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Neoadjuvant Dose Dense MVAC in MIBC and Locally Advanced Urothelial Carcinoma

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ClinicalTrials.gov Identifier: NCT04047693
Recruitment Status : Recruiting
First Posted : August 7, 2019
Last Update Posted : August 25, 2020
Sponsor:
Information provided by (Responsible Party):
Kwonoh Park, MD phD, Pusan National University Yangsan Hospital

Brief Summary:
The objective is to investigate the efficacy and safety of four cycles of ddMVAC with G-CSF support in patients with MIBC and locally advanced UC

Condition or disease Intervention/treatment Phase
Muscle Invasive Bladder Cancer Urothelial Carcinoma Neoadjuvant Chemotherapy Drug: dose dense MVAC with pegylated GCSF Phase 2

Detailed Description:
  • Currently, most treatment guidelines including NCCN recommend a neoadjuvant chemotherapy (NAC) as a standard of care in muscle invasive bladder cancer (MIBC).
  • Although standard NAC regimen is controversial due to rare of head to head study between each regimens, cisplatin based multidrug combination regimens such as MVAC, GP, and dose dense MVAC (ddMVAC) with G-CSF supports are regarded as a backbone treatment on the basis of the results from previous studies.
  • Application of NAC is still relatively slow adoption in real practice. These slow adoption result from intuitive concerns such as significant toxicity of multidrug combination chemotherapy represented by MVAC and delayed application of radical surgical treatment in non-responder
  • The ddMVAC with G-CSF support regimen showed an improved efficacy compared with GP regimen, and tolerable compared with standard MVAC using application of routine G-CSF support and high intensity of cisplatin.
  • In case of clinically lymph node evolvement (cN+) is not for strict NAC, but patient with cN+ UC have been treated induction chemotherapy of similar NAC regimens and surgical treatment. So, this study included MIBC plus cN+ UC as locally advanced UC.
  • In Korea, there is a low adoption of NAC, additionally rare of ddMVAC with G-CFS in locally advanced UC. It is supposed concerns related with toxicity of ddMVAC. Although the concern is likely not true considering the previous result of the Western, there has not been studied ddMVAC as NAC in Asian including Korean.
  • The objective of this trial is to assess the efficacy and safety of four cycles of ddMVAC with G-CSF support in patients with locally advanced UC.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Prospective, Single institution, Open-label, Phase 2
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Neoadjuvant Chemotherapy With Dose Dense MVAC Followed by Radical Surgery in Patients With MIBC and Locally Advanced Urothelial Carcinoma of Bladder: Phase II, Single-arm Study
Actual Study Start Date : May 1, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ddMVAC
4 cycles of neoadjuvant chemotherapy using dose dense MVAC with G-CSF
Drug: dose dense MVAC with pegylated GCSF
Methotrexate, 30 mg/m2 IV bolus, Day 1 Vinblastine, 3 mg/m2 IV bolus, Day2 Doxorubicin, 30 mg/m2 IV bolus, Day2 Cisplatin, 70 mg/m2 IV over 1hr, Day2 Pegylated G-CSF, 6mg SC, Day 3 every 2 weeks




Primary Outcome Measures :
  1. Rate of pathologic complete response (pCR rate) [ Time Frame: From date of enrollment until curative intended surgical treatment, assess up to 2 years ]
    No residual tumor (ypT0N0) in surgical specimen


Secondary Outcome Measures :
  1. Rate of pathologic response [ Time Frame: From date of enrollment until curative intended surgical treatment, assess up to 2 years ]
    No residual tumor (ypT0N0) and partial response (ypTisN0) in surgical specimen

  2. Overall survival (OS) [ Time Frame: From date of enrollment until death, assess up to 3 years ]
    Time from enrollment until death from any cause

  3. Event free survival (EFS) [ Time Frame: From date of enrollment until death, assess up to 3 years ]
    Time from enrollment until the earliest occurrence of disease progression in inoperablity, locoregional recurrence, distant metastasis, or death from any cause

  4. Adverse events related with ddMVAC [ Time Frame: From date of enrollment until 8 weeks after last chemotherapy of ddMVAC ]
    Adverse events related with ddMVAC using CTCAE 4.0

  5. Surgical treatment related complication [ Time Frame: From surgical treatment until 60 the days after surgical treatment ]
    Surgical treatment related complication



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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 of bladder.
  2. Locally advanced status for planning surgical treatment (Bladder, confirm muscle invasiveness using TURBT, or cT3-4a and N1-3 using imaging studies)
  3. Age 18 years or older
  4. Eastern Cooperative Oncology Group performance status 0-1
  5. Adequate organ and bone marrow function for cisplatin based chemotherapy

    A. Adequate bone marrow function: Absolute Neutrophil Count (ANC) ≥ 1,500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9 g/dL)

    B. Adequate renal function: creatinine < 1.5 x upper normal limit (UNL) or creatinine clearance(Ccr) using Cockroft and Gault formula ≥ 50 ml/min

    C. Adequate hepatic function: bilirubin < 1.5 x UNL, AST/ALT levels <5.0 x UNL, alkaline phosphatase < 5 x UNL (except in case of bone metastasis without any liver disease)

  6. 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.
  7. 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. Excess of 4 weeks after initial imaging studies. But, allow the patients to enrollment of study if they is reassessed and reconfirm the localized status using subsequent imaging studies. In this case, clinical stage is decided as following imaging studies.
  3. Prior systemic chemotherapy (But prior intravesical chemotherapy was allowed)
  4. Peripheral sensory neuropathy grade 2 or worse according to NCI CTCAE
  5. History of treatment with drugs of another clinical trial within 30 days before enrollment.
  6. 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

    A. Unstable angina, myocardial infarction, uncontrolled arrhythmias, symptomatic angina pectoris, cardiac failure within the previous 6 months

    B. Active infection which would compromise the patients

    C. Liver cirrohosis or chronic active hepatitis

    D. Poor pulmonary function (DLCO ≤ 50% of normal or resting O2 saturation ≤ 90%)

    E. Clinically significant hemoptysis or gastrointestinal bleeding within previous 6 months

    F. Major psychiatric disorders or other inadequate psychiatric problems according to the physicians decision

  7. 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).
  8. 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): NCT04047693


Contacts
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Contact: Kwonoh Park, MD, PhD +82-10-3378-3529 parkkoh@daum.net
Contact: Bora Kim 01194855124@naver.com

Locations
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Korea, Republic of
Pusan National University Yangsan Hospital Recruiting
Yangsan, Gyeongsangnam-do, Korea, Republic of, 50612
Contact: Kwonoh Park, MD, PhD    82+-10-3378-3529    parkkoh@daum.net   
Sponsors and Collaborators
Pusan National University Yangsan Hospital
Investigators
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Principal Investigator: Kwonoh Park, MD, PhD Pusan National University Yangsan Hospital
Publications of Results:
International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011 Jun 1;29(16):2171-7. doi: 10.1200/JCO.2010.32.3139. Epub 2011 Apr 18.

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Responsible Party: Kwonoh Park, MD phD, Professor, clinical research, Pusan National University Yangsan Hospital
ClinicalTrials.gov Identifier: NCT04047693    
Other Study ID Numbers: ddMVAC
First Posted: August 7, 2019    Key Record Dates
Last Update Posted: August 25, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kwonoh Park, MD phD, Pusan National University Yangsan Hospital:
dose dense MVAC
neoadjuvant chemotherapy
Urothelial carcinoma
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms