Hormone Receptor Positive endometrIal Carcinoma Treated by Dual mTORC1/mTORC2 Inhibitor and Anastrozole (VICTORIA)


The investigators hypothesize that the dual inhibition of mTORC1/mTORC2 by AZD2014 combined with inhibition of aromatase enzyme by anastrozole will act synergistically and may be an interesting therapeutic option for endometrial cancer with a manageable toxicity profile. The investigators proposal is to conduct a multicenter, 2-step, randomized, Phase I/II trial to evaluate the safety and efficacy of a combination treatment associating anastrozole to AZD2014 in advanced endometrial cancer patients. The study is divided in 2 steps : – A safety run-in phase aiming to evaluate the safety of the proposed combination AZD2014 + anastrozole (Arm A) versus anastrozole alone (Arm B). No dose escalation is scheduled (doses are based on maximum tolerated dose (MTD) defined for AZD2014 and the summary of product characteristics (SPC) of anastrozole). However, dose de-escalation for AZD2014 will be applied in case of toxicity. – A two-stage randomized Phase II part aiming to evaluate the clinical benefit of the AZD2014 + anastrozole (Arm A) combination therapy versus anastrozole (Arm B).

Full Title of Study: “A Multicentric, Randomized, Non Comparative, Open-label Phase I/II Evaluating AZD2014 (Dual Mammalian Target of Rapamycin Complex 1/2 (mTORC1/mTORC2) Inhibitor) in Combination With Anastrozole Versus Anastrozole Alone in the Treatment of Metastatic Hormone Receptor-positive Endometrial Adenocarcinoma”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2019

Detailed Description

TREATMENT PLAN : Following randomisation patients will receive Arm A : AZD2014 plus anastrozole or Arm B: anastrozole alone AZD2014 will be administered with an intermittent schedule i.e. 125 mg bis in die (BID) intermittent with 2 days on followed by 5 days off per week for a total weekly dose of 500 mg/week (250mg D1 and D2, 5 days off) Anastrozole will be administered at the standard dose defined in the SPC i.e. 1mg/d, per os, continuously. Both treatment will be administered until progressive disease (PD), unacceptable toxicity or willingness to stop. STATISTICS : A total of 72 patients will be randomized in the study. Safety run-in Phase on the first 9 patients randomized – As no dose escalation will be performed, the safety will be evaluated following the treatment and 8-week follow-up of the first 6 patients by the experimental association AZD2014+anastrozole (experimental arm). By similarity to a classic 3+3 design, based on binomial probabilities, there is a 90% probability of observing one or more patients with a toxicity event, if that event occurs in at least 32% of the target population. Assuming a 2:1 randomization ratio, a total of 9 patients (Arm A – Experimental: 6 patients, Arm B – Control: 3 patients) will be enrolled in this safety run-in phase and will be included in the evaluation of Phase II part. Phase II The sample size calculation was based on a Simon optimal two-stage design, with a minimum success (8-week non progression) rate considered of interest p1=60% and an uninteresting rate p0=40%. Assuming a type I error alpha of 0.05 and 80% power, 46 evaluable patients are needed in the experimental arm to reject the null hypothesis H0: p≤p0 versus the alternative hypothesis H1: p ≥ p1 in a unilateral situation (16 patients in Stage I and 30 additional patients in Stage II). With a 2:1 randomization and based on the assumption that 5% of the patients may be non-evaluable, a total of 72 patients will be included in the study : 48 patients in Arm A - experimental and 24 patients in Arm B – control). DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. serious adverse event (SAE) reporting will be also paper-based by e-mail and/or Fax. The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements.


  • Drug: AZD2014
    • Following inclusion, patients will be randomized (2:1) to receive Arm A : AZD2014 + anastrozole Arm B : anastrozole alone Mode of Action Selective and specific mTOR kinase inhibitor targeting both mTORC1 and mTORC2 complexes. Route of Administration Oral Dosage regimen 125mg BID with intermittent schedule (2 days of treatment followed by 5 days off (500mg/week)) Duration of treatment Until the patient experiences unacceptable toxicity, disease progression and/or treatment is discontinued per patient or investigator request.
  • Drug: Anastrozole
    • Therapeutic Class Aromatase inhibitor Mode of Action Potent and highly selective non-steroidal aromatase inhibitor. Route of Administration Oral Dosage regimen 1 mg tablet once a day Duration of treatment Patients may continue treatment with anastrozole until the patient experiences unacceptable toxicity, disease progression and/or treatment is discontinued per patient or investigator request.

Arms, Groups and Cohorts

  • Experimental: Arm A: AZD2014 plus anastrozole
  • Active Comparator: Arm B: anastrozole alone

Clinical Trial Outcome Measures

Primary Measures

  • Number of patients with severe toxicities occurring during the first 8 weeks of follow-up assessed using National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) V4
    • Time Frame: during the first 8 weeks of follow up
    • Severe toxicities defined as Any grade ≥ 4 treatment related toxicity Any grade≥ 3 treatment related toxicity lasting more than 7 days
  • The 8-week non progression rate using RECIST v1.1 to assess tumor response to treatment
    • Time Frame: 8 weeks after start of treatment

Secondary Measures

  • Number of patients with AE graded using CTCAE V4
    • Time Frame: For each participant, up to 30 days after the last dose of treatment (up to 3 years)
  • Progression-free survival (PFS) defined as the duration of time from start of treatment to time of progression or death, whichever occurs first
    • Time Frame: up to 3 years
  • Overall survival (OS) defined as the duration of time from start of treatment to time of death.
    • Time Frame: 3 years
  • Best response rate defined as (percentage of patients with complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) according to RECIST V1.1)
    • Time Frame: Up to 3 years
  • Duration of objective response as per RECIST v1.1
    • Time Frame: Up to 3 years
  • Area under the curve (AUC) of AZD2014
    • Time Frame: Week 1 Day 1: pre-dose, 2h and 6-8 hours later and Week 2 Day 1: pre-dose, 2h and 6-8 hours later.
  • Apparent clearance of AZD2014
    • Time Frame: Week 1 Day 1: pre-dose, 2h and 6-8 hours later and Week 2 Day 1: pre-dose, 2h and 6-8 hours later
  • The accumulation of the 47S precursor ribosomal ribonucleic acid (rRNA), which reflects RNA polymerase I activity analysed by fluorescence in situ hybridization (FISH)
    • Time Frame: Baseline and 8 weeks after treatment
  • The expression of components of rRNA methylation complex analysed by real time quantitative PCR (RTqPCR)
    • Time Frame: Baseline and 8 weeks after treatment
  • The levels of circulating anti-fibrillarin (anti-FBL) autoantibody on serum samples by Elisa assays
    • Time Frame: Baseline and 8 weeks after treatment
  • Levels of expression of fibrillarin assessed by immunohistochemistry (IHC)
    • Time Frame: Baseline and 8 weeks after treatment
  • Levels of expression of nucleolin assessed by IHC
    • Time Frame: Baseline and 8 weeks after treatment
  • Levels of expression of protein B23 assessed by IHC
    • Time Frame: Baseline and 8 weeks after treatment
  • Levels of expression of upstream binding factor (UBF) assessed by IHC
    • Time Frame: Baseline and 8 weeks after treatment
  • Levels of expression of phosphorylated UBF assessed by IHC
    • Time Frame: Baseline and 8 weeks after treatment

Participating in This Clinical Trial

Inclusion Criteria

  • Postmenopausal female patient at the time of consent – Histologically-confirmed diagnosis of advanced or recurrent endometrial carcinoma, not amenable to curative treatments. Carcinosarcoma are not eligible. – Documented estrogen receptor and/or progesterone receptor positive endometrial cancer. Hormone receptor positivity is defined according to routine practice at each participating site. – Availability of a pre-treatment tumor sample (archival formalin-fixed paraffin-embedded (FFPE) block or fresh biopsy if feasible) and presence of at least one biopsiable tumor lesion for on-treatment biopsy – Documented disease progression after no more than one prior first-line chemotherapy regimen and/or more than 2 lines endocrine therapy in the metastatic setting – Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 and minimum life expectancy of 8 weeks – At least one measurable lesion according to response evaluation criteria in solid tumor (RECIST 1.1) – Adequate bone marrow, renal and liver function as shown by: – Absolute neutrophil count > 1.5 x 109/L, Platelets > 100 x 109/L, Hemoglobin (Hb) >9 g/dL – Serum bilirubin ≤ 1.5 upper limit of normal (ULN), alanine aminotransferase and aspartate aminotransferase ≤ 2.5 ULN (≤ 5 ULN in patients with liver metastases) – Creatinine clearance > 50 mL/min (using Cockcroft formula, or MDRD formula for patients over 65 years Appendix 3 – Creatinine Clearance) – Fasting serum cholesterol ≤ 300 mg/dL (7.75 mmol/L) AND fasting triglycerides ≤ 2.5 ULN (lipid-lowering drugs allowed), – Fasting plasma glucose ≤7 mmol/L (126 mg/dL) – Recovered from prior significant treatment-related toxicity i.e. no persistent treatment-related toxicity > Grade 1 as per Common Terminology Criteria for Adverse Events (CTCAE) v4.3, except grade 2 alopecia, grade 2 anemia but with Hb >9 g/dL. – Minimal wash-out period before the start of the study drugs for the following treatments: – Any anti-cancer treatment approved or investigational medicinal product :> 21 days – Any chemotherapy, radiation therapy, androgens : > 21 days (not including palliative radiotherapy at focal sites). – Any monoclonal antibody therapy: > 4 weeks – Major surgery: > 4 weeks – Minor surgery (excluding tumour biopsies) >14 days. – Any haemopoietic growth factors (e.g., filgrastim [granulocyte colony-stimulating factor (G-CSF)], sargramostim [granulocyte-macrophage colony-stimulating factor (GM-CSF)]): > 14 days – Vaccinated with live, attenuated vaccines : > 4 weeks. – Sensitive or narrow therapeutic range substrates of drug transporters OATP1B1, OATP1B3, MATE1 and MATE2K: see the appropriate wash-out period (a minimum of 5 x reported elimination half-life) in Appendix 5 – Restricted CYP and transporter related co-medications – Potent or moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) and BCRP - Restricted CYP and transporter related co-medications – Patient willing to follow sunlight-protection measures. Patients should be advised of the need for sunlight protection measures during administration of AZD2014, and should be advised to adopt such measures for a period of 3 months after receiving their final dose of AZD2014. – Patient able and willing to provide informed consent with ability to understand and willingness for follow-up visits. – Covered by a medical insurance Exclusion Criteria:

  • Patient pre-treated by a non-steroidal aromatase inhibitor – Active uncontrolled or symptomatic central nervous system metastases or spinal cord compression – Clinically relevant abnormal levels of potassium or sodium. – Use of any forbidden concomitant treatment during the treatment period: – Any anti-cancer treatment (approved or investigational) not mentioned in the protocol – Chronic treatment with corticosteroids or other immunosuppressive agents. Stable low dose of corticosteroids are allowed (unless contra-indicated) provided that they were initiated before the last disease progression or were started at least 4 weeks prior to study treatment. Topical or inhaled corticosteroids are allowed. – Potent or moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) and BCRP (see Appendix 5 – Restricted CYP and transporter related co-medications) – Sensitive or narrow therapeutic range substrates of the drug transporters OATP1B1, OATP1B3, MATE1 and MATE2K outside the wash out period and restrictions presented in Appendix 5 – Restricted CYP and transporter related co-medications) – Patient with known hypersensitivity to anastrozole or to any of the excipients (Lactose monohydrate, Povidone, Sodium starch glycollate, Magnesium stearate, Hypromellose, Macrogol 300, Titanium dioxide) – History of hypersensitivity to active or inactive excipients of AZD2014 or drugs with a similar chemical structure or class to AZD2014 – History of other malignancies except for basal cell or squamous cell skin cancer, in situ cervical cancer, unless they have been disease-free for at least five years – Patient who has any severe and/or uncontrolled medical conditions such as: – Recent history of specific cardiovascular events, or laboratory parameters that may affect cardiac parameters including : unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease; Symptomatic congestive heart failure of New York heart Association Class III or IV – Haemorrhagic or thrombotic stroke, including transient ischemic attack (TIA) or any other CNS bleeding. – Mean resting corrected QT interval (QTc), calculated using Fridericia's formula, > 470 msec obtained from 3 electrocardiograms (ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes within 12 months of the patient entering in the study – Abnormal cardiac function at baseline :left ventricular ejection fraction (LVEF) <50% – Any evidence of interstitial lung disease and uncompensated respiratory conditions. – Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active or chronic hepatitis (i.e. quantifiable hepatitis B virus (HBV-DNA) and/or positive HbsAg, quantifiable hepatitis C virus (HCV-RNA)), – Active, bleeding diathesis – Current refractory nausea and vomiting, chronic gastro-intestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD2014. – Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption – Type 1 and uncontrolled Type 2 diabetes – Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis.

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Centre Leon Berard
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Pierre-Etienne HEUDEL, MD, Principal Investigator, Centre Leon Berard


Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983 Feb;15(1):10-7.

Levine DA, Hoskins WJ. Update in the management of endometrial cancer. Cancer J. 2002 May-Jun;8 Suppl 1:S31-40. Review.

