NCT03296306

Brief Summary

The objective is to show non-inferiority of overall survival between four cycles and six cycles of first-line cisplatin based chemotherapy to determine the optimal duration of chemotherapy in patients with advanced urothelial carcinoma.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
330

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Sep 2016

Longer than P75 for phase_3

Geographic Reach
1 country

19 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 22, 2016

Completed
10 days until next milestone

Study Start

First participant enrolled

September 1, 2016

Completed
1.1 years until next milestone

First Posted

Study publicly available on registry

September 28, 2017

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2021

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2022

Completed
Last Updated

September 28, 2017

Status Verified

September 1, 2017

Enrollment Period

4.9 years

First QC Date

August 22, 2016

Last Update Submit

September 23, 2017

Conditions

Bladder CancerUreter CancerUrethral CancerTransitional Cell Carcinoma

Keywords

urothelial carcinomacisplatinfirst-line chemotherapy

Outcome Measures

Primary Outcomes (1)

  • Overall survival

    Overall survival is defined as the time from enrollment of study until death from any cause (or date of last follow-up for patients still alive)

    5 years

Secondary Outcomes (4)

  • Progression free survival

    Every 6-8 weeks, from date of enrollment until the date of first documented progression

  • Tumor response rate

    Every 6-8 weeks, assess the tumor response from date of enrollment

  • safety using NCI Common Terminology Criteria for Adverse Events (version 4.03)

    Every 2-4 weeks, from date of enrollment until 30th days of last cycles treatment or initation of new regimen

  • Quality of life composite score of EORTC-QoL-C30 and EORTC CIPN20

    0-1 week, 12-18 week, 24-34 week after enrollment

Study Arms (2)

6 cycles arm

ACTIVE COMPARATOR

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)

Drug: Treatment duration of cisplatin based chemotherapy

4 cycles arm

EXPERIMENTAL

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)

Drug: Treatment duration of cisplatin based chemotherapy

Interventions

Treatment duration of cisplatin based chemotherapyDRUG

* 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 arm6 cycles arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with histologically or cytologically confirmed urothelial cancer
  • Unresectable locally advanced (T3b, N2-3), metastatic (M1), or recurrent disease
  • Age 18 years or older
  • Eastern Cooperative Oncology Group performance status 0-1
  • Not progressed disease status after 2 or 4 cycles of platinum-based chemotherapy
  • Adequate organ and bone marrow function for chemotherapy
  • 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.
  • 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.
  • Patients should sign a written informed consent before study entry.

You may not qualify if:

  • Histologic types other than urothelial cell carcinoma should be excluded. However, urothelial cell types combined with squamous or glandular features are allowed.
  • 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%
  • Presence or history of CNS metastasis
  • 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)
  • Peripheral sensory neuropathy grade 2 or worse according to NCI CTCAE
  • History of treatment with drugs of another clinical trial within 30 days before enrollment.
  • 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
  • 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).
  • Pregnant or lactating women, women of childbearing potential not employing adequate contraception

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

Kwonoh Park

Yangsan, Gyeongsangnam-do, 50612, South Korea

RECRUITING

Hallym University Medical Center, Hallym University College of Medicine

Anyang, South Korea

RECRUITING

Fatima Hospital

Daegu, South Korea

RECRUITING

Keimyeong University Dongsan Medical Center

Daegu, South Korea

RECRUITING

Chungnam University Hospital

Daejeon, South Korea

RECRUITING

National Health Insurance Service Ilsan Hospital

Goyang, South Korea

RECRUITING

Gil Medical Center

Incheon, South Korea

RECRUITING

Inje University Haeundae Paik Hospital

Pusan, South Korea

RECRUITING

Kosin University Hospital

Pusan, South Korea

RECRUITING

Pusan National University Hospital, Pusan National University School of Medicine

Pusan, South Korea

RECRUITING

Asan Medical Center

Seoul, South Korea

RECRUITING

Chung Ang University Hospital

Seoul, South Korea

RECRUITING

Inje University Sanggye Paik Hospital

Seoul, South Korea

RECRUITING

Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine

Seoul, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, South Korea

RECRUITING

Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine

Seoul, South Korea

RECRUITING

VHS medical center

Seoul, South Korea

RECRUITING

Yonsei Cancer Center

Seoul, South Korea

RECRUITING

St. Vincent's Hospital, The Catholic University of Korea

Suwon, South Korea

RECRUITING

Related Publications (6)

  • 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.

    PMID: 18685414RESULT

  • 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.

    PMID: 11001674RESULT

  • 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.

    PMID: 16330205RESULT

  • 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.

    PMID: 1607913RESULT

  • 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.

    PMID: 26001531RESULT

  • 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.

    PMID: 18024869RESULT

MeSH Terms

Conditions

Urinary Bladder NeoplasmsUreteral NeoplasmsUrethral NeoplasmsCarcinoma, Transitional Cell

Condition Hierarchy (Ancestors)

Urologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteNeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital DiseasesUreteral DiseasesUrethral DiseasesCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Study Officials

  • Jae-Lyun Lee, MD., PhD.

    Asan Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jae lyun Lee, MD., PhD.

CONTACT

+82-2-3010-5977jaelyun@amc.seoul.kr

MiRan Kim

CONTACT

+82-2-3010-5576crnonc12@amc.seoul.kr

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associated Professor

Study Record Dates

First Submitted

August 22, 2016

First Posted

September 28, 2017

Study Start

September 1, 2016

Primary Completion

August 1, 2021

Study Completion

February 1, 2022

Last Updated

September 28, 2017

Record last verified: 2017-09

Locations

KR(19)