Lenalidomide Maintenance Therapy in Stage IIIB/IV Non-small Cell Lung Cancer

NCT02018523 | Terminated Phase 1 DMC

• 1 other identifier: H-32774
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the safety and efficacy of maintenance therapy with daily low dose lenalidomide in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) after first line chemotherapy. Investigators expect this treatment approach will delay disease progression by boosting the patient's anti-tumor immune response. Investigators hypothesize that 10 mg/day of lenalidomide can be administered safely as maintenance therapy and improve progression free survival time.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Carcinoma, Non-Small-Cell Lung; Stage 3B/4; Maintenance Therapy; Lenalidomide

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival is defined as the duration of time from the date starting lenalidomide to the date of documented radiographic progression or death.

  up to 6 months from the date of registration

Secondary Outcomes (7)

• Number of participants with adverse events

  From date of registration to end of study, up to 3 years

• Change in circulating immune cells

  Change from baseline at 1 week

• Change in circulating immune cells

  Change from baseline at 5 weeks

• Change in circulating immune cells

  Change from baseline at 9 weeks

• Change in circulating immune cells

  Change from baseline at 13, 17, 21 and 25 weeks

Study Arms (1)

Lenalidomide

EXPERIMENTAL

Oral lenalidomide 10 mg daily until disease progression

Drug: Lenalidomide

Interventions

Lenalidomide DRUG

lenalidomide 10mg/day orally until disease progression

Also known as: Revlimid

Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed stage IIIB or stage IV NSCLC with measurable disease at initial presentation prior to chemotherapy. See Section 8.4.1 for measurable disease parameters.
• Patients must have had a complete response (CR), partial response (PR) or stable disease (SD) after 4-6 cycles of first-line chemotherapy. Tumor response will be assessed by RECIST criteria version 1.1.
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, or radiotherapy before entering this study.
• Myelosuppressive chemotherapy: At least 21 days elapsed from end of treatment before registration (42 days if prior nitrosourea).
• Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor.
• Other: For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
• XRT: \> or = to 2 weeks for local palliative XRT (small port); 3 months must have elapsed if 50% radiation of pelvis; 6 weeks must have elapsed if other substantial bone marrow radiation.
• Patients must be \> or = 18 years of age.
• ECOG performance status \< or = to 1 (Karnofsky \> 70%).
• Organ Functions: Patients must have normal organ and marrow function as defined below within 28 days of registration:
• Leukocytes \> or = 3,000/uL
• Absolute neutrophil count \> or = 1,500/uL
• Hemoglobin \> or = 8 g/dL
• Platelets \> or = 100,000/uL
• Total bilirubin 1.5X institutional upper limit of normal (ULN)

You may not qualify if:

• Concomitant Medications:
• Patients may not be receiving any other anti-cancer therapy.
• Patients may not be receiving any other investigational agents.
• Patients may not be receiving systemic steroids or other immunosuppressive drugs; however, steroid containing inhaler may be allowed after discussing with the Principal Investigator. Duration of 5 half-lives must have elapsed before the study registration if the patient was on systemic steroids or other immunosuppressive drugs.
• Patients with untreated brain metastasis, or with treated brain metastasis but requiring steroids.
• Patients with known EGFR mutation or EML-ALK fusion gene and with stage IV disease.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide or thalidomide.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia, autoimmune disease or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study because lenalidomide has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide.
• Known sera-positive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
• Any other clinically significant medical condition and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol or which, in the views of investigator, preclude combination chemotherapy.

Sponsors & Collaborators

• Jun Zhang: lead
• Celgene Corporation: collaborator
• Baylor College of Medicine: collaborator

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (27)

• Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. doi: 10.1056/NEJMoa011954.

  PMID: 11784875 BACKGROUND

• Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, Esteban E, Molinier O, Brugger W, Melezinek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010 Jun;11(6):521-9. doi: 10.1016/S1470-2045(10)70112-1. Epub 2010 May 20.

  PMID: 20493771 BACKGROUND

• Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. doi: 10.1200/JCO.2012.47.1102. Epub 2013 Jul 8.

  PMID: 23835707 BACKGROUND

• Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu YL, Bover I, Begbie S, Tzekova V, Cucevic B, Pereira JR, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009 Oct 24;374(9699):1432-40. doi: 10.1016/S0140-6736(09)61497-5. Epub 2009 Sep 18.

  PMID: 19767093 BACKGROUND

• Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008 May 30;133(5):775-87. doi: 10.1016/j.cell.2008.05.009.

  PMID: 18510923 BACKGROUND

• Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund LT. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res. 2008 Aug 15;14(16):5220-7. doi: 10.1158/1078-0432.CCR-08-0133.

  PMID: 18698040 BACKGROUND

• Kawai O, Ishii G, Kubota K, Murata Y, Naito Y, Mizuno T, Aokage K, Saijo N, Nishiwaki Y, Gemma A, Kudoh S, Ochiai A. Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer. 2008 Sep 15;113(6):1387-95. doi: 10.1002/cncr.23712.

  PMID: 18671239 BACKGROUND

• Petersen RP, Campa MJ, Sperlazza J, Conlon D, Joshi MB, Harpole DH Jr, Patz EF Jr. Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer. 2006 Dec 15;107(12):2866-72. doi: 10.1002/cncr.22282.

  PMID: 17099880 BACKGROUND

• Shimizu K, Nakata M, Hirami Y, Yukawa T, Maeda A, Tanemoto K. Tumor-infiltrating Foxp3+ regulatory T cells are correlated with cyclooxygenase-2 expression and are associated with recurrence in resected non-small cell lung cancer. J Thorac Oncol. 2010 May;5(5):585-90. doi: 10.1097/JTO.0b013e3181d60fd7.

  PMID: 20234320 BACKGROUND

• Erfani N, Mehrabadi SM, Ghayumi MA, Haghshenas MR, Mojtahedi Z, Ghaderi A, Amani D. Increase of regulatory T cells in metastatic stage and CTLA-4 over expression in lymphocytes of patients with non-small cell lung cancer (NSCLC). Lung Cancer. 2012 Aug;77(2):306-11. doi: 10.1016/j.lungcan.2012.04.011. Epub 2012 May 17.

  PMID: 22608141 BACKGROUND

• Karagoz B, Bilgi O, Gumus M, Erikci AA, Sayan O, Turken O, Kandemir EG, Ozturk A, Yaylaci M. CD8+CD28- cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients. Med Oncol. 2010 Mar;27(1):29-33. doi: 10.1007/s12032-008-9165-9. Epub 2009 Jan 16.

  PMID: 19148592 BACKGROUND

• Elias D, Lasser PH, Desruennes E, Mankarios H, Jiang Y. Surgical approach to segment I for malignant tumors of the liver. Surg Gynecol Obstet. 1992 Jul;175(1):17-24.

  PMID: 1621195 BACKGROUND

• Okita R, Saeki T, Takashima S, Yamaguchi Y, Toge T. CD4+CD25+ regulatory T cells in the peripheral blood of patients with breast cancer and non-small cell lung cancer. Oncol Rep. 2005 Nov;14(5):1269-73.

  PMID: 16211295 BACKGROUND

• Woo EY, Yeh H, Chu CS, Schlienger K, Carroll RG, Riley JL, Kaiser LR, June CH. Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol. 2002 May 1;168(9):4272-6. doi: 10.4049/jimmunol.168.9.4272.

  PMID: 11970966 BACKGROUND

• LeBlanc R, Hideshima T, Catley LP, Shringarpure R, Burger R, Mitsiades N, Mitsiades C, Cheema P, Chauhan D, Richardson PG, Anderson KC, Munshi NC. Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood. 2004 Mar 1;103(5):1787-90. doi: 10.1182/blood-2003-02-0361. Epub 2003 Sep 25.

  PMID: 14512311 BACKGROUND

• Chang DH, Liu N, Klimek V, Hassoun H, Mazumder A, Nimer SD, Jagannath S, Dhodapkar MV. Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood. 2006 Jul 15;108(2):618-21. doi: 10.1182/blood-2005-10-4184. Epub 2006 Mar 28.