Murali R, Soslow RA, Weigelt B. Classification of endometrial carcinoma: more than two types. Lancet Oncol. 2014 Jun;15(7):e268-78. doi: 10.1016/S1470-2045(13)70591-6. Review.

Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, Heintz AP, Ngan HY, Pecorelli S. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006 Nov;95 Suppl 1:S105-43.

Sonoda Y. Optimal therapy and management of endometrial cancer. Expert Rev Anticancer Ther. 2003 Feb;3(1):37-47. Review.

Decruze SB, Green JA. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int J Gynecol Cancer. 2007 Sep-Oct;17(5):964-78. Epub 2007 Apr 18. Review.

Kokka F, Brockbank E, Oram D, Gallagher C, Bryant A. Hormonal therapy in advanced or recurrent endometrial cancer. Cochrane Database Syst Rev. 2010 Dec 8;(12):CD007926. doi: 10.1002/14651858.CD007926.pub2. Review.

Rose PG, Brunetto VL, VanLe L, Bell J, Walker JL, Lee RB. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2000 Aug;78(2):212-6.

Diaz-Padilla I, Duran I, Clarke BA, Oza AM. Biologic rationale and clinical activity of mTOR inhibitors in gynecological cancer. Cancer Treat Rev. 2012 Oct;38(6):767-75. doi: 10.1016/j.ctrv.2012.02.001. Epub 2012 Feb 29. Review.

Slomovitz BM, Coleman RL. The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res. 2012 Nov 1;18(21):5856-64. doi: 10.1158/1078-0432.CCR-12-0662. Epub 2012 Oct 18. Review.

Oza AM, Elit L, Tsao MS, Kamel-Reid S, Biagi J, Provencher DM, Gotlieb WH, Hoskins PJ, Ghatage P, Tonkin KS, Mackay HJ, Mazurka J, Sederias J, Ivy P, Dancey JE, Eisenhauer EA. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J Clin Oncol. 2011 Aug 20;29(24):3278-85. doi: 10.1200/JCO.2010.34.1578. Epub 2011 Jul 25.

Slomovitz BM, Jiang Y, Yates MS, Soliman PT, Johnston T, Nowakowski M, Levenback C, Zhang Q, Ring K, Munsell MF, Gershenson DM, Lu KH, Coleman RL. Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol. 2015 Mar 10;33(8):930-6. doi: 10.1200/JCO.2014.58.3401. Epub 2015 Jan 26.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.

Trimble EL, Harlan LC, Clegg LX, Stevens JL. Pre-operative imaging, surgery and adjuvant therapy for women diagnosed with cancer of the corpus uteri in community practice in the United States. Gynecol Oncol. 2005 Mar;96(3):741-8.

Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, Wolk A, Wentzensen N, Weiss NS, Webb PM, van den Brandt PA, van de Vijver K, Thompson PJ; Australian National Endometrial Cancer Study Group, Strom BL, Spurdle AB, Soslow RA, Shu XO, Schairer C, Sacerdote C, Rohan TE, Robien K, Risch HA, Ricceri F, Rebbeck TR, Rastogi R, Prescott J, Polidoro S, Park Y, Olson SH, Moysich KB, Miller AB, McCullough ML, Matsuno RK, Magliocco AM, Lurie G, Lu L, Lissowska J, Liang X, Lacey JV Jr, Kolonel LN, Henderson BE, Hankinson SE, Håkansson N, Goodman MT, Gaudet MM, Garcia-Closas M, Friedenreich CM, Freudenheim JL, Doherty J, De Vivo I, Courneya KS, Cook LS, Chen C, Cerhan JR, Cai H, Brinton LA, Bernstein L, Anderson KE, Anton-Culver H, Schouten LJ, Horn-Ross PL. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol. 2013 Jul 10;31(20):2607-18. doi: 10.1200/JCO.2012.48.2596. Epub 2013 Jun 3. Review.

Singh M, Zaino RJ, Filiaci VJ, Leslie KK. Relationship of estrogen and progesterone receptors to clinical outcome in metastatic endometrial carcinoma: a Gynecologic Oncology Group Study. Gynecol Oncol. 2007 Aug;106(2):325-33. Epub 2007 May 25.

Kauppila A. Progestin therapy of endometrial, breast and ovarian carcinoma. A review of clinical observations. Acta Obstet Gynecol Scand. 1984;63(5):441-50. Review.

