Clinical trial NCT03673332: Elderly Cancer PatIents, Safety and qualiTy of Life Under immunOtheraPies
Official title: Elderly Cancer PatIents Treated for Advanced or Metastatic Melanoma or NSCLC, Safety and qualiTy of Life Under immunOtheraPies: a Phase IV Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Advanced or Metastatic Melanoma
Advanced or Metastatic NSCLC
Keywords: Elderly cancer patients
Immunotherapies
Lead sponsor: Institut Paoli-Calmettes
Sponsor class: OTHER
Collaborators: name: Société Francophone d'Onco-Gériatrie
First posted: 2018-09-17
Enrollment: 40
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a national prospective phase 4, multi-centre, single arm, open-label cohort study to evaluate the safety and efficacy of immune checkpoint inhibitors-based therapies in elderly patients with advanced or metastatic melanoma or NSCLC.
Primary purpose: TREATMENT

Brief summary: The co-primary objectives will be to assess the safety and quality of life under treatment.

Detailed description: The co-primary objectives will be to assess the safety and quality of life under treatment. Secondary objectives will be evaluations of geriatric data modifications under treatment, efficacy (progression-free survival and overall survival), correlation between toxicity and efficacy, and comparison of the safety profiles between various immunotherapy regimens.

Another secondary objective will be the comparison between patients and clinicians symptom reporting. The investigators will also perform a pharmacokinetics analysis on PD1-monoclonal antibodies to improve the understanding of PD-1 inhibitors pharmacokinetics for the elderly population.

Finally, toxicity and efficacy will be compared to immunological parameters such as the description of tumor infiltrating lymphocytes, markers of immunosenescence and inflammation.

Eligibility criteria: Inclusion Criteria:

* Patients eligible to start a treatment including immune checkpoint inhibitors (Nivolumab, Ipilimumab, Pembrolizumab, and so on...)
* Diagnosis of advanced or metastatic melanoma or NSCLC (All treatment lines will be allowed)
* Age ≥ 70 years
* Having personally signed and dated informed consent
* Patient affiliated to the ''National security'' regimen or beneficiary of this regimen

Exclusion Criteria:

* Immune checkpoint inhibitor therapy initiated before study enrolment
* Concomitant participation in other investigational clinical trials involving an immune checkpoint inhibitor
* Immune checkpoint inhibitor treatment in a context of other solid tumours
* Immune checkpoint inhibitor treatment in a context of haematological malignancies
* Being unable or unwilling to comply with the requirements of the protocol, as assessed by the investigator
* Patient in urgency situation, adult under legal protection, or unable to give his consent

Primary outcomes:
measure: Number of participants adverse events as assessed by CTCAE v5.0
timeFrame: From treatment initiation to 18 weeks after treatment initiation. (up to 24 months)
measure: European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (QLQ-C30) and Elderly Cancer Patients module (QLQ - ELD14), combined to compute a total score (between 44 and 128 points)
timeFrame: From inclusion until 24 weeks after treatment initiation (up to 24 months)
Secondary outcomes:
measure: geriatric data modifications under treatment
timeFrame: From inclusion until treatment discontinuation (up to 24 months)
measure: compare patients and clinician symptoms reporting
timeFrame: From treatment initiation to 18 weeks after treatment initiation.(up to 24 months)
measure: Progression-free survival
timeFrame: time from treatment beginning to radiological or clinical progression of the disease, or death of any cause. (up to 24 months)
measure: Overall Survival
timeFrame: time from treatment beginning to death of any cause (up to 24 months)
measure: correlation between toxicity and efficacy
timeFrame: time from treatment beginning to radiological or clinical progression of the disease, or death of any cause. (up to 24 months)
measure: rate of grade 3 to 5 adverse events 18 weeks after treatment initiation
timeFrame: From treatment initiation to 18 weeks after treatment initiation.(up to 24 months)
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique des Hôpitaux de Marseille
state: Bouches Du Rhône
city: Marseille
country: France
facility: Institut Paoli-Calmettes
state: Bouches-du Rhône
city: Bordeaux
country: France
facility: Institut BERGONIE
city: Caen
country: France
facility: CENTRE Francois Baclesse
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Montpellier
country: France
facility: Institut Du Cancer de Montpellier
city: Paris
country: France
facility: Institut Curie
city: Saint-Herblain
country: France
facility: Institut De Cancérologie de l'Ouest
city: Toulouse
country: France
facility: IUCT-Oncopole Institut Claudius Rigaud
Study officials:
affiliation: Institut Paoli-Calmettes
name: Renaud Sabatier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist. 2000;5(3):224-37. doi: 10.1634/theoncologist.5-3-224.
citation: Basch E, Iasonos A, McDonough T, Barz A, Culkin A, Kris MG, Scher HI, Schrag D. Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study. Lancet Oncol. 2006 Nov;7(11):903-9. doi: 10.1016/S1470-2045(06)70910-X.
citation: Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.
citation: Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.
citation: Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.
citation: Cella D, Grunwald V, Nathan P, Doan J, Dastani H, Taylor F, Bennett B, DeRosa M, Berry S, Broglio K, Berghorn E, Motzer RJ. Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimus in CheckMate 025: a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):994-1003. doi: 10.1016/S1470-2045(16)30125-5. Epub 2016 Jun 6.
citation: Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, Chaput N, Eggermont A, Marabelle A, Soria JC, Ferte C. Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1. Clin Cancer Res. 2017 Apr 15;23(8):1920-1928. doi: 10.1158/1078-0432.CCR-16-1741. Epub 2016 Nov 8.
citation: Daste A, Domblides C, Gross-Goupil M, Chakiba C, Quivy A, Cochin V, de Mones E, Larmonier N, Soubeyran P, Ravaud A. Immune checkpoint inhibitors and elderly people: A review. Eur J Cancer. 2017 Sep;82:155-166. doi: 10.1016/j.ejca.2017.05.044. Epub 2017 Jul 6.
citation: Du-Thanh A, Lesage C, Ferreira E, Dereure O, Guillot B. [Innovative therapies for metastatic melanoma in elderly patients]. Ann Dermatol Venereol. 2015 Oct;142(10):549-56. doi: 10.1016/j.annder.2015.03.022. Epub 2015 May 16. French.
citation: Extermann M. Measurement and impact of comorbidity in older cancer patients. Crit Rev Oncol Hematol. 2000 Sep;35(3):181-200. doi: 10.1016/s1040-8428(00)00090-1.
citation: Fitzsimmons D, Gilbert J, Howse F, Young T, Arrarras JI, Bredart A, Hawker S, George S, Aapro M, Johnson CD. A systematic review of the use and validation of health-related quality of life instruments in older cancer patients. Eur J Cancer. 2009 Jan;45(1):19-32. doi: 10.1016/j.ejca.2008.07.036. Epub 2008 Sep 25.
citation: Greenhalgh J. The applications of PROs in clinical practice: what are they, do they work, and why? Qual Life Res. 2009 Feb;18(1):115-23. doi: 10.1007/s11136-008-9430-6. Epub 2008 Dec 23.
citation: Helissey C, Vicier C, Champiat S. The development of immunotherapy in older adults: New treatments, new toxicities? J Geriatr Oncol. 2016 Sep;7(5):325-33. doi: 10.1016/j.jgo.2016.05.007. Epub 2016 Jun 16.
citation: Hjermstad MJ, Fayers PM, Bjordal K, Kaasa S. Using reference data on quality of life--the importance of adjusting for age and gender, exemplified by the EORTC QLQ-C30 (+3). Eur J Cancer. 1998 Aug;34(9):1381-9. doi: 10.1016/s0959-8049(98)00136-1.
citation: Hua C, Boussemart L, Mateus C, Routier E, Boutros C, Cazenave H, Viollet R, Thomas M, Roy S, Benannoune N, Tomasic G, Soria JC, Champiat S, Texier M, Lanoy E, Robert C. Association of Vitiligo With Tumor Response in Patients With Metastatic Melanoma Treated With Pembrolizumab. JAMA Dermatol. 2016 Jan;152(1):45-51. doi: 10.1001/jamadermatol.2015.2707.
citation: Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992 Nov;11(11):3887-95. doi: 10.1002/j.1460-2075.1992.tb05481.x.
citation: Khoja L, Day D, Wei-Wu Chen T, Siu LL, Hansen AR. Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review. Ann Oncol. 2017 Oct 1;28(10):2377-2385. doi: 10.1093/annonc/mdx286.
citation: Lafage-Pochitaloff M, Costello R, Couez D, Simonetti J, Mannoni P, Mawas C, Olive D. Human CD28 and CTLA-4 Ig superfamily genes are located on chromosome 2 at bands q33-q34. Immunogenetics. 1990;31(3):198-201. doi: 10.1007/BF00211556.
citation: Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Jul 2;373(1):23-34. doi: 10.1056/NEJMoa1504030. Epub 2015 May 31. Erratum In: N Engl J Med. 2018 Nov 29;379(22):2185. doi: 10.1056/NEJMx180040.
citation: Manoussakis MN, Tzioufas AG, Silis MP, Pange PJ, Goudevenos J, Moutsopoulos HM. High prevalence of anti-cardiolipin and other autoantibodies in a healthy elderly population. Clin Exp Immunol. 1987 Sep;69(3):557-65.
citation: Michelson H, Bolund C, Brandberg Y. Multiple chronic health problems are negatively associated with health related quality of life (HRQoL) irrespective of age. Qual Life Res. 2000;9(10):1093-104. doi: 10.1023/a:1016654621784.
citation: Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1803-13. doi: 10.1056/NEJMoa1510665. Epub 2015 Sep 25.
citation: Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, Postow MA, Wolchok JD. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015 Dec;26(12):2375-91. doi: 10.1093/annonc/mdv383. Epub 2015 Sep 14.
citation: Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL, Cheever MA. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. N Engl J Med. 2016 Jun 30;374(26):2542-52. doi: 10.1056/NEJMoa1603702. Epub 2016 Apr 19.
citation: Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. doi: 10.1056/NEJMoa1606774. Epub 2016 Oct 8.
citation: Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, De Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR; OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21;389(10066):255-265. doi: 10.1016/S0140-6736(16)32517-X. Epub 2016 Dec 13.
citation: Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, Chiarion-Sileni V, Drucis K, Krajsova I, Hauschild A, Lorigan P, Wolter P, Long GV, Flaherty K, Nathan P, Ribas A, Martin AM, Sun P, Crist W, Legos J, Rubin SD, Little SM, Schadendorf D. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015 Jan 1;372(1):30-9. doi: 10.1056/NEJMoa1412690. Epub 2014 Nov 16.
citation: Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011 Jun 30;364(26):2517-26. doi: 10.1056/NEJMoa1104621. Epub 2011 Jun 5.
citation: Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T. Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Semin Immunol. 2012 Oct;24(5):331-41. doi: 10.1016/j.smim.2012.04.008. Epub 2012 May 4.
citation: Wheelwright S, Darlington AS, Fitzsimmons D, Fayers P, Arraras JI, Bonnetain F, Brain E, Bredart A, Chie WC, Giesinger J, Hammerlid E, O'Connor SJ, Oerlemans S, Pallis A, Reed M, Singhal N, Vassiliou V, Young T, Johnson C. International validation of the EORTC QLQ-ELD14 questionnaire for assessment of health-related quality of life elderly patients with cancer. Br J Cancer. 2013 Aug 20;109(4):852-8. doi: 10.1038/bjc.2013.407. Epub 2013 Jul 18.
citation: Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146.
citation: Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991 Feb;39(2):142-8. doi: 10.1111/j.1532-5415.1991.tb01616.x.
citation: Bandeen-Roche K, Xue QL, Ferrucci L, Walston J, Guralnik JM, Chaves P, Zeger SL, Fried LP. Phenotype of frailty: characterization in the women's health and aging studies. J Gerontol A Biol Sci Med Sci. 2006 Mar;61(3):262-6. doi: 10.1093/gerona/61.3.262.
citation: Davis HS, MacPherson K, Merry HR, Wentzel C, Rockwood K. Reliability and validity of questions about exercise in the Canadian Study of Health and Aging. Int Psychogeriatr. 2001;13 Supp 1:177-82. doi: 10.1017/s1041610202008128.
citation: Cornali C, Franzoni S, Frisoni GB, Trabucchi M. Anorexia as an independent predictor of mortality. J Am Geriatr Soc. 2005 Feb;53(2):354-5. doi: 10.1111/j.1532-5415.2005.53126_4.x. No abstract available.
citation: Cheng ST, Chan AC. Comparative performance of long and short forms of the Geriatric Depression Scale in mildly demented Chinese. Int J Geriatr Psychiatry. 2005 Dec;20(12):1131-7. doi: 10.1002/gps.1405.
citation: Clement JP, Nassif RF, Leger JM, Marchan F. [Development and contribution to the validation of a brief French version of the Yesavage Geriatric Depression Scale]. Encephale. 1997 Mar-Apr;23(2):91-9. French.
citation: Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, Januel JM, Sundararajan V. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011 Mar 15;173(6):676-82. doi: 10.1093/aje/kwq433. Epub 2011 Feb 17.
citation: Borson S, Scanlan JM, Chen P, Ganguli M. The Mini-Cog as a screen for dementia: validation in a population-based sample. J Am Geriatr Soc. 2003 Oct;51(10):1451-4. doi: 10.1046/j.1532-5415.2003.51465.x.
citation: Borson S, Scanlan J, Brush M, Vitaliano P, Dokmak A. The mini-cog: a cognitive 'vital signs' measure for dementia screening in multi-lingual elderly. Int J Geriatr Psychiatry. 2000 Nov;15(11):1021-7. doi: 10.1002/1099-1166(200011)15:113.0.co;2-6.
citation: Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969 Autumn;9(3):179-86. No abstract available.
citation: Barberger-Gateau P, Dartigues JF, Letenneur L. Four Instrumental Activities of Daily Living Score as a predictor of one-year incident dementia. Age Ageing. 1993 Nov;22(6):457-63. doi: 10.1093/ageing/22.6.457.
citation: KATZ S, FORD AB, MOSKOWITZ RW, JACKSON BA, JAFFE MW. STUDIES OF ILLNESS IN THE AGED. THE INDEX OF ADL: A STANDARDIZED MEASURE OF BIOLOGICAL AND PSYCHOSOCIAL FUNCTION. JAMA. 1963 Sep 21;185:914-9. doi: 10.1001/jama.1963.03060120024016. No abstract available.