Trial reportJournal of translational medicine2012
Phase II study of the farnesyltransferase inhibitor R115777 in advanced melanoma (CALGB 500104).
Trial report in Journal of translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00060125 (PHASE II TRIAL OF R115777 IN PATIENTS WITH METASTATIC MALIGNANT MELANOMA), which is not on this map. Cited by 39 papers, 2 of them syntheses that pooled 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.
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.
Phase ii trial of r115777 in patients with metastatic malignant melanoma
Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Mutational Characteristics of Primary Mucosal Melanoma: A Systematic Review.Molecular diagnosis & therapy · 2022Pooled it
- Guidelines for biomarker testing in metastatic melanoma: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2014Guideline
- A phase I study of the farnesyltransferase inhibitor Tipifarnib in combination with the epidermal growth factor tyrosine kinase inhibitor Erlotinib in patients with advanced solid tumors.Investigational new drugs · 2019Trial
- Randomized phase II trial of sorafenib with temsirolimus or tipifarnib in untreated metastatic melanoma (S0438).Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Dissecting the MAPK signaling landscape in malignant melanoma: from BRAF and NRAS mutations to precision combination therapies.Frontiers in cell and developmental biology · 2025Review
- A real-world study of adjuvant anti-PD -1 immunotherapy on stage III melanoma with BRAF, NRAS, and KIT mutations.Cancer medicine · 2023Article
- Melanoma Targeted Therapies beyondCancers · 2021Review
- Efficacy of Targeted Radionuclide Therapy Using [Cancers · 2021Article
- The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC).Cell reports. Medicine · 2021Review
- Novel insights into the pathogenesis and treatment of NRAS mutant melanoma.Expert review of precision medicine and drug development · 2021Article
- Current Perspectives and Novel Strategies ofOncoTargets and therapy · 2021Review
- Natural Products Attenuating Biosynthesis, Processing, and Activity of Ras Oncoproteins: State of the Art and Future Perspectives.Biomolecules · 2020Review
- Inhibition of NRAS Signaling in Melanoma through Direct Depalmitoylation Using Amphiphilic Nucleophiles.ACS chemical biology · 2020Article
- The MNK1/2-eIF4E Axis as a Potential Therapeutic Target in Melanoma.International journal of molecular sciences · 2020Review
- Non-BRAF Mutant Melanoma: Molecular Features and Therapeutical Implications.Frontiers in molecular biosciences · 2020Review
- Potential therapeutic targets of epithelial-mesenchymal transition in melanoma.Cancer letters · 2017Review
- Mechanisms of Chromosome Congression during Mitosis.Biology · 2017Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundMultiple farnesylated proteins are involved in signal transduction in cancer. Farnesyltransferase inhibitors (FTIs) have been developed as a strategy to inhibit the function of these proteins. As FTIs inhibit proliferation of melanoma cell lines, we undertook a study to assess the impact of a FTI in advanced melanoma. As farnesylated proteins are also important for T cell activation, measurement of effects on T cell function was also pursued.
methodsA 3-stage trial design was developed with a maximum of 40 patients and early stopping if there were no responders in the first 14, or fewer than 2 responders in the first 28 patients. Eligibility included performance status of 0-1, no prior chemotherapy, at most 1 prior immunotherapy, no brain metastases, and presence of at least 2 cutaneous lesions amenable to biopsy. R115777 was administered twice per day for 21 days of a 28-day cycle. Patients were evaluated every 2 cycles by RECIST. Blood and tumor were analyzed pre-treatment and during week 7.
resultsFourteen patients were enrolled. Two patients had grade 3 toxicities, which included myelosuppression, nausea/vomiting, elevated BUN, and anorexia. There were no clinical responses. All patients analyzed showed potent inhibition of FT activity (85-98%) in tumor tissue; inhibition of phosphorylated ERK and Akt was also observed. T cells showed evidence of FT inhibition and diminished IFN-γ production.
conclusionsDespite potent target inhibition, R115777 showed no evidence of clinical activity in this cohort of melanoma patients. Inhibition of T cell function by FTIs has potential clinical implications. Clinicaltrials.gov number NCT00060125.
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What OpenQuestion 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 OpenQuestion graph.