Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2015
Combination of the mTOR inhibitor ridaforolimus and the anti-IGF1R monoclonal antibody dalotuzumab: preclinical characterization and phase I clinical trial.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00730379 (A Phase I Study of Ridaforolimus), which is not on this map. Cited by 33 papers.
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.
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.
A Phase I Study of Ridaforolimus (MK8669) and MK0646 in Patients With Advanced Cancer
Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- XENERA-1: a randomised double-blind Phase II trial of xentuzumab in combination with everolimus and exemestane versus everolimus and exemestane in patients with hormone receptor-positive/HER2-negative metastatic breast cancer and non-visceral disease.Breast cancer research : BCR · 2023Trial
- Randomized, phase I/II study of gemcitabine plus IGF-1R antagonist (MK-0646) versus gemcitabine plus erlotinib with and without MK-0646 for advanced pancreatic adenocarcinoma.Journal of hematology & oncology · 2018Trial
- A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer.Breast cancer research and treatment · 2017Trial
- A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer.Breast cancer research and treatment · 2017Trial
- A phase II study of clinical activity of SCH 717454 (robatumumab) in patients with relapsed osteosarcoma and Ewing sarcoma.Pediatric blood & cancer · 2016Trial
- Review
- Unveiling the Role of Mechanistic Target of Rapamycin Kinase (MTOR) Signaling in Cancer Progression and the Emergence of MTOR Inhibitors as Therapeutic Strategies.ACS pharmacology & translational science · 2024Review
- Decoding the Role of Insulin-like Growth Factor 1 and Its Isoforms in Breast Cancer.International journal of molecular sciences · 2024Review
- Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review.Frontiers in pharmacology · 2024Review
- Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors.JAMA network open · 2023Article
- Obesity and endocrine-related cancer: The important role of IGF-1.Frontiers in endocrinology · 2023Review
- Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model.Frontiers in oncology · 2023Article
- The Insulin-like Growth Factor Signaling Pathway in Breast Cancer: An Elusive Therapeutic Target.Life (Basel, Switzerland) · 2022Review
- Modeling the Tumor Microenvironment and Pathogenic Signaling in Bone Sarcoma.Tissue engineering. Part B, Reviews · 2020Review
- Review
- Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer.Frontiers in cell and developmental biology · 2020Review
- Advances in insulin-like growth factor biology and -directed cancer therapeutics.Advances in cancer research · 2020Review
- Oncofoetal insulin receptor isoform A marks the tumour endothelium; an underestimated pathway during tumour angiogenesis and angiostatic treatment.British journal of cancer · 2019Article
- β-catenin/TCF activity regulates IGF-1R tyrosine kinase inhibitor sensitivity in colon cancer.Oncogene · 2018Article
- The association of diabetes mellitus and insulin treatment with expression of insulin-related proteins in breast tumors.BMC cancer · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeMammalian target of rapamycin (mTOR) inhibition activates compensatory insulin-like growth factor receptor (IGFR) signaling. We evaluated the ridaforolimus (mTOR inhibitor) and dalotuzumab (anti-IGF1R antibody) combination. EXPERIMENTAL
designIn vitro and in vivo models, and a phase I study in which patients with advanced cancer received ridaforolimus (10-40 mg/day every day × 5/week) and dalotuzumab (10 mg/kg/week or 7.5 mg/kg/every other week) were explored.
resultsPreclinical studies demonstrated enhanced pathway inhibition with ridaforolimus and dalotuzumab. With 87 patients treated in the phase I study, main dose-limiting toxicities (DLT) of the combination were primarily mTOR-related stomatitis and asthenia at doses of ridaforolimus lower than expected, suggesting blockade of compensatory pathways in normal tissues. Six confirmed partial responses were reported (3 patients with breast cancer); 10 of 23 patients with breast cancer and 6 of 11 patients with ER(+)/high-proliferative breast cancer showed antitumor activity.
conclusionsOur study provides proof-of-concept that inhibiting the IGF1R compensatory response to mTOR inhibition is feasible with promising clinical activity in heavily pretreated advanced cancer, particularly in ER(+)/high-proliferative breast cancer (ClinicalTrials.gov identifier: NCT00730379).
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.