Evidence map›Paper›PMID 28194539›Full record

ArticleInvestigational new drugs2017

Phase I trial of MEK 1/2 inhibitor pimasertib combined with mTOR inhibitor temsirolimus in patients with advanced solid tumors.

Monica Mita, Siqing Fu, Sarina Anne Piha-Paul, Filip Janku, Alain Mita, Ronald Natale, Wei Guo, Charles Zhao, Razelle Kurzrock, Aung Naing

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

Article in Investigational new drugs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01378377 (Phase I Dose Escalation Trial of MEK1/2 Inhibitor MSC1936369B Combined With Temsirolimus in Subjects With Advanced Solid Tumors), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–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.

NCT01378377 phase1terminatednot on this map

Phase I Dose Escalation Trial of MEK1/2 Inhibitor MSC1936369B Combined With Temsirolimus in Subjects With Advanced Solid Tumors

TypeinterventionalSponsorEMD SeronoRan2011 to 2012Enrolled33ConditionsAdvanced Solid TumorArmsPimasertib, Temsirolimus
3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. TargetingInternational journal of molecular sciences · 2020
    Review
  7. Article
  8. Review
  9. Review
  10. New Horizons inFrontiers in oncology · 2019
    Review
  11. Article
  12. Pharmacology of Pimasertib, A Selective MEK1/2 Inhibitor.European journal of drug metabolism and pharmacokinetics · 2018
    Review
  13. Article
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

10 authors.

Monica MitaSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Siqing FuDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Sarina Anne Piha-PaulDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Filip JankuDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Alain MitaSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Ronald NataleSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Wei GuoGlobal Biostatistics, EMD Serono Inc., Billerica, MA, 01821, USA.
Charles ZhaoClinical Oncology Early Development, EMD Serono Inc., Billerica, MA, 01821, USA.
Razelle KurzrockDivision of Hematology and Oncology, University of California San Diego (UCSD) School of Medicine and UCSD Moores Cancer Center, La Jolla, CA, 92093, USA.
Aung NaingDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. anaing@mdanderson.org.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Kathrin Milbury · 1985 to 2026
$290.8M
Center for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4M
NCATS NIH HHS UL1 TR000371NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

Background Dual inhibition of activated MAPK and mTOR signaling pathways may enhance the antitumor efficacy of the MEK 1/2 inhibitor pimasertib and the mTOR inhibitor temsirolimus given in combination. Methods In this phase I study, patients with refractory advanced solid tumors (NCT01378377) received once-weekly temsirolimus plus once-daily oral pimasertib in 21-day cycles in a modified 3 + 3 dose-escalation design. The maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of pimasertib in combination with temsirolimus, safety and pharmacokinetics (PK) were investigated. Results Of 33 patients evaluated, all experienced ≥1 treatment-emergent adverse event (TEAE) and 31 had treatment-related TEAEs, most frequently stomatitis and thrombocytopenia. TEAEs were reversible. No deaths were attributed to treatment. Nine patients had dose-limiting toxicities (stomatitis, thrombocytopenia, serum creatinine phosphokinase increase, visual impairment) and the MTD was determined as 45 mg/day pimasertib plus 25 mg/week temsirolimus. However, due to overlapping toxicities no further investigations were performed and the RP2D was not defined. PK profiles of both agents were not adversely affected. Seventeen patients (17/26 patients) had a best response of stable disease; five had stable disease lasting >12 weeks. Conclusions The RP2D was not defined and the pimasertib plus temsirolimus combination investigated did not warrant further study.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsFemaleHumansMaleMAP Kinase Kinase Kinase 1MAP Kinase Kinase Kinase 2Maximum Tolerated DoseMiddle AgedNeoplasmsNiacinamideProtein Kinase InhibitorsSirolimusTOR Serine-Threonine KinasesMAP Kinase Kinase Kinase 1MAP Kinase Kinase Kinase 2MTOR protein, humanN-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamideNiacinamideProtein Kinase InhibitorsSirolimustemsirolimusTOR Serine-Threonine KinasesMAPKMEKPimasertibSafetySolid tumorsTemsirolimus

Identifiers

PMID28194539
PMCPMC5935457

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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.