Four Cycles Versus Six Cycles of Cisplatin-based Chemotherapy in Metastatic Urothelial Carcinoma
NCT ID: NCT03296306
Last Updated: 2017-09-28
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
330 participants
INTERVENTIONAL
2016-09-30
2022-02-28
Brief Summary
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Detailed Description
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Cisplatin based combination chemotherapies such as GP, GP-S, MVAC, and dose dense MVAC with G-CSF supports are regarded as a backbone treatment for patients with advanced bladder cancer on the basis of the results from previous studies.
However, there is no consensus on appropriate number of chemotherapy cycles. In phase III trial comparing MVAC with GP, patients were treated with 6 cycles (every 4 weeks) of chemotherapy. In another phase III trial comparing MVAC with HD-MVAC, there is no pre-determined number of cycles, but the median number of cycles were 4 for MVAC and 6 for HD-MVAC.
However, it is hard to complete six or more cycles of cisplatin based chemotherapy due to cumulative toxicities of cisplatin such as neuropathy and development of resistance. The median age of patients with urothelial cancer is 70 years old and significant proportion of the patients already showed impaired performance status (ECOG PS ≥2).
There has already been reported in several trials of NSCLC, which showed that 4 cycles of chemotherapy containing cisplatin has no significant differences in survival or QoL with lower incidences of toxicities compared with 6 cycles of chemotherapy.
The objective of this trial is to assess whether there is any difference in OS between patients who are treated with four cycles of cisplatin based chemotherapy and patients who are treated with 6 cycles of chemotherapy to determine the optimal duration of chemotherapy in patients with advanced urothelial cancer.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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6 cycles arm
Patients without evidence of disease progression or unacceptable toxicities after completion of two or four treatment cycles of cisplatin based chemotherapy (GP, GP-S, MVAC, HD-MVAC with GCSF) were randomly assigned to receive additional two to four cycles of chemotherapy (totally six cycles)
Treatment duration of cisplatin based chemotherapy
* GP regimen: Gemcitabine (1000 mg/m2 D1, D8), Cisplatin (60 mg/m2 D1), every 3 weeks
* GP-S regimen: Gemcitabine (1000 mg/m2 D1, D8), Cisplatin (35 mg/m2 D1,D 2 or D8), every 3 weeks
* MVAC regimen: Methotrexate (30 mg/m2 IV bolus, D1, 15, 22), Vinblastine (3 mg/m2 IV bolus, D2, 15, 22), Doxorubicin (30 mg/m2 IV bolus D2), Cisplatin (70 mg/m2 D2), every 4 weeks
* HD-MVAC with GCSF regimen: Methotrexate (30 mg/m2 IV bolus, D1), Vinblastine (3 mg/m2 IV bolus, D2), Doxorubicin (30 mg/m2 IV bolus D2), Cisplatin (70 mg/m2 D2), G-CSF (240 ug/m2 SC, D4-10), every 2 weeks
4 cycles arm
Patients without evidence of disease progression or unacceptable toxicities after completion of two or four treatment cycles of cisplatin based chemotherapy (GP, GP-S, MVAC, HD-MVAC with GCSF) were randomly assigned to receive additional zero to two cycles of chemotherapy (totally four cycles)
Treatment duration of cisplatin based chemotherapy
* GP regimen: Gemcitabine (1000 mg/m2 D1, D8), Cisplatin (60 mg/m2 D1), every 3 weeks
* GP-S regimen: Gemcitabine (1000 mg/m2 D1, D8), Cisplatin (35 mg/m2 D1,D 2 or D8), every 3 weeks
* MVAC regimen: Methotrexate (30 mg/m2 IV bolus, D1, 15, 22), Vinblastine (3 mg/m2 IV bolus, D2, 15, 22), Doxorubicin (30 mg/m2 IV bolus D2), Cisplatin (70 mg/m2 D2), every 4 weeks
* HD-MVAC with GCSF regimen: Methotrexate (30 mg/m2 IV bolus, D1), Vinblastine (3 mg/m2 IV bolus, D2), Doxorubicin (30 mg/m2 IV bolus D2), Cisplatin (70 mg/m2 D2), G-CSF (240 ug/m2 SC, D4-10), every 2 weeks
Interventions
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Treatment duration of cisplatin based chemotherapy
* GP regimen: Gemcitabine (1000 mg/m2 D1, D8), Cisplatin (60 mg/m2 D1), every 3 weeks
* GP-S regimen: Gemcitabine (1000 mg/m2 D1, D8), Cisplatin (35 mg/m2 D1,D 2 or D8), every 3 weeks
* MVAC regimen: Methotrexate (30 mg/m2 IV bolus, D1, 15, 22), Vinblastine (3 mg/m2 IV bolus, D2, 15, 22), Doxorubicin (30 mg/m2 IV bolus D2), Cisplatin (70 mg/m2 D2), every 4 weeks
* HD-MVAC with GCSF regimen: Methotrexate (30 mg/m2 IV bolus, D1), Vinblastine (3 mg/m2 IV bolus, D2), Doxorubicin (30 mg/m2 IV bolus D2), Cisplatin (70 mg/m2 D2), G-CSF (240 ug/m2 SC, D4-10), every 2 weeks
Eligibility Criteria
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Inclusion Criteria
2. Unresectable locally advanced (T3b, N2-3), metastatic (M1), or recurrent disease
3. Age 18 years or older
4. Eastern Cooperative Oncology Group performance status 0-1
5. Not progressed disease status after 2 or 4 cycles of platinum-based chemotherapy
6. Adequate organ and bone marrow function for chemotherapy
7. No history of radiation therapy, or radiation field within 25% of whole marrow would be allowed. If patients underwent radiation therapy in entire pelvis, they are excluded to this study. Patients should discontinue radiation therapy at least 4 weeks before enrollment, and the patients should be recovered from radiation therapy associated adverse events.
