Study Evaluating Impact of IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients

Tracking Information
First Submitted Date ICMJE	June 6, 2011
First Posted Date ICMJE	June 7, 2011
Last Update Posted Date	February 9, 2015
Study Start Date ICMJE	June 2011
Actual Primary Completion Date	September 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 2, 2012)	to determine the optimal schedule to deliver CYT107 during chemotherapy based on restoration of CD4 count [ Time Frame: after 11 weeks of treatment ]; Evolution of CD4 count from Day 0 to Week 11 with repeated measures from D0 to W12 (D0, D21, D57, D78).
Original Primary Outcome Measures ICMJE; (submitted: June 6, 2011)	to determine the optimal schedule to deliver CYT107 during chemotherapy based on restoration of CD4 count [ Time Frame: after 12 weeks of treatment ]; Evolution of CD4 count from Day 0 to Week 12 with repeated measures from D0 to W12 (D0, D21, D63, D84).
Change History	Complete list of historical versions of study NCT01368107 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 2, 2012)	to determine if CYT107 treatment enables to reduce the incidence of severe haematological toxicity (any type of haematological toxicity Grade ≥ 3) post-chemotherapy [ Time Frame: at the end of study M12 ]; To assess the impact of CYT107 on progression-free survival [ Time Frame: at the end of study (M12) ]Time from randomisation to first evidence of progression or death of any cause.; To assess the impact of CYT107 on compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles). [ Time Frame: at the end of study (M12) ]Number of CT cycles, CT dose delays and/or reduction, CT discontinuation; To assess the impact of CYT107 on CD4 lymphopenia over the study period [ Time Frame: at the end of study (M12) ]Evolution of CD4 count from Day 0 to end of study visit; to evaluate if CYT107 treatment will selectively stimulate the proliferation and activation of peripheral immune subsets (analysis of phenotype and activation status of peripheral immune e sub-populations) [ Time Frame: D0, D21, D57, D78 and at end of study M12 ]Measure of frequency and activation status of circulating immune subpopulations on fresh whole blood. Multi-parametric marker sets (6-8 markers) will be used to analyse phenotype of immune subpopulations (TCD4+, TCD8+, Treg, T, NK, DC) and their activation status (PD1, ICOS, CD39, CD73, CD62L, CCR7, CD45RO, CD45RA, CD86).; to evaluate if CYT107 treatment will selectively improve the functional response of T cells, DC subsets and NK cells [ Time Frame: D0, D21, D57, D78 and at the end of study M12 ]Analysis of the functional response of T cells, DC subsets and NK cells; to evaluate if CYT107 treatment will is able to revert tolerogenic immune burden to increase specific anti-tumor response (measure of antigen specific CD8 response, measure of cytokine plasmatic levels) [ Time Frame: D0, D21, D57, D78 and at the end of study M12 ] Analysis of tumor associated antigen (TAA) specific CD8 responses Quantification of circulating cytokines including mainly, but not limited to, IL-6, IL-2, IFN, VEGF, TNF, IL-15,F FGF using Luminex technology and VEGF, TGF, IL-7R by Elisa.; to evaluate if CYT107 treatment will enable to increase TCR diversity (analysis of combinatorial diversity). [ Time Frame: D0, D21, D57, D78 and at the end of study M12 ]Evaluation of T cell receptor diversity using ImmuneTraCkeR test and Constel'ID software (ImmunID Technologies, Grenoble, France).; To assess the impact of CYT107 treatment on overall incidence of side effects [ Time Frame: after 12 weeks of treatment ]Number of patients with AEs (any type any grade) using NCI-CTCAE scale (version 4.0) from D0 to W12
Original Secondary Outcome Measures ICMJE; (submitted: June 6, 2011)	to determine if CYT107 treatment enables to reduce the incidence of severe haematological toxicity (any type of haematological toxicity Grade ≥ 3) post-chemotherapy [ Time Frame: at the end of study M12 ]; To assess the impact of CYT107 on progression-free survival [ Time Frame: at the end of study (M12) ]Time from randomisation to first evidence of progression or death of any cause.; To assess the impact of CYT107 on compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles). [ Time Frame: at the end of study (M12) ]Number of CT cycles, CT dose delays and/or reduction, CT discontinuation; To assess the impact of CYT107 on CD4 lymphopenia over the study period [ Time Frame: at the end of study (M12) ]Evolution of CD4 count from Day 0 to end of study visit; to evaluate if CYT107 treatment will selectively stimulate the proliferation and activation of peripheral immune subsets (analysis of phenotype and activation status of peripheral immune e sub-populations) [ Time Frame: D0, D21, D63, D184 and at end of study M12 ]Measure of frequency and activation status of circulating immune subpopulations on fresh whole blood. Multi-parametric marker sets (6-8 markers) will be used to analyse phenotype of immune subpopulations (TCD4+, TCD8+, Treg, T, NK, DC) and their activation status (PD1, ICOS, CD39, CD73, CD62L, CCR7, CD45RO, CD45RA, CD86).; to evaluate if CYT107 treatment will selectively improve the functional response of T cells, DC subsets and NK cells [ Time Frame: D0, D21, D63, D184 and at the end of study M12 ]Analysis of the functional response of T cells, DC subsets and NK cells; to evaluate if CYT107 treatment will is able to revert tolerogenic immune burden to increase specific anti-tumor response (measure of antigen specific CD8 response, measure of cytokine plasmatic levels) [ Time Frame: D0, D21, D63, D184 and at the end of study M12 ] Analysis of tumor associated antigen (TAA) specific CD8 responses Quantification of circulating cytokines including mainly, but not limited to, IL-6, IL-2, IFN, VEGF, TNF, IL-15,F FGF using Luminex technology and VEGF, TGF, IL-7R by Elisa.; to evaluate if CYT107 treatment will enable to increase TCR diversity (analysis of combinatorial diversity). [ Time Frame: D0, D21, D63, D184 and at the end of study M12 ]Evaluation of T cell receptor diversity using ImmuneTraCkeR test and Constel'ID software (ImmunID Technologies, Grenoble, France).; To assess the impact of CYT107 treatment on overall incidence of side effects [ Time Frame: after 12 weeks of treatment ]Number of patients with AEs (any type any grade) using NCI-CTCAE scale (version 4.0) from D0 to W12
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Study Evaluating Impact of IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients
Official Title ICMJE	A Randomised, Multicentric, Phase 2a Study Evaluating the Impact of an Immunotherapy by IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients
Brief Summary	The purpose of the study is to evaluate the impact of an immunotherapy by IL-7 on CD4 lymphopenia, risks of severe haematological toxicity and tumor progression in metastatic breast cancer patients. The primary objective is to determine the optimal schedule to deliver CYT107 during chemotherapy based on restoration of CD4 count. This study is a phase II, randomised, double-blind, placebo-controlled, single-centre. 24 patients will be included in the study.
Detailed Description	A key secondary objective is to determine if CYT107 treatment enables to reduce the incidence of severe haematological toxicity (any type of haematological toxicity Grade ≥ 3) post-chemotherapy. Other secondary objectives are to assess the impact of CYT107 treatment on the following parameters: Overall incidence of side effects (any type any grade); Progression-free survival (PFS); Compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles).; CD4 lymphopenia over the study period Exploratory biological markers A series of biomarkers analyses will be performed to evaluate if CYT107 treatment will: selectively stimulate the proliferation and activation of peripheral immune subsets (analysis of phenotype and activation status of peripheral immune e sub-populations); selectively improve the functional response of T cells, DC subsets and NK cells.; is able to revert tolerogenic immune burden to increase specific anti-tumor response (measure of antigen specific CD8 response, measure of cytokine plasmatic levels); enable to increase TCR diversity (analysis of combinatorial diversity).
