Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2019
Autophagy Inhibition to Augment mTOR Inhibition: a Phase I/II Trial of Everolimus and Hydroxychloroquine in Patients with Previously Treated Renal Cell Carcinoma.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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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.
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Who cites it
103 citing papers in PubMed, 148 citations in OpenAlex.
- BAMM (BRAF Autophagy and MEK Inhibition in Melanoma): A Phase I/II Trial of Dabrafenib, Trametinib, and Hydroxychloroquine in Advanced BRAFV600-mutant Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Renal cell carcinoma: molecular understanding and therapeutic development.Cell death and differentiation · 2026Review
- Clinical Outcomes, Treatment Patterns, and Molecular Heterogeneity of TFE3-Rearranged Renal Cell Carcinoma: A Multicenter Real-World Study.Cancer medicine · 2026Article
- Drug repurposing as a promising therapeutic strategy against renal cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- Autophagy-Apoptosis Crosstalk in Cancer: Mechanisms, Signaling Pathways, and Therapeutic Targeting.Cancers · 2026Review
- Targeting the ferritinophagy-lysosome axis as a therapeutic vulnerability in gastroenteropancreatic neuroendocrine tumors.Cell reports. Medicine · 2026Article
- Mechanisms Underlying Cancer Chemoresistance: A Starting Point to Identify New Anticancer Strategies.International journal of molecular sciences · 2026Article
- The multifaceted functions of selective autophagy in cancer: molecular basis, consequences, and clinical prospects.Molecular cancer · 2026Review
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- Cystinosis and Cellular Energy Failure: Mitochondria at the Crossroads.International journal of molecular sciences · 2026Review
- Berbamine sensitizes hepatocellular carcinoma to chemotherapy by inhibiting autophagyFrontiers in pharmacology · 2026Article
- Unraveling autophagy-metabolism crosstalk in cancer: Molecular insights and therapeutic strategies.Theranostics · 2026Review
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- Sevoflurane Exposure Exacerbates Memory Impairment and Pathological Manifestation by Inhibiting AKT/mTOR-Mediated Autophagy in P301L Tau Transgenic Mice.CNS neuroscience & therapeutics · 2025Article
- An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.Molecular pharmacology · 2025Review
- TSC2-mutated perivascular epithelioid cell tumor with partial response to mTOR inhibition: a case report and literature review.Discover oncology · 2025Article
- DSS1 inhibits autophagy to activate epithelial-mesenchymal transition in a pro-metastatic niche of renal cell carcinoma.Nature communications · 2025Article
- Autophagy inhibition potentiates anti-cancer activity of Sunitinib in kidney cancer cells.Biology direct · 2025Article
- A model-free phase I/II dose optimization design for immunotherapy trials.Statistical methods in medical research · 2025Article
- Cell-Type-Specific Autophagy in Human Leukocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
purposeEverolimus inhibits the mTOR, activating cytoprotective autophagy. Hydroxychloroquine inhibits autophagy. On the basis of preclinical data demonstrating synergistic cytotoxicity when mTOR inhibitors are combined with an autophagy inhibitor, we launched a clinical trial of combined everolimus and hydroxychloroquine, to determine its safety and activity in patients with clear-cell renal cell carcinoma (ccRCC). PATIENTS AND
methodsThree centers conducted a phase I/II trial of everolimus 10 mg daily and hydroxychloroquine in patients with advanced ccRCC. The objectives were to determine the MTD of hydroxychloroquine with daily everolimus, and to estimate the rate of 6-month progression-free survival (PFS) in patients with ccRCC receiving everolimus/hydroxychloroquine after 1-3 prior treatment regimens. Correlative studies to identify patient subpopulations that achieved the most benefit included population pharmacokinetics, measurement of autophagosomes by electron microscopy, and next-generation tumor sequencing.
resultsNo dose-limiting toxicity was observed in the phase I trial. The recommended phase II dose of hydroxychloroquine 600 mg twice daily with everolimus was identified. Disease control [stable disease + partial response (PR)] occurred in 22 of 33 (67%) evaluable patients. PR was observed in 2 of 33 patients (6%). PFS ≥ 6 months was achieved in 15 of 33 (45%) of patients who achieved disease control.
conclusionsCombined hydroxychloroquine 600 mg twice daily with 10 mg daily everolimus was tolerable. The primary endpoint of >40% 6-month PFS rate was met. Hydroxychloroquine is a tolerable autophagy inhibitor in future RCC or other trials.
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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.