Evidence map›Paper›PMID 25290091›Full record

Trial reportBritish journal of cancer2014

A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours.

I Brana, R Berger, T Golan, P Haluska, J Edenfield, J Fiorica, J Stephenson, L P Martin, S Westin, P Hanjani and 9 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01243762 (Phase I Parallel Arm Study of MK-0646), which is not on this map. Cited by 47 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 2 pooled it
8.2field-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.

NCT01243762 phase1terminatednot on this map

Phase I Parallel Arm Study of MK-0646 (Dalotuzumab) + MK-2206, Dalotuzumab + MK-0752, and Dalotuzumab + MK-8669 (Ridaforolimus) Doublets (MK-MK Doublets) in Patients With Advanced Cancer

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2010 to 2013Enrolled47ConditionsNeoplasms MalignantArmsdalotuzumab, MK-0752, ridaforolimus, MK-2206
3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Predictors of survival in alveolar rhabdomyosarcoma in the US.Annals of medicine and surgery (2012) · 2026
    Article
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  13. Emerging role of MYB transcription factors in cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2024
    Review
  14. Review
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  16. IGF-1R targeting in cancer - does sub-cellular localization matter?Journal of experimental & clinical cancer research : CR · 2023
    Review
  17. Review
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  19. Article
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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

19 authors at 10 institutions in 3 countries.

I BranaPrincess Margaret Cancer Centre, Toronto, Ontario, Canada.
R BergerSheba Medical Center, Ramat Gan, Israel.
T GolanSheba Medical Center, Ramat Gan, Israel.
P HaluskaMayo Clinic, Rochester, MN, USA.
J EdenfieldGreenville Health System - Cancer Institute, Greenville, SC, USA.
J FioricaSarasota Memorial Hospital, Sarasota, FL, USA.
J StephensonGreenville Health System - Cancer Institute, Greenville, SC, USA.
L P MartinFox Chase Cancer Center, Philadelphia, PA, USA.
S WestinUniversity of Texas - MD Anderson Cancer Center, Houston, TX, USA.
P HanjaniAbington Memorial Hospital, Abington, PA, USA.
M B JonesMerck & Co., Inc., North Wales, PA, USA.
K AlmhannaH Lee Moffitt Cancer Center, Tampa, FL, USA.
R M WenhamH Lee Moffitt Cancer Center, Tampa, FL, USA.
D M Sullivan1] H Lee Moffitt Cancer Center, Tampa, FL, USA [2] M2Gen Tampa, Tampa, FL, USA.
W S DaltonM2Gen Tampa, Tampa, FL, USA.
A GunchenkoMerck & Co., Inc., North Wales, PA, USA.
J D ChengMerck & Co., Inc., North Wales, PA, USA.
L L SiuPrincess Margaret Cancer Centre, Toronto, Ontario, Canada.
J E GrayH Lee Moffitt Cancer Center, Tampa, FL, USA.
Moffitt Cancer Center · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USPrincess Margaret Cancer Centre · CAPrisma Health · USSheba Medical Center · ILAbington Memorial Hospital · USFox Chase Cancer Center · USMayo Clinic in Arizona · USSarasota Memorial Hospital · USThe University of Texas MD Anderson Cancer Center · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
Princess Margaret Phase I Consorium (PMP1C)UM1CA186644 · NCI · UNIVERSITY HEALTH NETWORK · PI Philippe Bedard, Kevin D Courtney · 2014 to 2026
$16.6M
Phase 2 Clinical Trials Program for Experimental Therapeutics Clinical Trials NetworkUM1CA186686 · NCI · MAYO CLINIC ROCHESTER · PI ADJEI, ALEX A. · 2014 to 2019
$5.3M
NCI NIH HHS P30 CA076292NCI NIH HHS UM1 CA186644NCI NIH HHS UM1 CA186686
6 · The paper itself

Abstract

backgroundTwo strategies to interrogate the insulin growth factor 1 receptor (IGF-1R) pathway were investigated: vertical inhibition with dalotuzumab and MK-2206 or ridaforolimus to potentiate PI3K pathway targeting and horizontal cross-talk inhibition with dalotuzumab and MK-0752 to exert effects against cellular proliferation, angiogenesis, and stem cell propagation.

methodsA phase I, multi-cohort dose escalation study was conducted in patients with advanced solid tumours. Patients received dalotuzumab (10 mg kg(-1)) and escalating doses of MK-2206 (90-200 mg) or escalating doses of dalotuzumab (7.5-10 mg kg(-1)) and MK-0752 (1800 mg) weekly. Upon maximum tolerated dose determination, patients with low-RAS signature, high-IGF1 expression ovarian cancer were randomised to dalotuzumab/MK-2206 versus dalotuzumab/ridaforolimus, whereas patients with high IGF1/low IGF2 expression colorectal cancer received dalotuzumab/MK-0752.

resultsA total of 47 patients were enrolled: 29 in part A (18 in the dalotuzumab/MK-2206 arm and 11 in the dalotuzumab/MK-0752 arm) and 18 in part B (6 in each arm). Dose-limiting toxicities (DLTs) for dalotuzumab/MK-2206 included grade 4 neutropenia and grade 3 serum sickness-like reaction, maculopapular rash, and gastrointestinal inflammation. For dalotuzumab/MK-0752, DLTs included grade 3 dehydration, rash, and diarrhoea. Seven patients remained on study for >4 cycles.

conclusionsDalotuzumab/MK-2206 and dalotuzumab/MK-0752 combinations were tolerable. Further developments of prospectively validated predictive biomarkers to aid in patient selection for anti-IGF-1R therapies are needed.

Indexed as

AdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBenzene DerivativesBiomarkers, TumorClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicCohort StudiesFemaleFollow-Up StudiesHeterocyclic Compounds, 3-RingHumansMale3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acidAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBenzene DerivativesBiomarkers, TumordalotuzumabHeterocyclic Compounds, 3-RingMK 2206MTOR protein, humanPropionatesProto-Oncogene Proteins c-aktReceptor, IGF Type 1Receptors, NotchridaforolimusSirolimusSulfonesTOR Serine-Threonine Kinases

Identifiers

PMID25290091
PMCPMC4229637
OpenAlexW2006827588

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

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.