Lentz SS, Brady MF, Major FJ, Reid GC, Soper JT. High-dose megestrol acetate in advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 1996 Feb;14(2):357-61.

Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A, Soper JT, Given FT. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol. 1999 Jun;17(6):1736-44.

Whitney CW, Brunetto VL, Zaino RJ, Lentz SS, Sorosky J, Armstrong DK, Lee RB; Gynecologic Oncology Group study. Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Jan;92(1):4-9.

Thigpen T, Brady MF, Homesley HD, Soper JT, Bell J. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2001 Jan 15;19(2):364-7.

Ma BB, Oza A, Eisenhauer E, Stanimir G, Carey M, Chapman W, Latta E, Sidhu K, Powers J, Walsh W, Fyles A. The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers–a study of the National Cancer Institute of Canada Clinical Trials Group. Int J Gynecol Cancer. 2004 Jul-Aug;14(4):650-8.

Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012 Apr 13;149(2):274-93. doi: 10.1016/j.cell.2012.03.017. Review.

Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. doi: 10.1056/NEJMoa1109653. Epub 2011 Dec 7.

Turina M, Christ-Crain M, Polk HC Jr. Diabetes and hyperglycemia: strict glycemic control. Crit Care Med. 2006 Sep;34(9 Suppl):S291-300. Review.

White DA, Camus P, Endo M, Escudier B, Calvo E, Akaza H, Uemura H, Kpamegan E, Kay A, Robson M, Ravaud A, Motzer RJ. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med. 2010 Aug 1;182(3):396-403. doi: 10.1164/rccm.200911-1720OC. Epub 2010 Mar 1.

Albiges L, Chamming's F, Duclos B, Stern M, Motzer RJ, Ravaud A, Camus P. Incidence and management of mTOR inhibitor-associated pneumonitis in patients with metastatic renal cell carcinoma. Ann Oncol. 2012 Aug;23(8):1943-1953. doi: 10.1093/annonc/mds115. Epub 2012 Jun 11. Review.

Ruggero D. Translational control in cancer etiology. Cold Spring Harb Perspect Biol. 2013 Feb 1;5(2). pii: a012336. doi: 10.1101/cshperspect.a012336. Review. Erratum in: Cold Spring Harb Perspect Biol. 2012 Nov;4(11). doi:10.1101/cshperspect.a015891.

Elagöz S, Aricí DS, Aker H. Relationship between FIGO grade and AgNOR, S100-positive langerhans cells in endometrial adenocarcinoma. Pathol Int. 2000 Aug;50(8):616-9.

Trerè D, Melchiorri C, Chieco P, Marabini A, Derenzini M. Interphase AgNOR quantity and DNA content in endometrial adenocarcinoma. Gynecol Oncol. 1994 May;53(2):202-7.

Giuffrè G, Fulcheri E, Gualco M, Fedele F, Tuccari G. Standardized AgNOR analysis as a prognostic parameter in endometrial carcinoma, endometrioid type. Anal Quant Cytol Histol. 2001 Feb;23(1):31-9.

Belin S, Beghin A, Solano-Gonzàlez E, Bezin L, Brunet-Manquat S, Textoris J, Prats AC, Mertani HC, Dumontet C, Diaz JJ. Dysregulation of ribosome biogenesis and translational capacity is associated with tumor progression of human breast cancer cells. PLoS One. 2009 Sep 25;4(9):e7147. doi: 10.1371/journal.pone.0007147.

Marcel V, Ghayad SE, Belin S, Therizols G, Morel AP, Solano-Gonzàlez E, Vendrell JA, Hacot S, Mertani HC, Albaret MA, Bourdon JC, Jordan L, Thompson A, Tafer Y, Cong R, Bouvet P, Saurin JC, Catez F, Prats AC, Puisieux A, Diaz JJ. p53 acts as a safeguard of translational control by regulating fibrillarin and rRNA methylation in cancer. Cancer Cell. 2013 Sep 9;24(3):318-30. doi: 10.1016/j.ccr.2013.08.013.

Choi YW, Kim YW, Bae SM, Kwak SY, Chun HJ, Tong SY, Lee HN, Shin JC, Kim KT, Kim YJ, Ahn WS. Identification of differentially expressed genes using annealing control primer-based GeneFishing in human squamous cell cervical carcinoma. Clin Oncol (R Coll Radiol). 2007 Jun;19(5):308-18. Epub 2007 Apr 2.

