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Trial record 6 of 13 for:    Recruiting, Not yet recruiting, Available Studies | "Urethral Neoplasms"

Four Cycles Versus Six Cycles of Cisplatin-based Chemotherapy in Metastatic Urothelial Carcinoma (FOCUS)

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ClinicalTrials.gov Identifier: NCT03296306
Recruitment Status : Recruiting
First Posted : September 28, 2017
Last Update Posted : September 28, 2017
Sponsor:
Collaborator:
Korean Cancer Study Group
Information provided by (Responsible Party):
Jae-Lyun Lee, Asan Medical Center

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.

Condition or disease Intervention/treatment Phase
Bladder Cancer Ureter Cancer Urethral Cancer Transitional Cell Carcinoma Drug: Treatment duration of cisplatin based chemotherapy Phase 3

Detailed Description:

Urothelial carcinoma is the fifth most common cancer in men and seventh among women all around the world. Although a complete surgical resection with or without perioperative treatment is the most effective way to offer a potentially curative therapy to patients with these cancers, 25% of the patients initially present with locally or systemically advanced disease. Systemic chemotherapy is the only current modality that provides the potential for a long-term survival in patients with advanced or metastatic urothelial disease.

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Four Cycles of Cisplatin-Based Chemotherapy in Metastatic Urothelial Carcinoma Compared to Six Cycles: Randomized Phase III Trial - FOCUS Study -
Study Start Date : September 2016
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : February 2022


Arm Intervention/treatment
Active Comparator: 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)
Drug: 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

Experimental: 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)
Drug: 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




Primary Outcome Measures :
  1. Overall survival [ Time Frame: 5 years ]
    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)


Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: Every 6-8 weeks, from date of enrollment until the date of first documented progression ]
    PFS is defined as the time from enrollment of study until either first documentation of RECIST-defined disease progression or death due to any cause, whichever come first.

  2. Tumor response rate [ Time Frame: Every 6-8 weeks, assess the tumor response from date of enrollment ]
    Tumor response rate is defined as the proportion of patients with a complete response (CR) or partial response (PR) among patients with evaluable lesions for response of RECIST.

  3. safety using NCI Common Terminology Criteria for Adverse Events (version 4.03) [ Time Frame: Every 2-4 weeks, from date of enrollment until 30th days of last cycles treatment or initation of new regimen ]
    Toxicity profiles will be evaluated every cycle with physical examination, vital signs, performance status, CBC, and serum chemistry using NCI Common Terminology Criteria for Adverse Events version 4.03.

  4. Quality of life composite score of EORTC-QoL-C30 and EORTC CIPN20 [ Time Frame: 0-1 week, 12-18 week, 24-34 week after enrollment ]
    Investigators measured Quality of life using EORTC-QoL-C30 and EORTC CIPN20 at the time of enrollment, 12-18 weeks, and 30 weeks



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Patients with histologically or cytologically confirmed urothelial cancer
  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:

  1. Histologic types other than urothelial cell carcinoma should be excluded. However, urothelial cell types combined with squamous or glandular features are allowed.
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03296306


Contacts
Contact: Jae lyun Lee, MD., PhD. +82-2-3010-5977 jaelyun@amc.seoul.kr
Contact: MiRan Kim +82-2-3010-5576 crnonc12@amc.seoul.kr

Locations
Korea, Republic of
Kwonoh Park Recruiting
Yangsan, Gyeongsangnam-do, Korea, Republic of, 50612
Contact: Kwonoh Park, MD, PhD    1033783529    parkkoh@daum.net   
Hallym University Medical Center, Hallym University College of Medicine Recruiting
Anyang, Korea, Republic of
Contact: Ho Young Kim       ksfam@daum.net   
Fatima Hospital Recruiting
Daegu, Korea, Republic of
Contact: Jung Lim Lee       junglim3@gmail.com   
Keimyeong University Dongsan Medical Center Recruiting
Daegu, Korea, Republic of
Contact: Jin Young Kim, MD       takgu@dsmc.or.kr   
Chungnam University Hospital Recruiting
Daejeon, Korea, Republic of
Contact: Hyo Jin Lee, MD, PhD.       cymed@cnu.ac.kr   
National Health Insurance Service Ilsan Hospital Recruiting
Goyang, Korea, Republic of
Contact: Soo Jung Hong       suzzy901@nhimc.or.kr   
Gil Medical Center Recruiting
Incheon, Korea, Republic of
Contact: Inkeun Park, MD, PhD       ingni79@hanmail.net   
Inje University Haeundae Paik Hospital Recruiting
Pusan, Korea, Republic of
Contact: Il-Hwan Kim       onelement@daum.net   
Kosin University Hospital Recruiting
Pusan, Korea, Republic of
Contact: Sung-Hoon Shin       ssh1533@daum.net   
Pusan National University Hospital, Pusan National University School of Medicine Recruiting
Pusan, Korea, Republic of
Contact: Hyo Jung Kim       leonkim80@naver.com   
Asan Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Jae-Lyun Lee, MD, PhD       jaelyun@amc.seoul.kr   
Chung Ang University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Hee Joon Kim         
Inje University Sanggye Paik Hospital Recruiting
Seoul, Korea, Republic of
Contact: Byeong Seok Sohn       imbs@paik.ac.kr   
Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine Recruiting
Seoul, Korea, Republic of
Contact: Yun-Gyoo Lee       gosciny@gmail.com   
Korea University Anam Hospital Recruiting
Seoul, Korea, Republic of
Contact: Yoon Ji Choi       yoonji23@hanmail.net   
Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine Recruiting
Seoul, Korea, Republic of
Contact: Bhum Suk Keam         
Contact       bhumsuk@snu.ac.kr   
VHS medical center Recruiting
Seoul, Korea, Republic of
Contact: Bong-Seog Kim         
Yonsei Cancer Center Recruiting
Seoul, Korea, Republic of
Contact: Sang Joon Shin       ssj338@yuhs.ac   
St. Vincent's Hospital, The Catholic University of Korea Recruiting
Suwon, Korea, Republic of
Contact: Byoung Yong Shim       shimby@catholic.ac.kr   
Sponsors and Collaborators
Asan Medical Center
Korean Cancer Study Group
Investigators
Principal Investigator: Jae-Lyun Lee, MD., PhD. Asan Medical Center

Publications of Results:

Responsible Party: Jae-Lyun Lee, Associated Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT03296306     History of Changes
Other Study ID Numbers: KCSG GU16-02
First Posted: September 28, 2017    Key Record Dates
Last Update Posted: September 28, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jae-Lyun Lee, Asan Medical Center:
urothelial carcinoma
cisplatin
first-line chemotherapy

Additional relevant MeSH terms:
Urethral Neoplasms
Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Ureteral Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Ureteral Diseases
Cisplatin
Antineoplastic Agents