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Metastatic Breast Cancer
Intervention ICMJE	Drug: placebo Placebo before the 1st (D0, D7, D14)and during the 3rd CT cycle (D57, D64, D71); Drug: interleukin 7 patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle (D0, D7, D14) and the placebo during the 3rd CT cycle (D57, D64, D71); Drug: interleukin 7 patients will receive the placebo before the 1st CT cycle (D0, D7, D14) and a delayed treatment with CYT107 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (D57, D64, D71); Drug: interleukin 7 patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle (D0, D7, D14) and a maintenance cycle of IL-7 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (D57, D64, D71)
Study Arms	Placebo Comparator: Placebo Arm the patients will receive Placebo before the 1st and during the 3rd CT cycle (N=6) Intervention: Drug: placebo; Experimental: CYT107 treatment before CT patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle and the placebo during the 3rd CT cycle (N=6) Interventions: Drug: placebo Drug: interleukin 7; Experimental: CYT107 treatment during CT patients will receive the placebo before the 1st CT cycle and a delayed treatment with CYT107 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (N=6) Intervention: Drug: interleukin 7; Experimental: CYT107 treatment before and during CT patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle and a maintenance cycle of IL-7 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (N=6). Intervention: Drug: interleukin 7
Publications *	Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006 Apr;6(4):295-307. Review.; Treilleux I, Blay JY, Bendriss-Vermare N, Ray-Coquard I, Bachelot T, Guastalla JP, Bremond A, Goddard S, Pin JJ, Barthelemy-Dubois C, Lebecque S. Dendritic cell infiltration and prognosis of early stage breast cancer. Clin Cancer Res. 2004 Nov 15;10(22):7466-74.; Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL, Banham AH. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006 Dec 1;24(34):5373-80.; Gobert M, Treilleux I, Bendriss-Vermare N, Bachelot T, Goddard-Leon S, Arfi V, Biota C, Doffin AC, Durand I, Olive D, Perez S, Pasqual N, Faure C, Ray-Coquard I, Puisieux A, Caux C, Blay JY, Ménétrier-Caux C. Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Res. 2009 Mar 1;69(5):2000-9. doi: 10.1158/0008-5472.CAN-08-2360. Epub 2009 Feb 24.; Blay JY, Chauvin F, Le Cesne A, Anglaret B, Bouhour D, Lasset C, Freyer G, Philip T, Biron P. Early lymphopenia after cytotoxic chemotherapy as a risk factor for febrile neutropenia. J Clin Oncol. 1996 Feb;14(2):636-43.; Blay JY, Le Cesne A, Mermet C, Maugard C, Ravaud A, Chevreau C, Sebban C, Guastalla J, Biron P, Ray-Coquard I. A risk model for thrombocytopenia requiring platelet transfusion after cytotoxic chemotherapy. Blood. 1998 Jul 15;92(2):405-10.; Ray-Coquard I, Le Cesne A, Rubio MT, Mermet J, Maugard C, Ravaud A, Chevreau C, Sebban C, Bachelot T, Biron P, Blay JY. Risk model for severe anemia requiring red blood cell transfusion after cytotoxic conventional chemotherapy regimens. The Elypse 1 Study Group. J Clin Oncol. 1999 Sep;17(9):2840-6.; Ray-Coquard I, Borg C, Bachelot T, Sebban C, Philip I, Clapisson G, Le Cesne A, Biron P, Chauvin F, Blay JY; ELYPSE study group. Baseline and early lymphopenia predict for the risk of febrile neutropenia after chemotherapy. Br J Cancer. 2003 Jan 27;88(2):181-6.; Marec-Berard P, Blay JY, Schell M, Buclon M, Demaret C, Ray-Coquard I. Risk model predictive of severe anemia requiring RBC transfusion after chemotherapy in pediatric solid tumor patients. J Clin Oncol. 2003 Nov 15;21(22):4235-8.; Borg C, Ray-Coquard I, Philip I, Clapisson G, Bendriss-Vermare N, Menetrier-Caux C, Sebban C, Biron P, Blay JY. CD4 lymphopenia as a risk factor for febrile neutropenia and early death after cytotoxic chemotherapy in adult patients with cancer. Cancer. 2004 Dec 1;101(11):2675-80.; Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, Tredan O, Verweij J, Biron P, Labidi I, Guastalla JP, Bachelot T, Perol D, Chabaud S, Hogendoorn PC, Cassier P, Dufresne A, Blay JY; European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009 Jul 1;69(13):5383-91. doi: 10.1158/0008-5472.CAN-08-3845. Epub 2009 Jun 23.; Fry TJ, Mackall CL. The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance. J Immunol. 