Su H, Xu T, Ganapathy S, Shadfan M, Long M, Huang TH, Thompson I, Yuan ZM. Elevated snoRNA biogenesis is essential in breast cancer. Oncogene. 2014 Mar 13;33(11):1348-58. doi: 10.1038/onc.2013.89. Epub 2013 Apr 1.

Hein N, Hannan KM, George AJ, Sanij E, Hannan RD. The nucleolus: an emerging target for cancer therapy. Trends Mol Med. 2013 Nov;19(11):643-54. doi: 10.1016/j.molmed.2013.07.005. Epub 2013 Aug 15. Review.

Burger K, Mühl B, Harasim T, Rohrmoser M, Malamoussi A, Orban M, Kellner M, Gruber-Eber A, Kremmer E, Hölzel M, Eick D. Chemotherapeutic drugs inhibit ribosome biogenesis at various levels. J Biol Chem. 2010 Apr 16;285(16):12416-25. doi: 10.1074/jbc.M109.074211. Epub 2010 Feb 16.

Bywater MJ, Poortinga G, Sanij E, Hein N, Peck A, Cullinane C, Wall M, Cluse L, Drygin D, Anderes K, Huser N, Proffitt C, Bliesath J, Haddach M, Schwaebe MK, Ryckman DM, Rice WG, Schmitt C, Lowe SW, Johnstone RW, Pearson RB, McArthur GA, Hannan RD. Inhibition of RNA polymerase I as a therapeutic strategy to promote cancer-specific activation of p53. Cancer Cell. 2012 Jul 10;22(1):51-65. doi: 10.1016/j.ccr.2012.05.019.

Silvera D, Formenti SC, Schneider RJ. Translational control in cancer. Nat Rev Cancer. 2010 Apr;10(4):254-66. doi: 10.1038/nrc2824. Review.

Hannan KM, Brandenburger Y, Jenkins A, Sharkey K, Cavanaugh A, Rothblum L, Moss T, Poortinga G, McArthur GA, Pearson RB, Hannan RD. mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF. Mol Cell Biol. 2003 Dec;23(23):8862-77.

Iadevaia V, Liu R, Proud CG. mTORC1 signaling controls multiple steps in ribosome biogenesis. Semin Cell Dev Biol. 2014 Dec;36:113-20. doi: 10.1016/j.semcdb.2014.08.004. Epub 2014 Aug 19. Review.

Peltonen K, Colis L, Liu H, Trivedi R, Moubarek MS, Moore HM, Bai B, Rudek MA, Bieberich CJ, Laiho M. A targeting modality for destruction of RNA polymerase I that possesses anticancer activity. Cancer Cell. 2014 Jan 13;25(1):77-90. doi: 10.1016/j.ccr.2013.12.009.

Woiwode A, Johnson SA, Zhong S, Zhang C, Roeder RG, Teichmann M, Johnson DL. PTEN represses RNA polymerase III-dependent transcription by targeting the TFIIIB complex. Mol Cell Biol. 2008 Jun;28(12):4204-14. doi: 10.1128/MCB.01912-07. Epub 2008 Apr 7.

Whittaker S, Martin M, Marais R. All roads lead to the ribosome. Cancer Cell. 2010 Jul 13;18(1):5-6. doi: 10.1016/j.ccr.2010.06.008.

Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013 Aug;10(8):472-84. doi: 10.1038/nrclinonc.2013.110. Epub 2013 Jul 9. Review.

Dawson SJ, Rosenfeld N, Caldas C. Circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013 Jul 4;369(1):93-4. doi: 10.1056/NEJMc1306040.

Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin SF, Kingsbury Z, Wong AS, Marass F, Humphray S, Hadfield J, Bentley D, Chin TM, Brenton JD, Caldas C, Rosenfeld N. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013 May 2;497(7447):108-12. doi: 10.1038/nature12065. Epub 2013 Apr 7.

Frenel JS, Carreira S, Goodall J, Roda D, Perez-Lopez R, Tunariu N, Riisnaes R, Miranda S, Figueiredo I, Nava-Rodrigues D, Smith A, Leux C, Garcia-Murillas I, Ferraldeschi R, Lorente D, Mateo J, Ong M, Yap TA, Banerji U, Gasi Tandefelt D, Turner N, Attard G, de Bono JS. Serial Next-Generation Sequencing of Circulating Cell-Free DNA Evaluating Tumor Clone Response To Molecularly Targeted Drug Administration. Clin Cancer Res. 2015 Oct 15;21(20):4586-96. doi: 10.1158/1078-0432.CCR-15-0584. Epub 2015 Jun 17.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.