8. Women should use contraceptive medication for 6 months after the end of the study or she would be post-menopause status. Men should consent with the contraception for 6 months after the end of the study or he would be infertile.
9. Patients should sign a written informed consent before study entry.
Exclusion Criteria
2. Patients who showed progressed disease status after 2 or 4 cycles of platinum-based chemotherapy, cannot be treated with additional chemotherapy due to adverse events, or already undertook with reduced dose of more than 50%
3. Presence or history of CNS metastasis
4. Prior systemic chemotherapy (But prior intravesical chemotherapy or immunotherapy was allowed, and recurrent disease after adjuvant or neoadjuvant cisplatin-based systemic chemotherapy is allowed if the last chemotherapy was administered 1 year or more before the patient enrollment)
5. Peripheral sensory neuropathy grade 2 or worse according to NCI CTCAE
6. History of treatment with drugs of another clinical trial within 30 days before enrollment.
7. Concomitant severe medical, surgical, or psychiatric disease or problems which can affect the results of the clinical trial or have possibilities of unexpected medical problems caused be the drug of clinical trial
8. History of another malignancy (but treated malignancy at least two years before enrollment were allowed, and cured non-melanoma skin cancer, any cured in-situ carcinoma, clinically insignificant localized prostate cancer, or papillary thyroid carcinoma are allowed even diagnosed less than 2 years before enrollment).
9. Pregnant or lactating women, women of childbearing potential not employing adequate contraception
18 Years
ALL
No
Sponsors
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Korean Cancer Study Group
OTHER
Asan Medical Center
OTHER
Responsible Party
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Jae-Lyun Lee
Associated Professor
Principal Investigators
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Jae-Lyun Lee, MD., PhD.
Role: PRINCIPAL_INVESTIGATOR
Asan Medical Center
Locations
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Kwonoh Park
Yangsan, Gyeongsangnam-do, South Korea
Hallym University Medical Center, Hallym University College of Medicine
Anyang, , South Korea
Fatima Hospital
Daegu, , South Korea
Keimyeong University Dongsan Medical Center
Daegu, , South Korea
Chungnam University Hospital
Daejeon, , South Korea
National Health Insurance Service Ilsan Hospital
Goyang, , South Korea
Gil Medical Center
Incheon, , South Korea
Inje University Haeundae Paik Hospital
Pusan, , South Korea
Kosin University Hospital
Pusan, , South Korea
Pusan National University Hospital, Pusan National University School of Medicine
Pusan, , South Korea
Asan Medical Center
Seoul, , South Korea
Chung Ang University Hospital
Seoul, , South Korea
Inje University Sanggye Paik Hospital
Seoul, , South Korea
Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
Seoul, , South Korea
Korea University Anam Hospital
Seoul, , South Korea
Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine
Seoul, , South Korea
VHS medical center
Seoul, , South Korea
Yonsei Cancer Center
Seoul, , South Korea
St. Vincent's Hospital, The Catholic University of Korea
Suwon, , South Korea
Countries
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Central Contacts
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Facility Contacts
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Hee Joon Kim
Role: primary
Bhum Suk Keam
Role: primary
Role: backup
Bong-Seog Kim
Role: primary
References
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Cheng T. Systemic therapy for unresectable and metastatic transitional cell carcinoma of the urothelium: first-line and beyond. Curr Opin Support Palliat Care. 2008 Sep;2(3):153-60. doi: 10.1097/SPC.0b013e328309c72c.
von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. doi: 10.1200/JCO.2000.18.17.3068.
Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, Witjes JA, Spina M, van Groeningen CJ, Duclos B, Roberts JT, de Balincourt C, Collette L; EORTC Genito-Urinary Cancer Group. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006 Jan;42(1):50-4. doi: 10.1016/j.ejca.2005.08.032. Epub 2005 Dec 5.
Loehrer PJ Sr, Einhorn LH, Elson PJ, Crawford ED, Kuebler P, Tannock I, Raghavan D, Stuart-Harris R, Sarosdy MF, Lowe BA, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992 Jul;10(7):1066-73. doi: 10.1200/JCO.1992.10.7.1066.
Kim YR, Lee JL, You D, Jeong IG, Song C, Hong B, Hong JH, Ahn H. Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma. Cancer Chemother Pharmacol. 2015 Jul;76(1):141-53. doi: 10.1007/s00280-015-2774-z. Epub 2015 May 23.
Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. doi: 10.1200/JCO.2007.10.8134.
Other Identifiers
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KCSG GU16-02
Identifier Type: -
Identifier Source: org_study_id