre-treated patient population.

Indexed as

AdenocarcinomaEsophageal NeoplasmsPiperazinesStomach NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsEsophagogastric JunctionHumansPhthalazinesRamucirumabolaparibPhthalazinesPiperazinesRamucirumab

Identifiers

PMID38135713
PMCPMC10844282
OpenAlexW4390103317

What OpenQuestion holds

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Registered trials

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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.