2005 Jun 1;174(11):6571-6. Review.; Ménétrier-Caux C, Gobert M, Caux C. Differences in tumor regulatory T-cell localization and activation status impact patient outcome. Cancer Res. 2009 Oct 15;69(20):7895-8. doi: 10.1158/0008-5472.CAN-09-1642. Epub 2009 Oct 6. Review.; Fry TJ, Moniuszko M, Creekmore S, Donohue SJ, Douek DC, Giardina S, Hecht TT, Hill BJ, Komschlies K, Tomaszewski J, Franchini G, Mackall CL. IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates. Blood. 2003 Mar 15;101(6):2294-9. Epub 2002 Oct 31.; Fry TJ, Mackall CL. Interleukin-7: from bench to clinic. Blood. 2002 Jun 1;99(11):3892-904. Review.; Rosenberg SA, Sportès C, Ahmadzadeh M, Fry TJ, Ngo LT, Schwarz SL, Stetler-Stevenson M, Morton KE, Mavroukakis SA, Morre M, Buffet R, Mackall CL, Gress RE. IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother. 2006 May-Jun;29(3):313-9.; Sportès C, Hakim FT, Memon SA, Zhang H, Chua KS, Brown MR, Fleisher TA, Krumlauf MC, Babb RR, Chow CK, Fry TJ, Engels J, Buffet R, Morre M, Amato RJ, Venzon DJ, Korngold R, Pecora A, Gress RE, Mackall CL. Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med. 2008 Jul 7;205(7):1701-14. doi: 10.1084/jem.20071681. Epub 2008 Jun 23.; Akashi K, Kondo M, von Freeden-Jeffry U, Murray R, Weissman IL. Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Cell. 1997 Jun 27;89(7):1033-41.; Li WQ, Guszczynski T, Hixon JA, Durum SK. Interleukin-7 regulates Bim proapoptotic activity in peripheral T-cell survival. Mol Cell Biol. 2010 Feb;30(3):590-600. doi: 10.1128/MCB.01006-09. Epub 2009 Nov 23.; McFarland RD, Douek DC, Koup RA, Picker LJ. Identification of a human recent thymic emigrant phenotype. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4215-20.; Alpdogan O, van den Brink MR. IL-7 and IL-15: therapeutic cytokines for immunodeficiency. Trends Immunol. 2005 Jan;26(1):56-64. Review.; Melchionda F, Fry TJ, Milliron MJ, McKirdy MA, Tagaya Y, Mackall CL. Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool. J Clin Invest. 2005 May;115(5):1177-87. Epub 2005 Apr 7.; Jaleco S, Swainson L, Dardalhon V, Burjanadze M, Kinet S, Taylor N. Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis. J Immunol. 2003 Jul 1;171(1):61-8.; Sereti I, Dunham RM, Spritzler J, Aga E, Proschan MA, Medvik K, Battaglia CA, Landay AL, Pahwa S, Fischl MA, Asmuth DM, Tenorio AR, Altman JD, Fox L, Moir S, Malaspina A, Morre M, Buffet R, Silvestri G, Lederman MM; ACTG 5214 Study Team. IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Blood. 2009 Jun 18;113(25):6304-14. doi: 10.1182/blood-2008-10-186601. Epub 2009 Apr 20.; Levy Y, Lacabaratz C, Weiss L, Viard JP, Goujard C, Lelièvre JD, Boué F, Molina JM, Rouzioux C, Avettand-Fénoêl V, Croughs T, Beq S, Thiébaut R, Chêne G, Morre M, Delfraissy JF. Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest. 2009 Apr;119(4):997-1007. doi: 10.1172/JCI38052. Epub 2009 Mar 16.; Lévy Y, Sereti I, Tambussi G, Routy JP, Lelièvre JD, Delfraissy JF, Molina JM, Fischl M, Goujard C, Rodriguez B, Rouzioux C, Avettand-Fenoël V, Croughs T, Beq S, Morre M, Poulin JF, Sekaly RP, Thiebaut R, Lederman MM. Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study. Clin Infect Dis. 2012 Jul;55(2):291-300. doi: 10.1093/cid/cis383. Epub 2012 May 1.; 27. Miguel-Angel Perales, Jenna D. Goldberg,, Leuren Lechner Jianda Yuan, Esperanza Papadopoulos, James W. Young, Ann A. Jakubowski, Guenther Koehne, Humilidad Gallardo, Ryan Kendle, Cailian Liu, Teresa Rasalan, Yinyan Xu, Bushra Zaidi, Jedd D Wolchok, Therese Croughs, Michel Morre, Molly Maloy, Glenn Heller and Marcel R.M. van den Brink. Recombinant Human Interleukin-7 (CYT107) Enhances CD4 and CD8 T Cell Recovery Following T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplant In Patients with Myeloid Malignancies Oral and Poster Abstracts Oral Session: ASH 2010 Meeting.; Li B, VanRoey MJ, Jooss K. Recombinant IL-7 enhances the potency of GM-CSF-secreting tumor cell immunotherapy. Clin Immunol. 2007 May;123(2):155-65. Epub 2007 Feb 22.; Pellegrini M, Calzascia T, Elford AR, Shahinian A, Lin AE, Dissanayake D, Dhanji S, Nguyen LT, Gronski MA, Morre M, Assouline B, Lahl K, Sparwasser T, Ohashi PS, Mak TW. Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies. Nat Med. 2009 May;15(5):528-36. doi: 10.1038/nm.1953. Epub 2009 Apr 26. Erratum in: Nat Med. 2009 Jul;15(7):819.; McAlister FA, Straus SE, Sackett DL, Altman DG. Analysis and reporting of factorial trials: a systematic review. JAMA. 2003 May 21;289(19):2545-53. Review.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 6, 2011)	24