  PMID: 16569772 BACKGROUND

• Galustian C, Meyer B, Labarthe MC, Dredge K, Klaschka D, Henry J, Todryk S, Chen R, Muller G, Stirling D, Schafer P, Bartlett JB, Dalgleish AG. The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother. 2009 Jul;58(7):1033-45. doi: 10.1007/s00262-008-0620-4. Epub 2008 Nov 14.

  PMID: 19009291 BACKGROUND

• Lu L, Payvandi F, Wu L, Zhang LH, Hariri RJ, Man HW, Chen RS, Muller GW, Hughes CC, Stirling DI, Schafer PH, Bartlett JB. The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions. Microvasc Res. 2009 Mar;77(2):78-86. doi: 10.1016/j.mvr.2008.08.003. Epub 2008 Sep 4.

  PMID: 18805433 BACKGROUND

• Dredge K, Horsfall R, Robinson SP, Zhang LH, Lu L, Tang Y, Shirley MA, Muller G, Schafer P, Stirling D, Dalgleish AG, Bartlett JB. Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc Res. 2005 Jan;69(1-2):56-63. doi: 10.1016/j.mvr.2005.01.002.

  PMID: 15797261 BACKGROUND

• Eisen T, Trefzer U, Hamilton A, Hersey P, Millward M, Knight RD, Jungnelius JU, Glaspy J. Results of a multicenter, randomized, double-blind phase 2/3 study of lenalidomide in the treatment of pretreated relapsed or refractory metastatic malignant melanoma. Cancer. 2010 Jan 1;116(1):146-54. doi: 10.1002/cncr.24686.

  PMID: 19862820 BACKGROUND

• Miller AA, Case D, Harmon M, Savage P, Lesser G, Hurd D, Melin SA. Phase I study of lenalidomide in solid tumors. J Thorac Oncol. 2007 May;2(5):445-9. doi: 10.1097/01.JTO.0000268679.33238.67.

  PMID: 17473661 BACKGROUND

• Dahut WL, Aragon-Ching JB, Woo S, Tohnya TM, Gulley JL, Arlen PM, Wright JJ, Ventiz J, Figg WD. Phase I study of oral lenalidomide in patients with refractory metastatic cancer. J Clin Pharmacol. 2009 Jun;49(6):650-60. doi: 10.1177/0091270009335001.

  PMID: 19451403 BACKGROUND

• Bartlett JB, Michael A, Clarke IA, Dredge K, Nicholson S, Kristeleit H, Polychronis A, Pandha H, Muller GW, Stirling DI, Zeldis J, Dalgleish AG. Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. Br J Cancer. 2004 Mar 8;90(5):955-61. doi: 10.1038/sj.bjc.6601579.

  PMID: 14997189 BACKGROUND

• Sanborn SL, Gibbons J, Krishnamurthi S, Brell JM, Dowlati A, Bokar JA, Nock C, Horvath N, Bako J, Remick SC, Cooney MM. Phase I trial of docetaxel given every 3 weeks and daily lenalidomide in patients with advanced solid tumors. Invest New Drugs. 2009 Oct;27(5):453-60. doi: 10.1007/s10637-008-9200-x. Epub 2008 Nov 15.

  PMID: 19011760 BACKGROUND

• Kalmadi S, Davis M, Dowlati A, O'Keefe S, Cline-Burkhardt M, Pelley RJ, Borden E, Dreicer R, Bukowski R, Mekhail T. Phase I trial of three-weekly docetaxel, carboplatin and oral lenalidomide (Revlimid) in patients with advanced solid tumors. Invest New Drugs. 2007 Jun;25(3):211-6. doi: 10.1007/s10637-006-9025-4. Epub 2006 Nov 11.

  PMID: 17103043 BACKGROUND

• Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL; IFM Investigators. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1782-91. doi: 10.1056/NEJMoa1114138.

  PMID: 22571202 BACKGROUND

• McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1770-81. doi: 10.1056/NEJMoa1114083.

  PMID: 22571201 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jun Zhang, M.D.

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 17, 2013
• First Posted: December 23, 2013
• Study Start: June 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: January 18, 2018

Record last verified: 2018-01

Locations

US (1)