Evidence map›Paper›PMID 33474828›Full record

ArticleCancer medicine2021

Phase 1 trial of olaratumab monotherapy and in combination with chemotherapy in pediatric patients with relapsed/refractory solid and central nervous system tumors.

Leo Mascarenhas, Chitose Ogawa, Theodore W Laetsch, Brenda J Weigel, Michael W Bishop, Julie Krystal, Scott C Borinstein, Emily K Slotkin, Jodi A Muscal, Pooja Hingorani and 5 more

Open access · goldAbstract readClinical Trial, Phase IMulticenter Study
In one paragraph

Article in Cancer medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Review
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

15 authors at 13 institutions in 2 countries.

Leo MascarenhasCancer and Blood Disease Institute, Children's Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0001-7790-0777
Chitose OgawaDepartment of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.
Theodore W LaetschDepartment of Pediatrics, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-8497-3138
Brenda J WeigelPediatric Hematology/Oncology, University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA.ORCID 0000-0003-1080-1402
Michael W BishopDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Julie KrystalDepartment of Pediatric Hematology/Oncology, Cohen Children's Medical Center, New Hyde Park, NY, USA.ORCID 0000-0002-7997-1015
Scott C BorinsteinDivision of Pediatric Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-1721-1520
Emily K SlotkinMemorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-4463-5759
Jodi A MuscalTexas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-3906-8534
Pooja HingoraniThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-4772-7456
Donna E LevyBiostatistics and Biometrics Division, Syneos Health, Morrisville, NC, USA.
Gary MoPK/PD and Pharmacometrics Division, Eli Lilly and Company, Indianapolis, IN, USA.ORCID 0000-0001-7805-5077
Ashwin ShahirOncology Division, Eli Lilly and Company, Indianapolis, IN, USA.
Jennifer WrightOncology Division, Eli Lilly and Company, Indianapolis, IN, USA.
Steven G DuBoisDana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0882-738X
Eli Lilly (United States) · USBaylor College of Medicine · USCenter for Cancer and Blood Disorders · USCohen Children's Medical Center · USHarvard University · USMemorial Sloan Kettering Cancer Center · USSt. Jude Children's Research Hospital · USSyneos Health (United States) · USThe University of Texas MD Anderson Cancer Center · USTokyo National Hospital · JPUniversity of Minnesota · USUniversity of Southern California · USVanderbilt University Medical Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Olaratumab is a monoclonal antibody that specifically binds to platelet-derived growth factor receptor alpha (PDGFRα) and blocks receptor activation. We conducted a phase 1 trial to evaluate the safety of olaratumab and determine a recommended dose in combination with three different chemotherapy regimens in children. Patients <18 years with relapsed/refractory solid or central nervous system tumors were enrolled to two dose levels of olaratumab. Patients received olaratumab monotherapy at 15 mg/kg (Part A) or 20 mg/kg (Part B) on Days 1 and 8 of the first 21-day cycle, followed by olaratumab combined with standard fixed doses of chemotherapy with doxorubicin, vincristine/irinotecan, or high-dose ifosfamide by investigator choice for subsequent 21-day cycles. In Part C, patients received olaratumab 20 mg/kg plus assigned chemotherapy for all cycles. Parts A-C enrolled 68 patients across three chemotherapy treatment arms; olaratumab in combination with doxorubicin (N = 16), vincristine/irinotecan (N = 26), or ifosfamide (N = 26). Three dose-limiting toxicities (DLTs) occurred during olaratumab monotherapy (at 15 mg/kg, grade [G] 4 alanine aminotransferase [ALT]; at 20 mg/kg, G3 lung infection and G3 gamma-glutamyl transferase). One DLT occurred during vincristine/irinotecan with olaratumab 20 mg/kg therapy (G3 ALT). Treatment-emergent adverse events ≥G3 in >25% of patients included neutropenia, anemia, leukopenia, lymphopenia, and thrombocytopenia. Pharmacokinetic profiles of olaratumab with chemotherapy were within the projected range based on adult data. There was one complete response (rhabdomyosarcoma [Part B vincristine/irinotecan arm]) and three partial responses (two rhabdomyosarcoma [Part A doxorubicin arm and Part C doxorubicin arm]; one pineoblastoma [Part B vincristine/irinotecan arm]). Olaratumab was tolerable and safely administered in combination with chemotherapy regimens commonly used in children and adolescents.

Indexed as

Drug Resistance, NeoplasmSalvage TherapyAdolescentAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsCentral Nervous System NeoplasmsChildChild, PreschoolDoxorubicinFemaleFollow-Up StudiesHumansIfosfamideIrinotecanMaleMaximum Tolerated DoseAntibodies, MonoclonalDoxorubicinIfosfamideIrinotecanolaratumabVincristinechemotherapyolaratumabpediatric cancerplatelet-derived growth factor receptor

Identifiers

PMID33474828
PMCPMC7897905
OpenAlexW3122478920

What Socratic holds

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LicenceCC BY
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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 Socratic graph.