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	June 2014
Actual Primary Completion Date	September 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Female aged more than 18 years; Histologic diagnosis of metastatic breast cancer to be treated with capecitabine at study entry. NB: Patients previously treated with capecitabine are eligible only if more than 6 months have elapsed since the last capecitabine intake.; Lymphopenic (i.e. with at least one value of lymphocyte count 1500/µL within 15 days before Day 0).; Performance status ECOG of 0, 1,2 or 3; Life expectancy ≥ 6months; Adequate bone marrow, hepatic and renal function as follows: Neutrophils ≥ 1,000/µL Platelets ≥ 100 109/µL ASAT, ALAT, or Alkaline Phosphatase ≤ 2.5 x ULN Total Bilirubin ≤ 1.5 x ULN INR ≤ 1.5 Calculated creatinin clearance ≥ 60mL/min (Cockcroft formula or MDRD formula for patients older than 65 years old)- Ability to understand and sign informed consent; Covered by a medical insurance. Exclusion Criteria: Prior history of other malignancies other than breast cancer (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the subjects has been free of the disease for at least 3 years.; No resolution of specific toxicities related to any prior anti-cancer therapy to Grade ≤2 according to the NCI CTCAE v.4.0 (except lymphopenia, alopecia and neuropathy); Wash out period of less than 5 times the half-life of previous anti-cancer treatment before study entry, except if previous chemotherapy treatment before study entry. NB: For patient previously treated by hormonotherapy, a wash out period of 1 week will be sufficient; Uncontrolled hypertension (i.e., resting systolic blood pressure greater than140 mmHg or resting diastolic blood pressure greater than 90 mmHg), despite pharmacologic antihypertensive treatment, confirmed with a second blood pressure measurement done later in the same day; History of lymphoid malignancy (e.g. Hodgkin disease, non Hodgkin lymphoma, Leukemia).; History of splenectomy or hematologic disease associated with hypersplenism, such as gamma or beta-thalassemia, hereditary spherocytosis, Gaucher's disease, or autoimmune hemolytic anemia.; Any cardiac, pulmonary, thyroid, renal, hepatic, neurological severe/uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol; Any history of severe auto-immune disease; Hepatitis B antigen (HBs Ag) positive, Hepatitis C (HCV Ab) antibody positive or HCV RNA detectable; Documented HIV-1 positivity; History of cardiovascular disorders grade >2 (NYHA) within 6 months preceding the inclusion; Active uncontrolled viral, fungal or bacterial infection; Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements (participants must agree to refrain from substance abuse use during the entire course of the study); Pregnant or breast-feeding women; No use of effective birth control methods for women of childbearing potential; Any contraindications to capecitabine treatment (refer to Xeloda SPC Appendix 11) and to any other anti-cancer treatment authorized as per protocol (refer to respective SPC for specific contraindications)
Sex/Gender	Sexes Eligible for Study: Female
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	France
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01368107
Other Study ID Numbers ICMJE	ELYPSE 7; 2011-000226-30 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Centre Leon Berard
Study Sponsor ICMJE	Centre Leon Berard
Collaborators ICMJE	Ministry of Health, France; Cytheris, Inc.
Investigators ICMJE	Principal Investigator: Isabelle Ray Coquart Centre Léon Bérard, Lyon
PRS Account	Centre Leon Berard
Verification Date	December 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP