Clinical trial NCT01830153: RAD001 in Advanced Sarcoma
Official title: A Phase II Multicenter Trial of RAD001 in Patients With Metastatic or Recurrent Sarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Soft Tissue Sarcomas
Bone Sarcomas
Keywords: Soft tissue sarcomas
Bone sarcomas
RAD001
Refractory to conventional chemotherapy
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2013-04-12
Enrollment: 41
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial intends to test the efficacy and safety of RAD001 in patients with advanced sarcoma who failed to conventional chemotherapy.

Detailed description: This multicenter, phase II trial evaluated the efficacy and safety of everolimus in patients with metastatic or recurrent bone and soft tissue sarcoma after failure of anthracycline and/or ifosfamide.

Eligibility criteria: Inclusion Criteria:

* Patients with histologically confirmed metastatic, unresectable bone or soft tissue sarcomas who had past treatment with anthracycline and/or ifosfamide to which the disease was primarily refractory or progressed after initial response.
* Any of above drugs is allowed to be used as adjuvant treatment.
* Unidimensionally measurable disease
* 3 or less than prior chemotherapies
* Age 17 years old or older
* ECOG performance status 2 or less, Life expectancy 6 month or less
* Adequate bone marrow, liver, kidney, and cardiac function
* Written informed consent

Exclusion Criteria:

* Pregnant or lactating patients
* Patients with resectable metastasis
* Patients with history of CNS metastasis
* Gastrointestinal stromal tumors, chondrosarcoma, neuroblastoma
* Hypersensitivity to the active substance, to other rapamycin derivatives, or to any of the excipients.
* Any preexisting medical condition of sufficient severity to prevent full compliance with the study

Primary outcomes:
measure: Progression-free survival rate at 16 weeks
timeFrame: 16 weeks
Secondary outcomes:
measure: Progression-free survival
timeFrame: Up to 24 months
measure: Overall survival
timeFrame: Up to 24 months
measure: Response rate
timeFrame: Up to 24 months
measure: Toxicity
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, University of Ulsan College of Medicine
state: N/A = Not Applicable
city: Daegu
country: Korea, Republic of
facility: Yeongnam University College of Medicine
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei Cancer Center
city: Seoul
country: Korea, Republic of
facility: Korea University
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Asan Medical Center
name: Jin-Hee Ahn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Edmonson JH, Ryan LM, Blum RH, Brooks JS, Shiraki M, Frytak S, Parkinson DR. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993 Jul;11(7):1269-75. doi: 10.1200/JCO.1993.11.7.1269.
citation: Verweij J, Lee SM, Ruka W, Buesa J, Coleman R, van Hoessel R, Seynaeve C, di Paola ED, van Glabbeke M, Tonelli D, Judson IR. Randomized phase II study of docetaxel versus doxorubicin in first- and second-line chemotherapy for locally advanced or metastatic soft tissue sarcomas in adults: a study of the european organization for research and treatment of cancer soft tissue and bone sarcoma group. J Clin Oncol. 2000 May;18(10):2081-6. doi: 10.1200/JCO.2000.18.10.2081.
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citation: Santoro A, Tursz T, Mouridsen H, Verweij J, Steward W, Somers R, Buesa J, Casali P, Spooner D, Rankin E, et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1995 Jul;13(7):1537-45. doi: 10.1200/JCO.1995.13.7.1537.
citation: Le Cesne A, Judson I, Crowther D, Rodenhuis S, Keizer HJ, Van Hoesel Q, Blay JY, Frisch J, Van Glabbeke M, Hermans C, Van Oosterom A, Tursz T, Verweij J. Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: A trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 2000 Jul;18(14):2676-84. doi: 10.1200/JCO.2000.18.14.2676.
citation: van Oosterom AT, Mouridsen HT, Nielsen OS, Dombernowsky P, Krzemieniecki K, Judson I, Svancarova L, Spooner D, Hermans C, Van Glabbeke M, Verweij J; EORTC Soft Tissue and Bone Sarcoma Group. Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer. 2002 Dec;38(18):2397-406. doi: 10.1016/s0959-8049(02)00491-4.
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citation: Wan X, Helman LJ. The biology behind mTOR inhibition in sarcoma. Oncologist. 2007 Aug;12(8):1007-18. doi: 10.1634/theoncologist.12-8-1007.
citation: Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. doi: 10.1016/S0140-6736(08)61039-9. Epub 2008 Jul 22.
citation: Yoo C, Lee J, Rha SY, Park KH, Kim TM, Kim YJ, Lee HJ, Lee KH, Ahn JH. Multicenter phase II study of everolimus in patients with metastatic or recurrent bone and soft-tissue sarcomas after failure of anthracycline and ifosfamide. Invest New Drugs. 2013 Dec;31(6):1602-8. doi: 10.1007/s10637-013-0028-7. Epub 2013 Sep 14.